Abstract
The development of the conceptual cancer hallmarks has deeply changed our understanding of cancer initiation, progression, and metastasis. Moreover, this pivotal effort is a milestone that provided the scientific rationale for developing new cancer biomarkers and anticancer drugs. In ovarian cancer (OC), the ten cancer hallmarks described by Hanahan and Weinberg were investigated in translational studies for prognostic and predictive biomarker discovery. In addition, several interventional clinical trials used these principles to explore the clinical efficacy of several chemotherapeutic and targeted agents such as antiangiogenics and PARP inhibitors. Promisingly, survival outcomes in women with OC were improved with the arrival of novel single agents and combinatorial approaches. In this chapter, the clinical impact of genetics, biomarkers, and therapy in OC is reviewed based on the hallmarks of cancer. We particularly present a special emphasis on druggable targets investigated in phase II/III clinical trials for OC.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abdel-Rahman O, ElHalawani H, Ahmed H (2016) Doublet BRAF/MEK inhibition versus single-agent BRAF inhibition in the management of BRAF-mutant advanced melanoma, biological rationale and meta-analysis of published data. Clin Transl Oncol 18(8):848–858. https://doi.org/10.1007/s12094-015-1438-0
Abed MN, Abdullah MI, Richardson A (2016) Antagonism of Bcl-XL is necessary for synergy between carboplatin and BH3 mimetics in ovarian cancer cells. J Ovarian Res 9:25. https://doi.org/10.1186/s13048-016-0234-y
Adler E, Mhawech-Fauceglia P, Gayther SA, Lawrenson K (2015) PAX8 expression in ovarian surface epithelial cells. Hum Pathol 46(7):948–956
Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR (2012) OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30(17):2039–2045. https://doi.org/10.1200/JCO.2012.42.0505
Aguilera A, García-Muse T (2013) Causes of genome instability. Annu Rev Genet 47:1–32. https://doi.org/10.1146/annurev-genet-111212-133232
Ahmed N, Thompson EW, Quinn MA (2007) Epithelial-mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas: an exception to the norm. J Cell Physiol 213(3):581–588
Ahn JH, Kim TJ, Lee JH, Choi JH (2017) Mutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells. Sci Rep 7(1):9076. https://doi.org/10.1038/s41598-017-08880-4
Almutairi AR, Alkhatib N, Martin J, Babiker HM, Garland LL, McBride A, Abraham I (2019) Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: a Bayesian network meta-analysis. Crit Rev Oncol Hematol 142:16–25. https://doi.org/10.1016/j.critrevonc.2019.07.004
Andrade RC, Dos Santos AC, de Aguirre Neto JC et al (2017) TP53 and CDKN1A mutation analysis in families with Li-Fraumeni and Li-Fraumeni like syndromes. Fam Cancer 16(2):243–248. https://doi.org/10.1007/s10689-016-9935-z
André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr, KEYNOTE-177 Investigators (2020) Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med 383(23):2207–2218. https://doi.org/10.1056/NEJMoa2017699
Apte RS, Chen DS, Ferrara N (2019) VEGF in signaling and disease: beyond discovery and development. Cell 176(6):1248–1264. https://doi.org/10.1016/j.cell.2019.01.021
Armstrong DK, White AJ, Weil SC et al (2013) Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer. Gynecol Oncol 129(3):452–458. https://doi.org/10.1016/j.ygyno.2013.03.002
Arteaga CL, Engelman JA (2014) ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell 25(3):282–303
Ashaie MA, Chowdhury EH (2016) Cadherins: the superfamily critically involved in breast cancer. Curr Pharm Des 22(5):616–638
Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ (2017) From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat Rev Drug Discov 16(4):273–284. https://doi.org/10.1038/nrd.2016.253
Assaraf YG, Leamon CP, Reddy JA (2014) The folate receptor as a rational therapeutic target for personalized cancer treatment. Drug Resist Updat 17(4–6):89–95. https://doi.org/10.1016/j.drup.2014.10.002
Aubrey BJ, Strasser A, Kelly GL (2016) Tumor-suppressor functions of the TP53 pathway. Cold Spring Harb Perspect Med 6(5):a026062. https://doi.org/10.1101/cshperspect.a026062
Au-Yeung G, Lang F, Azar WJ et al (2016) Selective targeting of cyclin E1-amplified high-grade serous ovarian cancer by cyclin-dependent kinase 2 and AKT inhibition. Clin Cancer Res 23(7):1862–1874
Ayhan A, Kuhn E, Wu RC et al (2017) CCNE1 copy-number gain and overexpression identify ovarian clear cell carcinoma with a poor prognosis. Mod Pathol 30(2):297–303. https://doi.org/10.1038/modpathol.2016.160
Aziz AUR, Farid S, Qin K, Wang H, Liu B (2018a) PIM kinases and their relevance to the PI3K/AKT/mTOR pathway in the regulation of ovarian cancer. Biomolecules 8(1):7. https://doi.org/10.3390/biom8010007
Aziz D, Etemadmoghadam D, Caldon CE et al (2018b) 19q12 amplified and non-amplified subsets of high grade serous ovarian cancer with overexpression of cyclin E1 differ in their molecular drivers and clinical outcomes. Gynecol Oncol 151(2):327–336. https://doi.org/10.1016/j.ygyno.2018.08.039
Bahar-Shany K, Brand H, Sapoznik S et al (2014) Exposure of fallopian tube epithelium to follicular fluid mimics carcinogenic changes in precursor lesions of serous papillary carcinoma. Gynecol Oncol 132(2):322–327. https://doi.org/10.1016/j.ygyno.2013.12.015
Bakkar RM, Xie SS, Urbauer DL et al (2015) Intact PTEN expression by immunohistochemistry is associated with decreased survival in advanced stage ovarian/primary peritoneal high-grade serous carcinoma. Int J Gynecol Pathol 34(6):497–506. https://doi.org/10.1097/PGP.0000000000000205
Bär C, Thum T (2017) Changing direction: from therapeutic telomerase inhibition to activation? Circ Res 120(9):1393–1395. https://doi.org/10.1161/CIRCRESAHA.116.310316
Barbolina MV (2018) Molecular mechanisms regulating organ-specific metastases in epithelial ovarian carcinoma. Cancers (Basel) 10(11):444. https://doi.org/10.3390/cancers10110444
Battista MJ, Cotarelo C, Jakobi S et al (2014) Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients. J Cancer Res Clin Oncol 140(7):1097–1102. https://doi.org/10.1007/s00432-014-1672-9
Baumann K, Pfisterer J, Wimberger P et al (2011) Intraperitoneal treatment with the trifunctional bispecific antibody Catumaxomab in patients with platinum-resistant epithelial ovarian cancer: a phase IIa study of the AGO Study Group. Gynecol Oncol 123(1):27–32. https://doi.org/10.1016/j.ygyno.2011.06.004
Bayard Q, Meunier L, Peneau C et al (2018) Cyclin A2/E1 activation defines a hepatocellular carcinoma subclass with a rearrangement signature of replication stress. Nat Commun 9(1):5235. https://doi.org/10.1038/s41467-018-07552-9
Beck A, Goetsch L, Dumontet C et al (2017) Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov 16(5):315–337. https://doi.org/10.1038/nrd.2016.268
Bedard PL, Tabernero J, Janku F et al (2015) A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumors. Clin Cancer Res 21(4):730–738. https://doi.org/10.1158/1078-0432.CCR-14-1814
Behbakht K, Sill MW, Darcy KM et al (2011) Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study. Gynecol Oncol 123(1):19–26
Bellone S, Siegel ER, Cocco E et al (2009) Overexpression of epithelial cell adhesion molecule in primary, metastatic, and recurrent/chemotherapy-resistant epithelial ovarian cancer: implications for epithelial cell adhesion molecule-specific immunotherapy. Int J Gynecol Cancer 19(5):860–866. https://doi.org/10.1111/IGC.0b013e3181a8331f
Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, Rimm DL, Liu Y, Ratner ES, Schwartz PE, Santin AD (2018) Exceptional response to pembrolizumab in a metastatic, chemotherapy/radiation-resistant ovarian cancer patient harboring a PD-L1-genetic rearrangement. Clin Cancer Res 24(14):3282–3291. https://doi.org/10.1158/1078-0432.CCR-17-1805
Berek JS, Edwards RP, Parker LP et al (2014) Catumaxomab for the treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer: a phase II study. Int J Gynecol Cancer 24(9):1583–1589. https://doi.org/10.1097/IGC.0000000000000286
Bergamini A, Ferrero S, Leone Roberti Maggiore U et al (2016) Folate receptor alpha antagonists in preclinical and early stage clinical development for the treatment of epithelial ovarian cancer. Expert Opin Investig Drugs 25(12):1405–1412
Bernardini MQ, Baba T, Lee PS et al (2010) Expression signatures of TP53 mutations in serous ovarian cancers. BMC Cancer 10:237. https://doi.org/10.1186/1471-2407-10-237
Bialucha CU, Collins SD, Li X et al (2017) Discovery and optimization of HKT288, a cadherin-6-targeting ADC for the treatment of ovarian and renal cancers. Cancer Discov 7(9):1030–1045. https://doi.org/10.1158/2159-8290.CD-16-1414
Bielski CM, Zehir A, Penson AV et al (2018) Genome doubling shapes the evolution and prognosis of advanced cancers. Nat Genet 50(8):1189–1195
Bilanges B, Posor Y, Vanhaesebroeck B (2019) PI3K isoforms in cell signalling and vesicle trafficking. Nat Rev Mol Cell Biol 20(9):515–534. https://doi.org/10.1038/s41580-019-0129-z
Boers-Sonderen MJ, de Geus-Oei LF, Desar IM et al (2014) Temsirolimus and pegylated liposomal doxorubicin (PLD) combination therapy in breast, endometrial, and ovarian cancer: phase Ib results and prediction of clinical outcome with FDG-PET/CT. Target Oncol 9(4):339–347. https://doi.org/10.1007/s11523-014-0309-x
Bonnefond ML, Lambert B, Giffard F, Abeilard E, Brotin E, Louis MH, Gueye MS, Gauduchon P, Poulain L, N’Diaye M (2015) Calcium signals inhibition sensitizes ovarian carcinoma cells to anti-Bcl-xL strategies through Mcl-1 down-regulation. Apoptosis 20(4):535–550. https://doi.org/10.1007/s10495-015-1095-3
Bouaoun L, Sonkin D, Ardin M et al (2016) TP53 variations in human cancers: new lessons from the IARC TP53 database and genomics data. Hum Mutat 37(9):865–876. https://doi.org/10.1002/humu.23035
Brachet PE, Fabbro M, Leary A et al (2017) A gineco phase II study of navitoclax (abt 263) in women with platinum resistant/refractory recurrent ovarian cancer (roc). Ann Oncol 28. https://doi.org/10.1093/annonc/mdy285.179
Braem MG, Schouten LJ, Peeters PH et al (2011) Genetic susceptibility to sporadic ovarian cancer: a systematic review. Biochim Biophys Acta 1816(2):132–146. https://doi.org/10.1016/j.bbcan.2011.05.002
Braicu EI, Luketina H, Richter R, Cacsire Castillo-Tong D, Lambrechts S, Mahner S, Concin N, Mentze M, Zeillinger R, Vergote I, Sehouli J (2014) HIF1α is an independent prognostic factor for overall survival in advanced primary epithelial ovarian cancer – a study of the OVCAD Consortium. Onco Targets Ther 7:1563–1569. https://doi.org/10.2147/OTT.S65373
Bregar AJ, Growdon WB (2016) Emerging strategies for targeting PI3K in gynecologic cancer. Gynecol Oncol 140(2):333–344. https://doi.org/10.1016/j.ygyno.2015.09.083
Brosh R, Rotter V (2009) When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer 9(10):701–713. https://doi.org/10.1038/nrc2693
Brotin E, Meryet-Figuière M, Simonin K, Duval RE, Villedieu M, Leroy-Dudal J, Saison-Behmoaras E, Gauduchon P, Denoyelle C, Poulain L (2010) Bcl-XL and MCL-1 constitute pertinent targets in ovarian carcinoma and their concomitant inhibition is sufficient to induce apoptosis. Int J Cancer 126(4):885–895. https://doi.org/10.1002/ijc.24787
Brüser L, Bogdan S (2017) Adherens junctions on the move-membrane trafficking of e-cadherin. Cold Spring Harb Perspect Biol 9(3):a029140. https://doi.org/10.1101/cshperspect.a029140
Buderath P, Mairinger F, Mairinger E, Böhm K, Mach P, Schmid KW, Kimmig R, Kasimir-Bauer S, Bankfalvi A, Westerwick D, Hager T (2019) Prognostic significance of PD-1 and PD-L1 positive tumor-infiltrating immune cells in ovarian carcinoma. Int J Gynecol Cancer 29(9):1389–1395. https://doi.org/10.1136/ijgc-2019-000609
Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX, Gynecologic Oncology Group (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365(26):2473–2483. https://doi.org/10.1056/NEJMoa1104390
Cai J, Xu L, Tang H et al (2014) The role of the PTEN/PI3K/Akt pathway on prognosis in epithelial ovarian cancer: a meta-analysis. Oncologist 19(5):528–535
Cai L, Michelakos T, Ferrone CR et al (2017) Expression status of folate receptor alpha is a predictor of survival in pancreatic ductal adenocarcinoma. Oncotarget 8(23):37646–37656
Cancer Genome Atlas Research Network (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474(7353):609–615. https://doi.org/10.1038/nature10166
Cantuaria G, Fagotti A, Ferrandina G, Magalhaes A, Nadji M, Angioli R, Penalver M, Mancuso S, Scambia G (2001) GLUT-1 expression in ovarian carcinoma: association with survival and response to chemotherapy. Cancer 92(5):1144–1150. https://doi.org/10.1002/1097-0142(20010901)92:5<1144::aid-cncr1432>3.0.co;2-t
Caramel J, Ligier M, Puisieux A (2018) Pleiotropic roles for ZEB1 in cancer. Cancer Res 78(1):30–35. https://doi.org/10.1158/0008-5472.CAN-17-2476
Carneiro BA, El-Deiry WS (2020) Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol 17(7):395–417. https://doi.org/10.1038/s41571-020-0341-y
Castro MP, Whitcomb BP, Zajchowski DA, Coleman RL (2015) Successful use of next generation genomic sequencing (NGS)-directed therapy of clear cell carcinoma of the ovary (CCCO) with trametinib and metformin in a patient with chemotherapy-refractory disease. Gynecol Oncol Res Pract 2:4. https://doi.org/10.1186/s40661-015-0013-2
Chen J, Wang L, Matyunina LV, Hill CG, McDonald JF (2011) Overexpression of miR-429 induces mesenchymal-to-epithelial transition (MET) in metastatic ovarian cancer cells. Gynecol Oncol 121(1):200–205. https://doi.org/10.1016/j.ygyno.2010.12.339
Chen YL, Chang MC, Huang CY et al (2012) Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response. Mol Oncol 6(3):360–369
Chen C, Li J, Yao G, Chambers SK, Zheng W (2013) Tubal origin of ovarian low-grade serous carcinoma. Am J Clin Exp Obstet Gynecol 1(1):13–36
Chen Y, Wang DD, Wu YP et al (2017) MDM2 promotes epithelial-mesenchymal transition and metastasis of ovarian cancer SKOV3 cells. Br J Cancer 117(8):1192–1201
Chen H, Molberg K, Strickland AL, Castrillon DH, Carrick K, Jiang Q, Niu S, Rivera-Colon G, Gwin K, Hinson S, Lea J, Miller DS, Zheng W, Lucas E (2020) PD-L1 expression and CD8+ tumor-infiltrating lymphocytes in different types of tubo-ovarian carcinoma and their prognostic value in high-grade serous carcinoma. Am J Surg Pathol 44(8):1050–1060. https://doi.org/10.1097/PAS.0000000000001503
Cheung LW, Leung PC, Wong AS (2010) Cadherin switching and activation of p120 catenin signaling are mediators of gonadotropin-releasing hormone to promote tumor cell migration and invasion in ovarian cancer. Oncogene 29(16):2427–2440. https://doi.org/10.1038/onc.2009.523
Chien J, Sicotte H, Fan JB et al (2015) TP53 mutations, tetraploidy and homologous recombination repair defects in early stage high-grade serous ovarian cancer. Nucleic Acids Res 43(14):6945–6958
Chmelarova M, Baranova I, Ruszova E et al (2018) Importance of cadherins methylation in ovarian cancer: a next generation sequencing approach. Pathol Oncol Res. https://doi.org/10.1007/s12253-018-0500-y
Cho H, Lee YS, Kim J, Chung JY, Kim JH (2013) Overexpression of glucose transporter-1 (GLUT-1) predicts poor prognosis in epithelial ovarian cancer. Cancer Invest 31(9):607–615. https://doi.org/10.3109/07357907.2013.849722
Chui MH, Wang Y, Wu RC et al (2014) Loss of ALDH1A1 expression is an early event in the pathogenesis of ovarian high-grade serous carcinoma. Mod Pathol 28(3):437–445
Cibula D, Zikan M, Dusek L et al (2011) Oral contraceptives and risk of ovarian and breast cancers in BRCA mutation carriers: a meta-analysis. Expert Rev Anticancer Ther 11(8):1197–1207. https://doi.org/10.1586/era.11.38
Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O’Malley DM, Davidson SA, Rubin SC, Di Silvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS (2017a) Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18(6):779–791. https://doi.org/10.1016/S1470-2045(17)30279-6
Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O’Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA, ARIEL3 Investigators (2017b) Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebocontrolled, phase 3 trial. Lancet 390(10106):1949–1961. https://doi.org/10.1016/S01406736(17)32440-6. Epub 2017 Sep 12. Erratum in: Lancet. 2017 Oct 28;390(10106):1948
Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, Di Silvestro PA, Morgan MA, Nam JH, Leath CA III, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA (2019) Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med 381(25):2403–2415. https://doi.org/10.1056/NEJMoa1909707
Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Doll R, et al. (2008) Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet 371(9609):303–314. https://doi.org/10.1016/S0140-6736(08)60167-1
Collins C, Nelson WJ (2015) Running with neighbors: coordinating cell migration and cell-cell adhesion. Curr Opin Cell Biol 36:62–70
Colon-Otero G, Weroha SJ, Foster NR et al (2017) Phase 2 trial of everolimus and letrozole in relapsed estrogen receptor-positive high-grade ovarian cancers. Gynecol Oncol 146(1):64–68. https://doi.org/10.1016/j.ygyno.2017.04.020
Cormedi MCV, Van Allen EM, Colli LM (2020) Predicting immunotherapy response through genomics. Curr Opin Genet Dev 66:1–9. https://doi.org/10.1016/j.gde.2020.11.004
Cossa G, Lanzi C, Cassinelli G et al (2014) Differential outcome of MEK1/2 inhibitor-platinum combinations in platinum-sensitive and -resistant ovarian carcinoma cells. Cancer Lett 347(2):212–224. https://doi.org/10.1016/j.canlet.2014.02.016
Cui Y, Qin L, Tian D et al (2018) ZEB1 promotes chemoresistance to cisplatin in ovarian cancer cells by suppressing SLC3A2. Chemotherapy 63(5):262–271. https://doi.org/10.1159/000493864
Damen MPF, van Rheenen J, Scheele CLGJ (2020) Targeting dormant tumor cells to prevent cancer recurrence. FEBS J. https://doi.org/10.1111/febs.15626
De Luca A, Maiello MR, D’Alessio A et al (2012) The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets 16(Suppl 2):S17–S27. https://doi.org/10.1517/14728222.2011.639361
De Palma M, Hanahan D (2012) The biology of personalized cancer medicine: facing individual complexities underlying hallmark capabilities. Mol Oncol 6(2):111–127. https://doi.org/10.1016/j.molonc.2012.01.011
De Picciotto N, Cacheux W, Roth A et al (2016) Ovarian cancer: status of homologous recombination pathway as a predictor of drug response. Crit Rev Oncol 101:50–59. https://doi.org/10.1016/j.critrevonc.2016.02.014
de Wit S, Rossi E, Weber S et al (2019) Single tube liquid biopsy for advanced non-small cell lung cancer. Int J Cancer 144(12):3127–3137. https://doi.org/10.1002/ijc.32056
DeFazio A, Moujaber T, Etemadmoghadam D, Kennedy C, Chiew YE, Balleine RL et al (2016) Abstract A25: brafv600E mutations in serous ovarian cancer and response to the BRAF inhibitor, dabrafenib. Clin Cancer Res 22:a25. https://doi.org/10.1158/1557-3265.OVCA15-A25
Della Pepa C, Tonini G, Santini D et al (2015) Low Grade Serous Ovarian Carcinoma: from the molecular characterization to the best therapeutic strategy. Cancer Treat Rev 41(2):136–143. https://doi.org/10.1016/j.ctrv.2014.12.003
Demir L, Yigit S, Sadullahoglu C et al (2014) Hormone receptor, HER2/NEU and EGFR expression in ovarian carcinoma–is here a prognostic phenotype? Asian Pac J Cancer Prev 15(22):9739–9745
Deng L, Feng DQ, Ling B (2020) Cyclooxygenase-2 promotes ovarian cancer cell migration and cisplatin resistance via regulating epithelial mesenchymal transition. J Zhejiang Univ Sci B 21(4):315–326. https://doi.org/10.1631/jzus.B1900445
Despierre E et al (2015) Epidermal growth factor receptor (EGFR) pathway biomarkers in the randomized phase III trial of erlotinib versus observation in ovarian cancer patients with no evidence of disease progression after first-line platinum-based chemotherapy. Target Oncol 10(4):583–596
Dhillon S (2016) Dabrafenib plus trametinib: a review in advanced melanoma with a BRAF (V600) mutation. Target Oncol 11(3):417–428. https://doi.org/10.1007/s11523-016-0443-8
Di Fiore R, D’Anneo A, Tesoriere G et al (2013) RB1 in cancer: different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis. J Cell Physiol 228(8):1676–1687. https://doi.org/10.1002/jcp.24329
Diakos CI, Charles KA, McMillan DC et al (2014) Cancer-related inflammation and treatment effectiveness. Lancet Oncol 15(11):e493–e503. https://doi.org/10.1016/S1470-2045(14)70263-3
Dick FA, Rubin SM (2013) Molecular mechanisms underlying RB protein function. Nat Rev Mol Cell Biol 14(5):297–306
Disis ML, Taylor MH, Kelly K et al (2019) Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: phase 1b results from the JAVELIN solid tumor trial. JAMA Oncol 5(3):393–401. https://doi.org/10.1001/jamaoncol.2018.6258
Dong D, Dong Y, Fu J, Lu S, Yuan C, Xia M, Sun L (2020) Bcl2 inhibitor ABT737 reverses the Warburg effect via the Sirt3-HIF1α axis to promote oxidative stress-induced apoptosis in ovarian cancer cells. Life Sci 255:117846. https://doi.org/10.1016/j.lfs.2020.117846
Drew Y, Penson RT, O’Malley DM et al (2020) Phase II study of olaparib (O) plus durvalumab (D) and bevacizumab (B) (MEDIOLA): initial results in patients (pts) with non-germline BRCA-mutated (non-gBRCAm) platinum sensitive relapsed (PSR) ovarian cancer (OC) [ESMO abstract 814MO]. Ann Oncol 31(Suppl 4):S615–S616
du Bois A, Floquet A, Kim JW, Rau J, del Campo JM, Friedlander M, Pignata S, Fujiwara K, Vergote I, Colombo N, Mirza MR, Monk BJ, Kimmig R, Ray-Coquard I, Zang R, Diaz-Padilla I, Baumann KH, Mouret-Reynier MA, Kim JH, Kurzeder C, Lesoin A, Vasey P, Marth C, Canzler U, Scambia G, Shimada M, Calvert P, Pujade-Lauraine E, Kim BG, Herzog TJ, Mitrica I, Schade-Brittinger C, Wang Q, Crescenzo R, Harter P (2014) Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol 32(30):3374–3382. https://doi.org/10.1200/JCO.2014.55.7348
du Bois A, Kristensen G, Ray-Coquard I, Reuss A, Pignata S, Colombo N, Denison U, Vergote I, Del Campo JM, Ottevanger P, Heubner M, Minarik T, Sevin E, de Gregorio N, Bidziński M, Pfisterer J, Malander S, Hilpert F, Mirza MR, Scambia G, Meier W, Nicoletto MO, Bjørge L, Lortholary A, Sailer MO, Merger M, Harter P, AGO Study Group led Gynecologic Cancer Intergroup/European Network of Gynaecologic Oncology Trials Groups Intergroup Consortium (2016) Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 17(1):78–89. https://doi.org/10.1016/S1470-2045(15)00366-6
Du J, Sun B, Zhao X, Gu Q, Dong X, Mo J, Sun T, Wang J, Sun R, Liu Y (2014) Hypoxia promotes vasculogenic mimicry formation by inducing epithelial-mesenchymal transition in ovarian carcinoma. Gynecol Oncol 133(3):575–583. https://doi.org/10.1016/j.ygyno.2014.02.034
Du ZH, Bi FF, Wang L, Yang Q (2018) Next-generation sequencing unravels extensive genetic alteration in recurrent ovarian cancer and unique genetic changes in drug-resistant recurrent ovarian cancer. Mol Genet Genomic Med 6(4):638–647. https://doi.org/10.1002/mgg3.414
Duska LR, Krasner CN, O’Malley DM, Hays JL, Modesitt SC, Mathews CA, Moore KN, Thaker PH, Miller A, Purdy C, Zamboni WC, Lucas AT, Supko JG, Schilder RJ (2020) A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer. Gynecol Oncol. S0090-8258(20)34228-1. https://doi.org/10.1016/j.ygyno.2020.12.025
Ebnet K, Kummer D, Steinbacher T et al (2018) Regulation of cell polarity by cell adhesion receptors. Semin Cell Dev Biol 81:2–12. https://doi.org/10.1016/j.semcdb.2017.07.032
El Bairi K, Amrani M, Maleb A (2020) Gut microbiota, next-generation sequencing, immune-checkpoint inhibitors, and colorectal cancer: how hot is the link? In: El Bairi K (ed) Illuminating colorectal cancer genomics by next-generation sequencing. Springer, Cham. https://doi.org/10.1007/978-3-030-53821-7_5
El Bairi K, Al Jarroudi O, Afqir S (2021) Revisiting antibody-drug conjugates and their predictive biomarkers in platinum-resistant ovarian cancer. Semin Cancer Biol. S1044-579X(21)00081-X. https://doi.org/10.1016/j.semcancer.2021.03.031
Elyashiv O, Ledermann J, Parmar G, Farrelly L, Counsell N, Feeney A, El-Khouly F, Macdonald I, Neto A, Arthur-Darkwa E, Burnett E, Jayson GC, Mileshkin L, Gourley C, Nicum S (2021) ICON 9-an international phase III randomized study to evaluate the efficacy of maintenance therapy with olaparib and cediranib or olaparib alone in patients with relapsed platinum-sensitive ovarian cancer following a response to platinum-based chemotherapy. Int J Gynecol Cancer 31(1):134–138. https://doi.org/10.1136/ijgc-2020-002073
Emons G, Kurzeder C, Schmalfeldt B et al (2016) Temsirolimus in women with platinum-refractory/resistant ovarian cancer or advanced/recurrent endometrial carcinoma. A phase II study of the AGO-study group (AGO-GYN8). Gynecol Oncol 140(3):450–456. https://doi.org/10.1016/j.ygyno.2015.12.025
Endo H, Inoue M (2019) Dormancy in cancer. Cancer Sci 110(2):474–480. https://doi.org/10.1111/cas.13917
Etemadmoghadam D, de Fazio A, Beroukhim R, Mermel C, George J, Getz G, Tothill R, Okamoto A, Raeder MB, Harnett P, Lade S, Akslen LA, Tinker AV, Locandro B, Alsop K, Chiew YE, Traficante N, Fereday S, Johnson D, Fox S, Sellers W, Urashima M, Salvesen HB, Meyerson M, Bowtell D, AOCS Study Group (2009) Integrated genome-wide DNA copy number and expression analysis identifies distinct mechanisms of primary chemoresistance in ovarian carcinomas. Clin Cancer Res 15(4):1417–1427. https://doi.org/10.1158/1078-0432.CCR-08-1564
Etemadmoghadam D, George J, Cowin PA et al (2010) Amplicon-dependent CCNE1 expression is critical for clonogenic survival after cisplatin treatment and is correlated with 20q11 gain in ovarian cancer. PLoS One 5(11):e15498. https://doi.org/10.1371/journal.pone.0015498
Etemadmoghadam D, Au-Yeung G, Wall M et al (2013a) Resistance to CDK2 inhibitors is associated with selection of polyploid cells in CCNE1-amplified ovarian cancer. Clin Cancer Res 19(21):5960–5971. https://doi.org/10.1158/1078-0432.CCR-13-1337
Etemadmoghadam D, Weir BA, Au-Yeung G et al (2013b) Synthetic lethality between CCNE1 amplification and loss of BRCA1. Proc Natl Acad Sci U S A 110(48):19489–19494
Fardi M, Alivand M, Baradaran B, Farshdousti Hagh M, Solali S (2019) The crucial role of ZEB2: from development to epithelial-to-mesenchymal transition and cancer complexity. J Cell Physiol. https://doi.org/10.1002/jcp.28277
Färkkilä A, Gulhan DC, Casado J et al (2020) Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer [published correction appears in Nat Commun 2020;11(1):2543]. Nat Commun 11(1):1459. https://doi.org/10.1038/s41467-020-15315-8
Farley J, Brady WE, Vathipadiekal V et al (2013) Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol 14(2):134–140
Fernández ML, DiMattia GE, Dawson A et al (2016) Differences in MEK inhibitor efficacy in molecularly characterized low-grade serous ovarian cancer cell lines. Am J Cancer Res 6(10):2235–2251
Fernandez ML, Dawson A, Hoenisch J et al (2019) Markers of MEK inhibitor resistance in low-grade serous ovarian cancer: EGFR is a potential therapeutic target. Cancer Cell Int 19:10. https://doi.org/10.1186/s12935-019-0725-1
Ferreira AR, Felgueiras J, Fardilha M (2015) Signaling pathways in anchoring junctions of epithelial cells: cell-to-cell and cell-to-extracellular matrix interactions. J Recept Signal Transduct Res 35(1):67–75. https://doi.org/10.3109/10799893.2014.931426
Flesken-Nikitin A, Hwang CI, Cheng CY, Michurina TV, Enikolopov G, Nikitin AY (2013) Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature 495(7440):241–245
Florent R, Weiswald LB, Lambert B, Brotin E, Abeilard E, Louis MH, Babin G, Poulain L, N’Diaye M (2020a) Bim, Puma and Noxa upregulation by Naftopidil sensitizes ovarian cancer to the BH3-mimetic ABT-737 and the MEK inhibitor Trametinib. Cell Death Dis 11(5):380. https://doi.org/10.1038/s41419-020-2588-8
Florent R, Poulain L, N’Diaye M (2020b) Drug repositioning of the α1-adrenergic receptor antagonist naftopidil: a potential new anti-cancer drug? Int J Mol Sci 21(15):5339. https://doi.org/10.3390/ijms21155339
Fortner RT, Poole EM, Wentzensen NA et al (2018) Ovarian cancer risk factors by tumor aggressiveness: an analysis from the Ovarian Cancer Cohort Consortium. Int J Cancer. https://doi.org/10.1002/ijc.32075
Fotiadis D, Kanai Y, Palacín M (2013) The SLC3 and SLC7 families of amino acid transporters. Mol Aspects Med 34(2–3):139–158. https://doi.org/10.1016/j.mam.2012.10.007
Fowler M (2020) Mirvetuximab soravtansine combination yields encouraging response rates in ovarian cancer. Oncology (Williston Park) 34(7):250
Frampton JE (2012) Catumaxomab: in malignant ascites. Drugs 72(10):1399–1410. https://doi.org/10.2165/11209040-000000000-00000
Franzese E, Diana A, Centonze S et al (2020) PARP inhibitors in first-line therapy of ovarian cancer: are there any doubts? Front Oncol 10:782. https://doi.org/10.3389/fonc.2020.00782
Friese C, Harbst K, Borch TH, Westergaard MCW, Pedersen M, Kverneland A, Jönsson G, Donia M, Svane IM, Met Ö (2020) CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer. Sci Rep 10(1):3914. https://doi.org/10.1038/s41598-020-60738-4
Fruman DA, Rommel C (2014) PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov 13(2):140–156
Fu S, Hennessy BT, Ng CS et al (2012) Perifosine plus docetaxel in patients with platinum and taxane resistant or refractory high-grade epithelial ovarian cancer. Gynecol Oncol 126(1):47–53. https://doi.org/10.1016/j.ygyno.2012.04.006
Fumet JD, Truntzer C, Yarchoan M, Ghiringhelli F (2020) Tumour mutational burden as a biomarker for immunotherapy: current data and emerging concepts. Eur J Cancer 131:40–50. https://doi.org/10.1016/j.ejca.2020.02.038
Galluzzi L, Kepp O, Chan FK, Kroemer G (2017) Necroptosis: mechanisms and relevance to disease. Annu Rev Pathol 12:103–130. https://doi.org/10.1146/annurev-pathol-052016-100247
Galluzzi L, Vitale I, Aaronson SA et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25(3):486–541. https://doi.org/10.1038/s41418-017-0012-4
Gao H, Li X, Zhan G et al (2019) Long noncoding RNA MAGI1-IT1 promoted invasion and metastasis of epithelial ovarian cancer via the miR-200a/ZEB axis. Cell Cycle 18(12):1393–1406. https://doi.org/10.1080/15384101.2019.1618121
Garsed DW, Alsop K, Fereday S et al (2018) Homologous recombination DNA repair pathway disruption and retinoblastoma protein loss are associated with exceptional survival in high-grade serous ovarian cancer. Clin Cancer Res 24(3):569–580. https://doi.org/10.1158/1078-0432.CCR-17-1621
Gershenson DM, Sun CC, Wong KK (2015) Impact of mutational status on survival in low-grade serous carcinoma of the ovary or peritoneum. Br J Cancer 113(9):1254–1258
Gewinner C, Wang ZC, Richardson A et al (2009) Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell 16(2):115–125
Gheldof A, Berx G (2013) Cadherins and epithelial-to-mesenchymal transition. Prog Mol Biol Transl Sci 116:317–336. https://doi.org/10.1016/B978-0-12-394311-8.00014-5
Ghezelayagh TS, Pennington KP, Norquist BM et al (2020) Characterizing TP53 mutations in ovarian carcinomas with and without concurrent BRCA1 or BRCA2 mutations. Gynecol Oncol. https://doi.org/10.1016/j.ygyno.2020.12.007
Ghigo A, Morello F, Perino A et al (2012) Phosphoinositide 3-kinases in health and disease. Subcell Biochem 58:183–213. https://doi.org/10.1007/978-94-007-3012-0_6
Ginter PS, McIntire PJ, Cui X et al (2017) Folate receptor alpha expression is associated with increased risk of recurrence in triple-negative breast cancer. Clin Breast Cancer 17(7):544–549. https://doi.org/10.1016/j.clbc.2017.03.007
Gloushankova NA, Rubtsova SN, Zhitnyak IY (2017) Cadherin-mediated cell-cell interactions in normal and cancer cells. Tissue Barriers 5(3):e1356900
González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O’Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ, PRIMA/ENGOT-OV26/GOG-3012 Investigators (2019) Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 381(25):2391–2402. https://doi.org/10.1056/NEJMoa1910962
González-Martín A, Sanchez Lorenzo L, Colombo N, dePont Christensen R, Heitz F, Meirovitz M, Selle F, van Gorp T, Alvarez N, Sanchez J, Marqués C (2020) A phase III, randomized, double blinded trial of platinum based chemotherapy with or without atezolizumab followed by niraparib maintenance with or without atezolizumab in patients with recurrent ovarian, tubal, or peritoneal cancer and platinum treatment free interval of more than 6 months: engot-Ov41/GEICO 69-O/ANITA Trial. Int J Gynecol Cancer. https://doi.org/10.1136/ijgc-2020-001633
Grisham RN, Iyer G, Garg K et al (2012) BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer. Cancer 119(3):548–554
Grisham RN, Moore KN, Gordon MS et al (2018) Phase Ib study of binimetinib with paclitaxel in patients with platinum-resistant ovarian cancer: final results, potential biomarkers, and extreme responders. Clin Cancer Res 24(22):5525–5533. https://doi.org/10.1158/1078-0432.CCR-18-0494
Grover PK, Cummins AG, Price TJ, Roberts-Thomson IC, Hardingham JE (2014) Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research. Ann Oncol 25(8):1506–1516. https://doi.org/10.1093/annonc/mdu018
Gruosso T, Garnier C, Abelanet S et al (2015) MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas. Nat Commun 6:8583. https://doi.org/10.1038/ncomms9583
Gugnoni M, Sancisi V, Gandolfi G et al (2017) Cadherin-6 promotes EMT and cancer metastasis by restraining autophagy. Oncogene 36(5):667–677. https://doi.org/10.1038/onc.2016.237
Guha T, Malkin D (2017) Inherited TP53 mutations and the Li-Fraumeni syndrome. Cold Spring Harb Perspect Med 7(4). pii: a026187. https://doi.org/10.1101/cshperspect.a026187
Gupta R, Cristea M, Frankel P, Ruel C, Chen C, Wang Y, Morgan R, Leong L, Chow W, Koczywas M, Koehler S, Lim D, Luu T, Martel C, McNamara M, Somlo G, Twardowski P, Yen Y, Idorenyi A, Raechelle T, Carroll M, Chung V (2019) Randomized trial of oral cyclophosphamide versus oral cyclophosphamide with celecoxib for recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer. Cancer Treat Res Commun 21:100155. https://doi.org/10.1016/j.ctarc.2019.100155
Hainaut P, Pfeifer GP (2016) Somatic TP53 mutations in the era of genome sequencing. Cold Spring Harb Perspect Med 6(11):a026179. https://doi.org/10.1101/cshperspect.a026179
Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, Kanai M, Mori Y, Matsumoto S, Chikuma S, Matsumura N, Abiko K, Baba T, Yamaguchi K, Ueda A, Hosoe Y, Morita S, Yokode M, Shimizu A, Honjo T, Konishi I (2015) Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol 33(34):4015–4022. https://doi.org/10.1200/JCO.2015.62.3397
Han C, Bellone S, Zammataro L, Schwartz PE, Santin AD (2018) Binimetinib (MEK162) in recurrent low-grade serous ovarian cancer resistant to chemotherapy and hormonal treatment. Gynecol Oncol Rep 25:41–44. https://doi.org/10.1016/j.gore.2018.05.011
Hanahan D, Coussens LM (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21(3):309–322. https://doi.org/10.1016/j.ccr.2012.02.022
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70. https://doi.org/10.1016/s0092-8674(00)81683-9
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 14:646–674. https://doi.org/10.1016/j.cell.2011.02.013
Hao J, Yu H, Zhang T, An R, Xue Y (2020) Prognostic impact of tumor-infiltrating lymphocytes in high grade serous ovarian cancer: a systematic review and meta-analysis. Ther Adv Med Oncol 12:1758835920967241. https://doi.org/10.1177/1758835920967241
Hao J, Liu Y, Zhang T, He J, Zhao H, An R, Xue Y (2021) Efficacy and safety of PARP inhibitors in the treatment of advanced ovarian cancer: an updated systematic review and meta-analysis of randomized controlled trials. Crit Rev Oncol Hematol 157:103145. https://doi.org/10.1016/j.critrevonc.2020.103145
Harter P, Pautier P, Van Nieuwenhuysen E, Reuss A, Redondo A, Lindemann K, Kurzeder C, Petru E, Heitz F, Sehouli J, Degregorio N, Wimberger P, Burges A, Cron N, Ledermann J, Lorusso D, Paoletti X, Marme F (2020) Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer – a randomized phase III trial (AGO-OVAR 2.29/ENGOT-ov34). Int J Gynecol Cancer 30(12):1997–2001. https://doi.org/10.1136/ijgc-2020-001572
Hasegawa K, Kagabu M, Mizuno M et al (2017) Phase II basket trial of perifosine monotherapy for recurrent gynecologic cancer with or without PIK3CA mutations. Invest New Drugs 35(6):800–812. https://doi.org/10.1007/s10637-017-0504-6
Havrilesky LJ, Moorman PG, Lowery WJ et al (2013) Oral contraceptive pills as primary prevention for ovarian cancer: a systematic review and meta-analysis. Obstet Gynecol 122(1):139–147. https://doi.org/10.1097/AOG.0b013e318291c235
Hazan RB, Qiao R, Keren R, Badano I, Suyama K (2004) Cadherin switch in tumor progression. Ann N Y Acad Sci 1014:155–163. https://doi.org/10.1196/annals.1294.016
Heiss MM, Murawa P, Koralewski P et al (2010) The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer 127(9):2209–2221. https://doi.org/10.1002/ijc.25423
Herreros-Pomares A, Aguilar-Gallardo C, Calabuig-Fariñas S, Sirera R, Jantus-Lewintre E, Camps C (2018) EpCAM duality becomes this molecule in a new Dr. Jekyll and Mr. Hyde tale. Crit Rev Oncol Hematol 126:52–63. https://doi.org/10.1016/j.critrevonc.2018.03.006
Hew KE, Miller PC, El-Ashry D et al (2015) MAPK activation predicts poor outcome and the MEK inhibitor, selumetinib, reverses antiestrogen resistance in ER-positive high-grade serous ovarian cancer. Clin Cancer Res 22(4):935–947
Høgdall EV, Christensen L, Kjaer SK, Blaakaer J, Christensen IJ, Høgdall CK (2010) Limited prognostic value of tissue protein expression levels of BCl-2 in Danish ovarian cancer patients: from the Danish ‘MALOVA’ ovarian cancer study. APMIS 118(8):557–564. https://doi.org/10.1111/j.1600-0463.2010.02614.x
Hortobagyi GN, Stemmer SM, Burris HA et al (2016) Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 375(18):1738–1748
Huang LN, Wang DS, Chen YQ et al (2012) Meta-analysis for cyclin E in lung cancer survival. Clin Chim Acta 413(7-8):663–668. https://doi.org/10.1016/j.cca.2011.12.020
Huang TB, Yan Y, Guo ZF et al (2014a) Aspirin use and the risk of prostate cancer: a metaanalysis of 24 epidemiologic studies. Int Urol Nephrol 46(9):1715–1728. https://doi.org/10.1007/s11255-014-0703-4
Huang HN, Huang WC, Lin CH et al (2014b) Chromosome 20q13.2 ZNF217 locus amplification correlates with decreased E-cadherin expression in ovarian clear cell carcinoma with PI3K-Akt pathway alterations. Hum Pathol 45(11):2318–2325. https://doi.org/10.1016/j.humpath.2014.07.020
Huang HS, Chu SC, Hsu CF et al (2015) Mutagenic, surviving and tumorigenic effects of follicular fluid in the context of p53 loss: initiation of fimbria carcinogenesis. Carcinogenesis 36(11):1419–1428. https://doi.org/10.1093/carcin/bgv132
Hudson LG, Zeineldin R, Stack MS (2008) Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression. Clin Exp Metastasis 25(6):643–655
Hui G, Meng M (2015) Prognostic value of vascular endothelial growth factor expression in women with ovarian cancer: a meta-analysis. J BUON 20(3):870–878
Hwang WT, Adams SF, Tahirovic E, Hagemann IS, Coukos G (2012) Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol 124(2):192–198. https://doi.org/10.1016/j.ygyno.2011.09.039
Iavarone C, Zervantonakis IK, Selfors LM, Palakurthi S, Liu JF, Drapkin R, Matulonis UA, Hallberg D, Velculescu VE, Leverson JD, Sampath D, Mills GB, Brugge JS (2019) Combined MEK and BCL-2/XL inhibition is effective in high-grade serous ovarian cancer patient-derived xenograft models and BIM levels are predictive of responsiveness. Mol Cancer Ther 18(3):642–655. https://doi.org/10.1158/1535-7163.MCT-18-0413
Icard P, Shulman S, Farhat D, Steyaert JM, Alifano M, Lincet H (2018) How the Warburg effect supports aggressiveness and drug resistance of cancer cells? Drug Resist Updat 38:1–11. https://doi.org/10.1016/j.drup.2018.03.001
Iyengar M, O’Hayer P, Cole A et al (2018) CDK4/6 inhibition as maintenance and combination therapy for high grade serous ovarian cancer. Oncotarget 9(21):15658–15672. https://doi.org/10.18632/oncotarget.24585
James FR, Jiminez-Linan M, Alsop J, Mack M, Song H, Brenton JD, Pharoah PDP, Ali HR (2017) Association between tumour infiltrating lymphocytes, histotype and clinical outcome in epithelial ovarian cancer. BMC Cancer 17(1):657. https://doi.org/10.1186/s12885-017-3585-x
Jia P, Zhao Z (2019) Characterization of tumor-suppressor gene inactivation events in 33 cancer types. Cell Rep 26(2):496–506.e3. https://doi.org/10.1016/j.celrep.2018.12.066
Jiao S, Xia W, Yamaguchi H, Wei Y, Chen MK, Hsu JM, Hsu JL, Yu WH, Du Y, Lee HH, Li CW, Chou CK, Lim SO, Chang SS, Litton J, Arun B, Hortobagyi GN, Hung MC (2017) PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res 23(14):3711–3720. https://doi.org/10.1158/1078-0432.CCR-16-3215
Jiménez-Sánchez A, Cybulska P, Mager KL, Koplev S, Cast O, Couturier DL, Memon D, Selenica P, Nikolovski I, Mazaheri Y, Bykov Y, Geyer FC, Macintyre G, Gavarró LM, Drews RM, Gill MB, Papanastasiou AD, Sosa RE, Soslow RA, Walther T, Shen R, Chi DS, Park KJ, Hollmann T, Reis-Filho JS, Markowetz F, Beltrao P, Vargas HA, Zamarin D, Brenton JD, Snyder A, Weigelt B, Sala E, Miller ML (2020) Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy. Nat Genet 52(6):582–593. https://doi.org/10.1038/s41588-020-0630-5
Jin Y, Wang H, Liang X, Ma J, Wang Y (2014a) Pathological and prognostic significance of hypoxia-inducible factor 1α expression in epithelial ovarian cancer: a meta-analysis. Tumour Biol 35(8):8149–8159. https://doi.org/10.1007/s13277-014-2059-x
Jin Z, Gu J, Xin X, Li Y, Wang H (2014b) Expression of hexokinase 2 in epithelial ovarian tumors and its clinical significance in serous ovarian cancer. Eur J Gynaecol Oncol 35(5):519–524
Kaldawy A, Segev Y, Lavie O et al (2016) Low-grade serous ovarian cancer: a review. Gynecol Oncol 143(2):433–438. https://doi.org/10.1016/j.ygyno.2016.08.320
Kalli KR, Block MS, Kasi PM et al (2018) Folate receptor alpha peptide vaccine generates immunity in breast and ovarian cancer patients. Clin Cancer Res 24(13):3014–3025. https://doi.org/10.1158/1078-0432.CCR-17-2499
Kang HJ, Chun SM, Kim KR, Sohn I, Sung CO (2013) Clinical relevance of gain-of-function mutations of p53 in high-grade serous ovarian carcinoma. PLoS One 8(8):e72609. https://doi.org/10.1371/journal.pone.0072609
Kanska J, Zakhour M, Taylor-Harding B et al (2016) Cyclin E as a potential therapeutic target in high grade serous ovarian cancer. Gynecol Oncol 143(1):152–158. https://doi.org/10.1016/j.ygyno.2016.07.111
Karnezis AN, Cho KR, Gilks CB et al (2017) The disparate origins of ovarian cancers: pathogenesis and prevention strategies. Nat Rev Cancer 17(1):65–74. https://doi.org/10.1038/nrc.2016.113
Karst AM, Jones PM, Vena N, Ligon AH, Liu JF, Hirsch MS, Etemadmoghadam D, Bowtell DD, Drapkin R (2014) Cyclin E1 deregulation occurs early in secretory cell transformation to promote formation of fallopian tube-derived high-grade serous ovarian cancers. Cancer Res 74(4):1141–1152. https://doi.org/10.1158/0008-5472.CAN-13-2247
Kassem L, Abdel-Rahman O (2016) Targeting mTOR pathway in gynecological malignancies: biological rationale and systematic review of published data. Crit Rev Oncol Hematol 108:1–12. https://doi.org/10.1016/j.critrevonc.2016.10.003
Katagiri A, Nakayama K, Rahman MT et al (2010) MEK inhibition suppresses cell invasion and migration in ovarian cancers with activation of ERK1/2. Exp Ther Med 1(4):591–596
Kato N, Sato Y, Kamataki A et al (2018) PIK3CA hotspot mutations and cyclooxygenase-2 expression in ovarian clear cell carcinomas: a close association with stromal features. Hum Pathol. https://doi.org/10.1016/j.humpath.2018.11.013
Kawanishi S, Ohnishi S, Ma N, Hiraku Y, Murata M (2017) Crosstalk between DNA damage and inflammation in the multiple steps of carcinogenesis. Int J Mol Sci 18(8):1808. https://doi.org/10.3390/ijms18081808
Keenan TE, Burke KP, Van Allen EM (2019) Genomic correlates of response to immune checkpoint blockade. Nat Med 25(3):389–402. https://doi.org/10.1038/s41591-019-0382-x
Kelly RJ (2018) Dabrafenib and trametinib for the treatment of non-small cell lung cancer. Expert Rev Anticancer Ther 18(11):1063–1068. https://doi.org/10.1080/14737140.2018.1521272
Khan AQ, Kuttikrishnan S, Siveen KS et al (2018) RAS-mediated oncogenic signaling pathways in human malignancies. Semin Cancer Biol. pii: s1044-579X(18)30002-6. https://doi.org/10.1016/j.semcancer.2018.03.001
Kim K, Park WY, Kim JY et al (2012) Prognostic relevance of the expression of CA IX, GLUT-1, and VEGF in ovarian epithelial cancers. Korean J Pathol 46(6):532–540. https://doi.org/10.4132/KoreanJPathol.2012.46.6.532
Klezovitch O, Vasioukhin V (2015) Cadherin signaling: keeping cells in touch. F1000Res 4(F1000ulty Rev):550. https://doi.org/10.12688/f1000research.6445.1
Klotz DM, Wimberger P (2017) Cells of origin of ovarian cancer: ovarian surface epithelium or fallopian tube? Arch Gynecol Obstet 296(6):1055–1062. https://doi.org/10.1007/s00404-017-4529-z
Klymenko Y, Johnson J, Bos B, Lombard R, Campbell L, Loughran E, Stack MS (2017a) Heterogeneous cadherin expression and multicellular aggregate dynamics in ovarian cancer dissemination. Neoplasia 19(7):549–563. https://doi.org/10.1016/j.neo.2017.04.002
Klymenko Y, Kim O, Loughran E, Yang J, Lombard R, Alber M, Stack MS (2017b) Cadherin composition and multicellular aggregate invasion in organotypic models of epithelial ovarian cancer intraperitoneal metastasis. Oncogene 36(42):5840–5851. https://doi.org/10.1038/onc.2017.171
Knödler M, Körfer J, Kunzmann V et al (2018) Randomised phase II trial to investigate catumaxomab (anti-EpCAM × anti-CD3) for treatment of peritoneal carcinomatosis in patients with gastric cancer. Br J Cancer 119(3):296–302. https://doi.org/10.1038/s41416-018-0150-6
Kobayashi H, Ogawa K, Kawahara N et al (2017) Sequential molecular changes and dynamic oxidative stress in high-grade serous ovarian carcinogenesis. Free Radic Res 51(9–10):755–764. https://doi.org/10.1080/10715762.2017.1383605
Köbel M, Kalloger SE, Boyd N et al (2008) Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med 5(12):e232. https://doi.org/10.1371/journal.pmed.0050232
Köbel M, Reuss A, du Bois A et al (2010) The biological and clinical value of p53 expression in pelvic high-grade serous carcinomas. J Pathol 222(2):191–198. https://doi.org/10.1002/path.2744
Koensgen D, Freitag C, Klaman I et al (2010) Expression and localization of E-cadherin in epithelial ovarian cancer. Anticancer Res 30(7):2525–2530
Konstantinopoulos PA, Barry WT, Birrer M, Westin SN, Cadoo KA, Shapiro GI, Mayer EL, O’Cearbhaill RE, Coleman RL, Kochupurakkal B, Whalen C, Curtis J, Farooq S, Luo W, Eismann J, Buss MK, Aghajanian C, Mills GB, Palakurthi S, Kirschmeier P, Liu J, Cantley LC, Kaufmann SH, Swisher EM, D’Andrea AD, Winer E, Wulf GM, Matulonis UA (2019) Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial. Lancet Oncol 20(4):570–580. https://doi.org/10.1016/S1470-2045(18)30905-7
Kourtidis A, Lu R, Pence LJ, Anastasiadis PZ (2017) A central role for cadherin signaling in cancer. Exp Cell Res 358(1):78–85
Krasner CN, Birrer MJ, Berlin ST, Horowitz NS, Buss MK, Eliasof S et al (2014) Phase II clinical trial evaluating CRLX101 in recurrent ovarian, tubal, and peritoneal cancer. J Clin Oncol 32(Suppl 5):abstr 5581
Krasner CN, Birrer MJ, Berlin ST et al (2015) Targeting VEGFRi resistance through HIF-1á suppression: phase II clinical trial evaluating CRLX101 as monotherapy and in combination with bevacizumab in recurrent platinum resistant ovarian cancer. J Clin Oncol 33(Suppl 15):abstr 5614. https://doi.org/10.1200/jco.2015.33.15_suppl.tps5614
Krasner C, Birrer M, Peters C et al (2016) Abstract CT090: phase II trial of the NDC CRLX101 in combination with bevacizumab in patients with platinum-resistant ovarian cancer (PROC). Cancer Res 76:CT090. https://doi.org/10.1158/1538-7445.AM2016-CT090
Krebs AM, Mitschke J, Lasierra Losada M et al (2017) The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol 19(5):518–529. https://doi.org/10.1038/ncb3513
Krishnamurthy A, Jimeno A (2018) Bispecific antibodies for cancer therapy: a review. Pharmacol Ther 185:122–134. https://doi.org/10.1016/j.pharmthera.2017.12.002
Kristeleit R, Davidenko I, Shirinkin V, El-Khouly F, Bondarenko I, Goodheart MJ, Gorbunova V, Penning CA, Shi JG, Liu X, Newton RC, Zhao Y, Maleski J, Leopold L, Schilder RJ (2017) A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)-only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer. Gynecol Oncol 146(3):484–490. https://doi.org/10.1016/j.ygyno.2017.07.005
Kroeger PT, Drapkin R (2016) Pathogenesis and heterogeneity of ovarian cancer. Curr Opin Obstet Gynecol 29(1):26–34
Kruk J, Aboul-Enein HY (2017) Reactive oxygen and nitrogen species in carcinogenesis: implications of oxidative stress on the progression and development of several cancer types. Mini Rev Med Chem 17(11):904–919. https://doi.org/10.2174/1389557517666170228115324
Książek K (2020) Where does cellular senescence belong in the pathophysiology of ovarian cancer? Semin Cancer Biol. S1044-579X(20)30260-1. https://doi.org/10.1016/j.semcancer.2020.11.021
Kuhn E, Meeker A, Wang TL, Sehdev AS, Kurman RJ, Shih IM (2010) Shortened telomeres in serous tubal intraepithelial carcinoma: an early event in ovarian high-grade serous carcinogenesis. Am J Surg Pathol 34(6):829–836. https://doi.org/10.1097/PAS.0b013e3181dcede7
Kuhn E, Kurman RJ, Vang R, Sehdev AS, Han G, Soslow R, Wang TL, Shih IM (2012) TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma–evidence supporting the clonal relationship of the two lesions. J Pathol 226(3):421–426. https://doi.org/10.1002/path.3023
Kuhn E, Bahadirli-Talbott A, Shih IM (2014) Frequent CCNE1 amplification in endometrial intraepithelial carcinoma and uterine serous carcinoma. Mod Pathol 27(7):1014–1019. https://doi.org/10.1038/modpathol.2013.209
Kuhn E, Wang TL, Doberstein K et al (2016) CCNE1 amplification and centrosome number abnormality in serous tubal intraepithelial carcinoma: further evidence supporting its role as a precursor of ovarian high-grade serous carcinoma. Mod Pathol 29(10):1254–1261. https://doi.org/10.1038/modpathol.2016.101
Kurtz J, Marth C, Oaknin A, Asselain B, Baumann K, Cibula D et al (2018) ATALANTE (ENGOT-ov29): a randomized, double-blinded, phase III study of atezolizumab versus placebo in patients with late relapse of epithelial ovarian, fallopian tube, or peritoneal cancer treated by platinum-based chemotherapy and bevacizumab. J Clin Oncol 36(Suppl):abstr TPS5607
Kuznetsova AY, Seget K, Moeller GK et al (2015) Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells. Cell Cycle 14(17):2810–2820
Kyriakopoulos CE, Braden AM, Kolesar JM et al (2016) A phase I study of tivantinib in combination with temsirolimus in patients with advanced solid tumors. Invest New Drugs 35(3):290–297
Labidi-Galy SI, Papp E, Hallberg D et al (2017) High grade serous ovarian carcinomas originate in the fallopian tube. Nat Commun 8(1):1093. https://doi.org/10.1038/s41467-017-00962-1
Lam T, Aguirre-Ghiso JA, Geller MA, Aksan A, Azarin SM (2020) Immobilization rapidly selects for chemoresistant ovarian cancer cells with enhanced ability to enter dormancy. Biotechnol Bioeng 117(10):3066–3080. https://doi.org/10.1002/bit.27479
Lambert AW, Pattabiraman DR, Weinberg RA (2017) Emerging biological principles of metastasis. Cell 168(4):670–691. https://doi.org/10.1016/j.cell.2016.11.037
Lampert EJ, Zimmer A, Padget M, Cimino-Mathews A, Nair JR, Liu Y, Swisher EM, Hodge JW, Nixon AB, Nichols E, Bagheri MH, Levy E, Radke MR, Lipkowitz S, Annunziata CM, Taube JM, Steinberg SM, Lee JM (2020) Combination of PARP inhibitor olaparib, and PD-L1 inhibitor durvalumab, in recurrent ovarian cancer: a proof-of-concept phase II study. Clin Cancer Res 26(16):4268–4279. https://doi.org/10.1158/1078-0432.CCR-20-0056
Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149(2):274–293. https://doi.org/10.1016/j.cell.2012.03.017
Lau MT, So WK, Leung PC (2013) Fibroblast growth factor 2 induces E-cadherin down-regulation via PI3K/Akt/mTOR and MAPK/ERK signaling in ovarian cancer cells. PLoS One 8(3):e59083
Le Page C, Amuzu S, Rahimi K, Gotlieb W, Ragoussis J, Tonin PN (2020) Lessons learned from understanding chemotherapy resistance in epithelial tubo-ovarian carcinoma from BRCA1and BRCA2mutation carriers. Semin Cancer Biol. S1044-579X(20)30177-2. https://doi.org/10.1016/j.semcancer.2020.08.005
Le Saux O, Ray-Coquard I, Labidi-Galy SI (2020) Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer. Semin Cancer Biol. S1044-579X(20)30193-0. https://doi.org/10.1016/j.semcancer.2020.08.017
Leckband DE, de Rooij J (2014) Cadherin adhesion and mechanotransduction. Annu Rev Cell Dev Biol 30:291–315. https://doi.org/10.1146/annurev-cellbio-100913-013212
Ledermann JA, Canevari S, Thigpen T (2015) Targeting the folate receptor: diagnostic and therapeutic approaches to personalize cancer treatments. Ann Oncol 26(10):2034–2043. https://doi.org/10.1093/annonc/mdv250
Ledermann JA, Embleton AC, Raja F, Perren TJ, Jayson GC, GJS R, Kaye SB, Hirte H, Eisenhauer E, Vaughan M, Friedlander M, González-Martín A, Stark D, Clark E, Farrelly L, Swart AM, Cook A, Kaplan RS, MKB P, ICON6 collaborators (2016) Cediranib in patients with relapsed platinum sensitive ovarian cancer (ICON6): a randomised, double-blind, placebocontrolled phase 3 trial. Lancet 387(10023):1066–1074. https://doi.org/10.1016/S0140-6736(15)01167-8. Erratum in: Lancet. 2016 Apr23;387(10029):1722
Ledermann JA, Colombo N, Oza M et al (2020) Avelumab in combination with and/or following chemotherapy vs chemotherapy alone in patients with previously untreated epithelial ovarian cancer: results from the phase 3 javelin ovarian 100 trial. Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. LBA 25, Scientific Plenary. https://doi.org/10.1016/j.ygyno.2020.06.025
Lee EK, Matulonis UA (2020) Emerging drugs for the treatment of ovarian cancer: a focused review of PARP inhibitors. Expert Opin Emerg Drugs 25(2):165–188. https://doi.org/10.1080/14728214.2020.1773791
Lee WH, Bookstein R, Hong F et al (1987) Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 235(4794):1394–1399
Lee JG, Ahn JH, Jin Kim T, Ho Lee J, Choi JH (2015) Mutant p53 promotes ovarian cancer cell adhesion to mesothelial cells via integrin β4 and Akt signals. Sci Rep 5:12642. https://doi.org/10.1038/srep12642
Lee EK, Xiong N, Cheng SC, Barry WT, Penson RT, Konstantinopoulos PA, Hoffman MA, Horowitz N, Dizon DS, Stover EH, Wright AA, Campos SM, Krasner C, Morrissey S, Whalen C, Quinn R, Matulonis UA, Liu JF (2020) Combined pembrolizumab and pegylated liposomal doxorubicin in platinum resistant ovarian cancer: a phase 2 clinical trial. Gynecol Oncol 159(1):72–78. https://doi.org/10.1016/j.ygyno.2020.07.028
Legge F, Paglia A, D’Asta M et al (2011) Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients. BMC Cancer 11:214. https://doi.org/10.1186/1471-2407-11-214
Leijen S, van Geel RM, Sonke GS, de Jong D, Rosenberg EH, Marchetti S, Pluim D, van Werkhoven E, Rose S, Lee MA, Freshwater T, Beijnen JH, Schellens JH (2016) Phase II study of WEE1 inhibitor AZD1775s carboplatin in patients with TP53-mutated ovarian cancer refractory or resistant to first-line therapy within 3 months. J Clin Oncol 34(36):4354–4361. https://doi.org/10.1200/JCO.2016.67.5942
Leroy B, Anderson M, Soussi T (2014) TP53 mutations in human cancer: database reassessment and prospects for the next decade. Hum Mutat 35(6):672–688. https://doi.org/10.1002/humu.22552
Lheureux S, N’Diaye M, Blanc-Fournier C, Dugué AE, Clarisse B, Dutoit S, Giffard F, Abeilard E, Briand M, Labiche A, Grellard JM, Crouet H, Martin S, Joly F, Poulain L (2015) Identification of predictive factors of response to the BH3-mimetic molecule ABT-737: an ex vivo experiment in human serous ovarian carcinoma. Int J Cancer 136(5):E340–E350. https://doi.org/10.1002/ijc.29104
Lheureux S, Cristea MC, Bruce JP, Garg S, Cabanero M, Mantia-Smaldone G, Olawaiye AB, Ellard SL, Weberpals JI, Wahner Hendrickson AE, Fleming GF, Welch S, Dhani NC, Stockley T, Rath P, Karakasis K, Jones GN, Jenkins S, Rodriguez-Canales J, Tracy M, Tan Q, Bowering V, Udagani S, Wang L, Kunos CA, Chen E, Pugh TJ, Oza AM (2021) Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet 397(10271):281–292. https://doi.org/10.1016/S0140-6736(20)32554-X
Li H, Zhang R (2013) Role of EZH2 in epithelial ovarian cancer: from biological insights to therapeutic target. Front Oncol 3:47. https://doi.org/10.3389/fonc.2013.00047
Li SB, Schwartz PE, Lee WH et al (1991) Allele loss at the retinoblastoma locus in human ovarian cancer. J Natl Cancer Inst 83(9):637–640
Li W, Xu XL, Zhang J, Cai JH, Tang YX (2012) Effects of cyclooxygenase inhibitors on survival time in ovarian cancer xenograft-bearing mice. Oncol Lett 4(6):1269–1273. https://doi.org/10.3892/ol.2012.929
Li H, Zeng J, Shen K (2014) PI3K/AKT/mTOR signaling pathway as a therapeutic target for ovarian cancer. Arch Gynecol Obstet 290(6):1067–1078. https://doi.org/10.1007/s00404-014-3377-3
Li C, Bonazzoli E, Bellone S et al (2019a) Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors. Proc Natl Acad Sci U S A 116(2):619–624. https://doi.org/10.1073/pnas.1814027116
Li VD, Li KH, Li JT (2019b) TP53 mutations as potential prognostic markers for specific cancers: analysis of data from The Cancer Genome Atlas and the International Agency for Research on Cancer TP53 Database. J Cancer Res Clin Oncol 145(3):625–636. https://doi.org/10.1007/s00432-018-2817-z
Li N, Li H, Wang Y, Cao L, Zhan X (2020) Quantitative proteomics revealed energy metabolism pathway alterations in human epithelial ovarian carcinoma and their regulation by the antiparasite drug ivermectin: data interpretation in the context of 3P medicine. EPMA J 11(4):661–694. https://doi.org/10.1007/s13167-020-00224-z
Li J, Zou Y, Pei M, Zhang Y, Jiang Y (2021) Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells. J Cancer 12(1):207–216. https://doi.org/10.7150/jca.48896
Lin Q, Liu W, Xu S, Shang H, Li J, Guo Y, Tong J (2021) PARP inhibitors as maintenance therapy in newly diagnosed advanced ovarian cancer: a meta-analysis. BJOG 128(3):485–493. https://doi.org/10.1111/1471-0528.16411
Lincet H, Kafara P, Giffard F, Abeilard-Lemoisson E, Duval M, Louis MH, Poulain L, Icard P (2013) Inhibition of Mcl-1 expression by citrate enhances the effect of Bcl-xL inhibitors on human ovarian carcinoma cells. J Ovarian Res 6(1):72. https://doi.org/10.1186/1757-2215-6-72
Liu F, Yang X, Geng M, Huang M (2018) Targeting ERK, an Achilles’ Heel of the MAPK pathway, in cancer therapy. Acta Pharm Sin B 8(4):552–562
Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel BJ, Buss MK, Nattam SR, Hurteau J, Luo W, Curtis J, Whalen C, Kohn EC, Ivy SP, Matulonis UA (2019a) Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. Ann Oncol 30(4):551–557. https://doi.org/10.1093/annonc/mdz018
Liu JF, Gordon M, Veneris J, Braiteh F, Balmanoukian A, Eder JP, Oaknin A, Hamilton E, Wang Y, Sarkar I, Molinero L, Fassò M, O’Hear C, Lin YG, Emens LA (2019b) Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancers. Gynecol Oncol 154(2):314–322. https://doi.org/10.1016/j.ygyno.2019.05.021
Liu JF, Herold C, Gray KP et al (2019c) Assessment of combined nivolumab and bevacizumab in relapsed ovarian cancer: a phase 2 clinical trial [published online ahead of print, 2019]. JAMA Oncol 5(12):1731–1738. https://doi.org/10.1001/jamaoncol.2019.3343
Loeian MS, Mehdi Aghaei S, Farhadi F et al (2019) Liquid biopsy using the nanotube-CTC-chip: capture of invasive CTCs with high purity using preferential adherence in breast cancer patients. Lab Chip 19(11):1899–1915. https://doi.org/10.1039/c9lc00274j
Long GV, Hauschild A, Santinami M et al (2017a) Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med 377(19):1813–1823. https://doi.org/10.1056/NEJMoa1708539
Long GV, Flaherty KT, Stroyakovskiy D et al (2017b) Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Ann Oncol 28(7):1631–1639
Lord CJ, Ashworth A (2012) The DNA damage response and cancer therapy. Nature 481:287. https://doi.org/10.1038/nature10760
LoRusso PM (2016) Inhibition of the PI3K/AKT/mTOR pathway in solid tumors. J Clin Oncol 34(31):3803–3815. https://doi.org/10.1200/JCO.2014.59.0018
Lu J, Chen H, He F, You Y, Feng Z, Chen W, Li X, Zhao L (2020) Ginsenoside 20(S)-Rg3 upregulates HIF-1α-targeting miR-519a-5p to inhibit the Warburg effect in ovarian cancer cells. Clin Exp Pharmacol Physiol 47(8):1455–1463. https://doi.org/10.1111/1440-1681.13321
Lundgren C, Ahlin C, Holmberg L et al (2015) Cyclin E1 is a strong prognostic marker for death from lymph node negative breast cancer. A population-based case-control study. Acta Oncol 54(4):538–544. https://doi.org/10.3109/0284186X.2014.965274
Luo H, Xu X, Ye M, Sheng B, Zhu X (2018) The prognostic value of HER2 in ovarian cancer: a meta-analysis of observational studies. PLoS One 13(1):e0191972. https://doi.org/10.1371/journal.pone.0191972
Luther C, Swami U, Zhang J et al (2019) Advanced stage melanoma therapies: detailing the present and exploring the future. Crit Rev Oncol Hematol 133:99–111. https://doi.org/10.1016/j.critrevonc.2018.11.002
Ma Y, Wang W, Idowu MO et al (2018a) Ovarian cancer relies on glucose transporter 1 to fuel glycolysis and growth: anti-tumor activity of BAY-876. Cancers (Basel) 11(1):33. https://doi.org/10.3390/cancers11010033
Ma C, Zhao JZ, Lin RT et al (2018b) Combined overexpression of cadherin 6, cadherin 11 and cluster of differentiation 44 is associated with lymph node metastasis and poor prognosis in oral squamous cell carcinoma. Oncol Lett 15(6):9498–9506
Mabuchi S, Kuroda H, Takahashi R et al (2015) The PI3K/AKT/mTOR pathway as a therapeutic target in ovarian cancer. Gynecol Oncol 137(1):173–179. https://doi.org/10.1016/j.ygyno.2015.02.003
Macpherson AM, Barry SC, Ricciardelli C, Oehler MK (2020) Epithelial ovarian cancer and the immune system: biology, interactions, challenges and potential advances for immunotherapy. J Clin Med 9(9):2967. https://doi.org/10.3390/jcm9092967
Mandilaras V, Garg S, Cabanero M, Tan Q, Pastrello C, Burnier J, Karakasis K, Wang L, Dhani NC, Butler MO, Bedard PL, Siu LL, Clarke B, Shaw PA, Stockley T, Jurisica I, Oza AM, Lheureux S (2019) TP53 mutations in high grade serous ovarian cancer and impact on clinical outcomes: a comparison of next generation sequencing and bioinformatics analyses. Int J Gynecol Cancer. https://doi.org/10.1136/ijgc-2018-000087
Manning AL, Dyson NJ (2012) RB: mitotic implications of a tumour suppressor. Nat Rev Cancer 12(3):220–226. https://doi.org/10.1038/nrc3216
Marth C, Vergote I, Scambia G, Oberaigner W, Clamp A, Berger R, Kurzeder C, Colombo N, Vuylsteke P, Lorusso D, Hall M, Renard V, Pignata S, Kristeleit R, Altintas S, Rustin G, Wenham RM, Mirza MR, Fong PC, Oza A, Monk BJ, Ma H, Vogl FD, Bach BA (2017) ENGOT-ov-6/TRINOVA-2: randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer. Eur J Cancer 70:111–121. https://doi.org/10.1016/j.ejca.2016.09.004
Martin de la Fuente L, Westbom-Fremer S, Arildsen NS, Hartman L, Malander S, Kannisto P, Måsbäck A, Hedenfalk I (2020) PD-1/PD-L1 expression and tumor-infiltrating lymphocytes are prognostically favorable in advanced high-grade serous ovarian carcinoma. Virchows Arch 477(1):83–91. https://doi.org/10.1007/s00428-020-02751-6
Martin LP, Konner JA, Moore KN et al (2017) Characterization of folate receptor alpha (FRα) expression in archival tumor and biopsy samples from relapsed epithelial ovarian cancer patients: a phase I expansion study of the FRα-targeting antibody-drug conjugate mirvetuximab soravtansine. Gynecol Oncol 147(2):402–407. https://doi.org/10.1016/j.ygyno.2017.08.015
Martins FC, Santiago ID, Trinh A et al (2014) Combined image and genomic analysis of high-grade serous ovarian cancer reveals PTEN loss as a common driver event and prognostic classifier. Genome Biol 15(12):526. https://doi.org/10.1186/s13059-014-0526-8
Martowicz A, Spizzo G, Gastl G, Untergasser G (2012) Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines. BMC Cancer 12:501. https://doi.org/10.1186/1471-2407-12-501
Mattmann ME, Stoops SL, Lindsley CW (2011) Inhibition of Akt with small molecules and biologics: historical perspective and current status of the patent landscape. Expert Opin Ther Pat 21(9):1309–1338
Matulonis UA, Wulf GM, Barry WT et al (2016) Phase I dose escalation study of the PI3kinase pathway inhibitor BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib for the treatment of high-grade serous ovarian and breast cancer. Ann Oncol 28(3):512–518
Matulonis UA, Moore KN, Martin LP et al (2018) Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), with pembrolizumab in platinum-resistant ovarian cancer (PROC): initial results of an expansion cohort from FORWARD II, a phase Ib study. Ann Oncol 29. https://doi.org/10.1093/annonc/mdy285.157
Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, Raspagliesi F, Sonke GS, Birrer M, Provencher DM, Sehouli J, Colombo N, González-Martín A, Oaknin A, Ottevanger PB, Rudaitis V, Katchar K, Wu H, Keefe S, Ruman J, Ledermann JA (2019) Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol 30(7):1080–1087. https://doi.org/10.1093/annonc/mdz135
McAlpine JN, Porter H, Köbel M et al (2012) BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma. Mod Pathol 25(5):740–750. https://doi.org/10.1038/modpathol.2011.211
McCormick A, Earp E, Leeson C et al (2016) Phosphatase and tensin homolog is a potential target for ovarian cancer sensitization to cytotoxic agents. Int J Gynecol Cancer 26(4):632–639. https://doi.org/10.1097/IGC.0000000000000657
McLachlan J, Gore M, Banerjee S (2016a) Targeting the mitogen-activated protein kinase pathway in low-grade serous carcinoma of the ovary. Pharmacogenomics 17(12):1353–1363. https://doi.org/10.2217/pgs.16.24
McLachlan J, Lima JP, Dumas L, Banerjee S (2016b) Targeted agents and combinations in ovarian cancer: where are we now? Expert Rev Anticancer Ther 16(4):441–454. https://doi.org/10.1586/14737140.2016.1162101
McMullen M, Madariaga A, Lheureux S (2020) New approaches for targeting platinum-resistant ovarian cancer. Semin Cancer Biol. S1044-579X(20)30186-3. https://doi.org/10.1016/j.semcancer.2020.08.013
Mendivil AA, Tung PK, Bohart R, Bechtol K, Goldstein BH (2018) Dramatic clinical response following dabrafenib and trametinib therapy in a heavily pretreated low grade serous ovarian carcinoma patient with a BRAF V600E mutation. Gynecol Oncol Rep 26:41–44. https://doi.org/10.1016/j.gore.2018.09.002
Meng E, Taylor B, Ray A, Shevde LA, Rocconi RP (2012) Targeted inhibition of telomerase activity combined with chemotherapy demonstrates synergy in eliminating ovarian cancer spheroid-forming cells. Gynecol Oncol 124(3):598–605. https://doi.org/10.1016/j.ygyno.2011.11.018
Mesnage SJL, Auguste A, Genestie C, Dunant A, Pain E, Drusch F, Gouy S, Morice P, Bentivegna E, Lhomme C, Pautier P, Michels J, Le Formal A, Cheaib B, Adam J, Leary AF (2017) Neoadjuvant chemotherapy (NACT) increases immune infiltration and programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC). Ann Oncol 28(3):651–657. https://doi.org/10.1093/annonc/mdw625
Milea A, George SH, Matevski D et al (2014) Retinoblastoma pathway deregulatory mechanisms determine clinical outcome in high-grade serous ovarian carcinoma. Mod Pathol 27(7):991–1001. https://doi.org/10.1038/modpathol.2013.218
Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA, ENGOT-OV16/NOVA Investigators (2016) Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 375(22):2154–2164. https://doi.org/10.1056/NEJMoa1611310
Mirza MR, Pignata S, Ledermann JA (2018) Latest clinical evidence and further development of PARP inhibitors in ovarian cancer. Ann Oncol 29(6):1366–1376. https://doi.org/10.1093/annonc/mdy174
Mirza MR, Coleman RL, González-Martín A, Moore KN, Colombo N, Ray-Coquard I, Pignata S (2020) The forefront of ovarian cancer therapy: update on PARP inhibitors. Ann Oncol 31(9):1148–1159. https://doi.org/10.1016/j.annonc.2020.06.004
Miše BP, Telesmanić VD, Tomić S et al (2015) Correlation between E-cadherin immunoexpression and efficacy of first line platinum-based chemotherapy in advanced high grade serous ovarian cancer. Pathol Oncol Res 21(2):347–356. https://doi.org/10.1007/s12253-014-9827-1
Mitsudomi T, Yatabe Y (2010) Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J 277(2):301–308. https://doi.org/10.1111/j.1742-4658.2009.07448.x
Mittal K, Donthamsetty S, Kaur R et al (2017) Multinucleated polyploidy drives resistance to Docetaxel chemotherapy in prostate cancer. Br J Cancer 116(9):1186–1194
Moiseeva O, Guillon J, Ferbeyre G (2020) Senescence: a program in the road to cell elimination and cancer. Semin Cancer Biol. S1044-579X(20)30277-7. https://doi.org/10.1016/j.semcancer.2020.12.017
Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhommé C, Richardson G, Rincón DG, Coleman RL, Herzog TJ, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Tassoudji M, Navale L, Warner DJ, Oza AM (2014) Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 15(8):799–808. https://doi.org/10.1016/S1470-2045(14)70244-X
Monk BJ, Brady MF, Aghajanian C, Lankes HA, Rizack T, Leach J, Fowler JM, Higgins R, Hanjani P, Morgan M, Edwards R, Bradley W, Kolevska T, Foukas P, Swisher EM, Anderson KS, Gottardo R, Bryan JK, Newkirk M, Manjarrez KL, Mannel RS, Hershberg RM, Coukos G (2017) A phase 2, randomized, double-blind, placebo-controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study. Ann Oncol 28(5):996–1004. https://doi.org/10.1093/annonc/mdx049
Moore KN, Pignata S (2019) Trials in progress: imagyn050/GOG 3015/ENGOT-OV39. A Phase III, multicenter, randomized study of atezolizumab versus placebo administered in combination with paclitaxel, carboplatin, and bevacizumab to patients with newly-diagnosed stage III or stage IV ovarian, fallopian tube, or primary peritoneal cancer. Int J Gynecol Cancer. https://doi.org/10.1136/ijgc-2018-000071
Moore KN, Borghaei H, O’Malley DM et al (2017) Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors. Cancer 123(16):3080–3087. https://doi.org/10.1002/cncr.30736
Moore KN, Martin LP, O’Malley DM et al (2018a) A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer. Future Oncol 14(2):123–136. https://doi.org/10.2217/fon-2017-0379
Moore KN, O’Malley DM, Vergote I et al (2018b) Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer. Gynecol Oncol 151(1):46–52. https://doi.org/10.1016/j.ygyno.2018.07.017
Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P (2018c) Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 379(26):2495–2505. https://doi.org/10.1056/NEJMoa1810858
Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, Wahner Hendrickson AE, Azodi M, DiSilvestro P, Oza AM, Cristea M, Berek JS, Chan JK, Rimel BJ, Matei DE, Li Y, Sun K, Luptakova K, Matulonis UA, Monk BJ (2019a) Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 20(5):636–648. https://doi.org/10.1016/S1470-2045(19)30029-4
Moore KN, Oza AM, Colombo N et al (2019b) FORWARD I (GOG 3011): a Phase III study of mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), versus chemotherapy in patients (pts) with platinum-resistant ovarian cancer (PROC). Ann Oncol 30(Suppl 5):v403–v434. https://doi.org/10.1093/annonc/mdz250
Moore KN, Bookman M, Sehouli J (2020) LBA31 primary results from IMagyn050/GOG 3015/ENGOT-OV39, a double-blind placebo (pbo)-controlled randomised phase III trial of bevacizumab (bev)-containing therapy ± atezolizumab (atezo) for newly diagnosed stage III/IV ovarian cancer (OC). Ann Oncol. https://doi.org/10.1016/j.annonc.2020.08.2261
Moroney JW, Powderly J, Lieu CH, Bendell JC, Eckhardt SG, Chang CW, Molinero L, Spahn J, Williams P, Lin YG, Hodi FS (2020) Safety and clinical activity of atezolizumab plus bevacizumab in patients with ovarian cancer: a phase Ib study. Clin Cancer Res 26(21):5631–5637. https://doi.org/10.1158/1078-0432.CCR-20-0477
Morrison J, Thoma C, Goodall RJ et al (2018) Epidermal growth factor receptor blockers for the treatment of ovarian cancer. Cochrane Database Syst Rev 10:CD007927. https://doi.org/10.1002/14651858.CD007927
Morse CB, Toukatly MN, Kilgore MR, Agnew KJ, Bernards SS, Norquist BM, Pennington KP, Garcia RL, Liao JB, Swisher EM (2019) Tumor infiltrating lymphocytes and homologous recombination deficiency are independently associated with improved survival in ovarian carcinoma. Gynecol Oncol 153(2):217–222. https://doi.org/10.1016/j.ygyno.2019.02.011
Moujaber T, Etemadmoghadam D, Kennedy CJ et al (2018) BRAF mutations in low-grade serous ovarian cancer and response to BRAF inhibition. JCO Precis Oncol 2:1–14. https://doi.org/10.1200/PO.17.00221
Mrozik KM, Blaschuk OW, Cheong CM et al (2018) N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer 18:939. https://doi.org/10.1186/s12885-018-4845-0
Murakami R, Matsumura N, Brown JB et al (2017) Exome sequencing landscape analysis in ovarian clear cell carcinoma shed light on key chromosomal regions and mutation gene networks. Am J Pathol 187(10):2246–2258. https://doi.org/10.1016/j.ajpath.2017.06.012
Murakami R, Matsumura N, Michimae H et al (2019) The mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin than to conventional taxane and carboplatin chemotherapy in high grade serous ovarian carcinoma: a survey of Japanese Gynecologic Oncology Group study (JGOG3016A1). Gynecol Oncol 153(2):312–319. https://doi.org/10.1016/j.ygyno.2019.02.010
Nadkarni NJ, Geest KD, Neff T et al (2013) Microvessel density and p53 mutations in advanced-stage epithelial ovarian cancer. Cancer Lett 331(1):99–104. https://doi.org/10.1016/j.canlet.2012.12.016
Nakayama N, Nakayama K, Shamima Y et al (2010) Gene amplification CCNE1 is related to poor survival and potential therapeutic target in ovarian cancer. Cancer 116(11):2621–2634. https://doi.org/10.1002/cncr.24987
Naumann RW, Coleman RL, Burger RA et al (2013) PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer. J Clin Oncol 31(35):4400–4406. https://doi.org/10.1200/JCO.2013.49.7685
O’Malley DM, Matulonis UA, Birrer MJ, Castro CM, Gilbert L, Vergote I, Martin LP, Mantia-Smaldone GM, Martin AG, Bratos R, Penson RT, Malek K, Moore KN (2020) Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecol Oncol 157(2):379–385. https://doi.org/10.1016/j.ygyno.2020.01.037
Oh J, Barve M, Matthews CM, Koon EC, Heffernan TP, Fine B, Grosen E, Bergman MK, Fleming EL, DeMars LR, West L, Spitz DL, Goodman H, Hancock KC, Wallraven G, Kumar P, Bognar E, Manning L, Pappen BO, Adams N, Senzer N, Nemunaitis J (2016) Phase II study of Vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer. Gynecol Oncol 143(3):504–510. https://doi.org/10.1016/j.ygyno.2016.09.018
Orbegoso C, Marquina G, George A, Banerjee S (2017) The role of Cediranib in ovarian cancer. Expert Opin Pharmacother 18(15):1637–1648. https://doi.org/10.1080/14656566.2017.1383384
Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Park-Simon TW, Rustin G, Joly F, Mirza MR, Plante M, Quinn M, Poveda A, Jayson GC, Stark D, Swart AM, Farrelly L, Kaplan R, Parmar MK, Perren TJ, ICON7 Trial Investigators (2015a) Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol 16(8):928–936. https://doi.org/10.1016/S1470-2045(15)00086-8
Oza AM, Vergote IB, Gilbert LG, Lucy P, Ghatage A, Lisyankaya S et al (2015b) A randomized double-blind phase III trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD/Doxil®/Caelyx®) in combination versus PLD in participants with platinum-resistant ovarian cancer (PROCEED) (NCT01170650). Gynecol Oncol 137:5–6. https://doi.org/10.1016/j.ygyno.2015.01.010
Oza AM, Estevez-Diz M, Grischke EM, Hall M, Marmé F, Provencher D, Uyar D, Weberpals JI, Wenham RM, Laing N, Tracy M, Freshwater T, Lee MA, Liu J, Qiu J, Rose S, Rubin EH, Moore K (2020) A biomarker-enriched, randomized phase II trial of adavosertib (AZD1775) plus paclitaxel and carboplatin for women with platinum-sensitive TP53-mutant ovarian cancer. Clin Cancer Res 26(18):4767–4776. https://doi.org/10.1158/1078-0432.CCR-20-0219
Pal M, Bhattacharya S, Kalyan G et al (2018) Cadherin profiling for therapeutic interventions in Epithelial Mesenchymal Transition (EMT) and tumorigenesis. Exp Cell Res 368(2):137–146. https://doi.org/10.1016/j.yexcr.2018.04.014
Palaia I, Tomao F, Sassu CM, Musacchio L, Benedetti Panici P (2020) Immunotherapy for ovarian cancer: recent advances and combination therapeutic approaches. Onco Targets Ther 13:6109–6129. https://doi.org/10.2147/OTT.S205950
Papa S, Choy PM, Bubici C (2018) The ERK and JNK pathways in the regulation of metabolic reprogramming. Oncogene. https://doi.org/10.1038/s41388-018-0582-8
Pascale RM, Calvisi DF, Simile MM, Feo CF, Feo F (2020) The Warburg effect 97 years after its discovery. Cancers (Basel) 12(10):2819. https://doi.org/10.3390/cancers12102819
Pasquali S, Hadjinicolaou AV, Chiarion Sileni V, Rossi CR, Mocellin S (2018) Systemic treatments for metastatic cutaneous melanoma. Cochrane Database Syst Rev 2(2):CD011123. https://doi.org/10.1002/14651858.CD011123.pub2
Patch AM, Christie EL, Etemadmoghadam D et al (2015) Whole-genome characterization of chemoresistant ovarian cancer. Nature 521(7553):489–494. https://doi.org/10.1038/nature14410
Patel IS, Madan P, Getsios S et al (2003) Cadherin switching in ovarian cancer progression. Int J Cancer 106(2):172–177
Pathak SJ, Mueller JL, Okamoto K et al (2019) EPCAM mutation update: variants associated with congenital tufting enteropathy and Lynch syndrome. Hum Mutat 40(2):142–161. https://doi.org/10.1002/humu.23688
Patriarca C, Macchi RM, Marschner AK, Mellstedt H (2012) Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat Rev 38(1):68–75. https://doi.org/10.1016/j.ctrv.2011.04.002
Pearce CL, Templeman C, Rossing MA et al (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 13(4):385–394
Peng HL, He L, Zhao X (2012) Association of reduced immunohistochemical expression of E-cadherin with a poor ovarian cancer prognosis--results of a meta-analysis. Asian Pac J Cancer Prev 13(5):2003–2007
Peng DH, Kundu ST, Fradette JJ et al (2019) ZEB1 suppression sensitizes KRAS mutant cancers to MEK inhibition by an IL17RD-dependent mechanism. Sci Transl Med 11(483):eaaq1238. https://doi.org/10.1126/scitranslmed.aaq1238
Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA III, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G (2020) Olaparib versus nonplatinum chemotherapy in patients with platinum-sensitive relapsed ovarian cancer and a germline BRCA1/2 mutation (SOLO3): a randomized phase III trial. J Clin Oncol 38(11):1164–1174. https://doi.org/10.1200/JCO.19.02745
Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM, ICON7 Investigators (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365(26):2484–2496. https://doi.org/10.1056/NEJMoa1103799. Erratum in: N Engl J Med 2012;366(3):284
Petersen S, Wilson AJ, Hirst J, Roby KF, Fadare O, Crispens MA, Beeghly-Fadiel A, Khabele D (2020) CCNE1 and BRD4 co-amplification in high-grade serous ovarian cancer is associated with poor clinical outcomes. Gynecol Oncol 157(2):405–410. https://doi.org/10.1016/j.ygyno.2020.01.038
Pétigny-Lechartier C, Duboc C, Jebahi A et al (2017) The mTORC1/2 inhibitor AZD8055engthens the efficiency of the MEK inhibitor trametinib to reduce the Mcl-1/[Bim and Puma] ratio and to sensitize ovarian carcinoma cells to ABT-737. Mol Cancer Ther 16(1):102–115. https://doi.org/10.1158/1535-7163.MCT-16-0342
Petrillo M et al (2016) Targeting the hallmarks of ovarian cancer: the big picture. Gynecol Oncol 142:176–183
Pham E, Birrer MJ, Eliasof S, Garmey EG, Lazarus D, Lee CR, Man S, Matulonis UA, Peters CG, Xu P, Krasner C, Kerbel RS (2015) Translational impact of nanoparticle-drug conjugate CRLX101 with or without bevacizumab in advanced ovarian cancer. Clin Cancer Res 21(4):808–818. https://doi.org/10.1158/1078-0432.CCR-14-28102868
Piha-Paul SA, Wheler JJ, Fu S et al (2014) Advanced gynecologic malignancies treated with a combination of the VEGF inhibitor bevacizumab and the mTOR inhibitor temsirolimus. Oncotarget 5(7):1846–1855
Pils D, Bachmayr-Heyda A, Auer K et al (2014) Cyclin E1 (CCNE1) as independent positive prognostic factor in advanced stage serous ovarian cancer patients – a study of the OVCAD consortium. Eur J Cancer 50(1):99–110. https://doi.org/10.1016/j.ejca.2013.09.011
Poveda A, Floquet A, Ledermann JA et al (2020) Final overall survival results from SOLO2/ENGOT-ov21: a phase III trial assessing maintenance olaparib in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation. ASCO20 Virtual Scientific Program. Abstract 6002. Presented at press briefing on May 12, 2020
Pradeep S, Kim SW, Wu SY et al (2014) Hematogenous metastasis of ovarian cancer: rethinking mode of spread. Cancer Cell 26(1):77–91. https://doi.org/10.1016/j.ccr.2014.05.002
Prat J, D’Angelo E, Espinosa I (2018) Ovarian carcinomas: at least five different diseases with distinct histological features and molecular genetics. Hum Pathol 80:11–27. https://doi.org/10.1016/j.humpath.2018.06.018
Prislei S, Martinelli E, Zannoni GF et al (2015) Role and prognostic significance of the epithelial-mesenchymal transition factor ZEB2 in ovarian cancer. Oncotarget 6(22):18966–18979. https://doi.org/10.18632/oncotarget.3943
Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I (2014) Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol 32(13):1302–1308. https://doi.org/10.1200/JCO.2013.51.4489
Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P, SOLO2/ENGOT-Ov21 Investigators (2017) Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 18(9):1274–1284. https://doi.org/10.1016/S1470-2045(17)30469-2. Epub 2017. Erratum in: Lancet Oncol 2017;18(9):e510
Pujade-Lauraine E, Fujiwara K, Dychter SS, Devgan G, Monk BJ (2018) Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: javelin Ovarian 200 Phase III study design. Future Oncol 14(21):2103–2113. https://doi.org/10.2217/fon-2018-0070
Pujade-Lauraine E, Fujiwara K, Ledermann JAL et al (2019) Avelumab alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in platinum-resistant or refractory epithelial ovarian cancer: primary and biomarker analysis of the phase III JAVELIN Ovarian 200 trial. Soc Gynecol Oncol Annual Meeting. (LBA1). https://www.sgo50.org/wp-content/uploads/2019/03/SGO-2019-Late-Breaking-Abstracts.pdf. Accessed 16 Jan 2021
Qiao Y, Yang T, Gan Y et al (2018) Associations between aspirin use and the risk of cancers: a meta-analysis of observational studies. BMC Cancer 18(1):288. https://doi.org/10.1186/s12885-018-4156-5
Qiu C, Lu N, Wang X et al (2017) Gene expression profiles of ovarian low-grade serous carcinoma resemble those of fallopian tube epithelium. Gynecol Oncol 147(3):634–641. https://doi.org/10.1016/j.ygyno.2017.09.029
Rafehi S, Ramos Valdes Y, Bertrand M et al (2016) TGFβ signaling regulates epithelial-mesenchymal plasticity in ovarian cancer ascites-derived spheroids. Endocr Relat Cancer 23(3):147–159. https://doi.org/10.1530/ERC-15-0383
Rahman M, Nakayama K, Rahman MT et al (2012) Clinicopathologic and biological analysis of PIK3CA mutation in ovarian clear cell carcinoma. Hum Pathol 43(12):2197–2206. https://doi.org/10.1016/j.humpath.2012.03.011
Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P, PAOLA-1 Investigators (2019) Olaparib plus Bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med 381(25):2416–2428. https://doi.org/10.1056/NEJMoa1911361
Rechsteiner M, Zimmermann AK, Wild PJ et al (2013) TP53 mutations are common in all subtypes of epithelial ovarian cancer and occur concomitantly with KRAS mutations in the mucinous type. Exp Mol Pathol 95(2):235–241. https://doi.org/10.1016/j.yexmp.2013.08.004
Ren J, Chen Y, Song H, Chen L, Wang R (2013) Inhibition of ZEB1 reverses EMT and chemoresistance in docetaxel-resistant human lung adenocarcinoma cell line. J Cell Biochem 114(6):1395–1403. https://doi.org/10.1002/jcb.24481
Ren YA, Mullany LK, Liu Z, Herron AJ, Wong KK, Richards JS (2016) Mutant p53 promotes epithelial ovarian cancer by regulating tumor differentiation, metastasis, and responsiveness to steroid hormones. Cancer Res 76(8):2206–2218
Reyes HD, Thiel KW, Carlson MJ et al (2014) Comprehensive profiling of EGFR/HER receptors for personalized treatment of gynecologic cancers. Mol Diagn Ther 18(2):137–151. https://doi.org/10.1007/s40291-013-0070-3
Reyners AK, de Munck L, Erdkamp FL et al (2012) A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study. Ann Oncol 23(11):2896–2902. https://doi.org/10.1093/annonc/mds107
Ribas A, Wolchok JD (2018) Cancer immunotherapy using checkpoint blockade. Science 359(6382):1350–1355. https://doi.org/10.1126/science.aar4060
Rizzo A, Napoli A, Roggiani F, Tomassetti A, Bagnoli M, Mezzanzanica D (2018) One-carbon metabolism: biological players in epithelial ovarian cancer. Int J Mol Sci 19(7):2092. https://doi.org/10.3390/ijms19072092
Roggiani F, Mezzanzanica D, Rea K, Tomassetti A (2016) Guidance of signaling activations by cadherins and integrins in epithelial ovarian cancer cells. Int J Mol Sci 17(9):1387. https://doi.org/10.3390/ijms17091387
Rubinsak LA, Cohen C, Khanna N et al (2018) Folate receptor alpha expression in platinum resistant/refractory ovarian carcinomas and primary endocervical adenocarcinomas. Appl Immunohistochem Mol Morphol 26(8):567–572. https://doi.org/10.1097/PAI.0000000000000476
Ruscito I, Bellati F, Ray-Coquard I, Mirza MR, du Bois A, Gasparri ML, Costanzi F, De Marco MP, Nuti M, Caserta D, Pignata S, Dorigo O, Sehouli J, Braicu EI (2020) Incorporating parp-inhibitors in primary and recurrent ovarian cancer: a meta-analysis of 12 phase II/III randomized controlled trials. Cancer Treat Rev 87:102040. https://doi.org/10.1016/j.ctrv.2020.102040
Russell SE, McCluggage WG (2004) A multistep model for ovarian tumorigenesis: the value of mutation analysis in the KRAS and BRAF genes. J Pathol 203(2):617–619
Russo A, Czarnecki AA, Dean M et al (2018) PTEN loss in the fallopian tube induces hyperplasia and ovarian tumor formation. Oncogene 37(15):1976–1990. https://doi.org/10.1038/s41388-017-0097-8
Sakata J, Kajiyama H, Suzuki S et al (2017) Impact of positive ZEB1 expression in patients with epithelial ovarian carcinoma as an oncologic outcome-predicting indicator. Oncol Lett 14(4):4287–4293. https://doi.org/10.3892/ol.2017.6658
Saleh T, Carpenter VJ, Bloukh S, Gewirtz DA (2020) Targeting tumor cell senescence and polyploidy as potential therapeutic strategies. Semin Cancer Biol. S1044-579X(20)30270-4. https://doi.org/10.1016/j.semcancer.2020.12.010
Salmena L, Shaw P, Fans I et al (2015) Prognostic value of INPP4B protein immunohistochemistry in ovarian cancer. Eur J Gynaecol Oncol 36(3):260–267
Sarker D, Ang JE, Baird R et al (2014) First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors. Clin Cancer Res 21(1):77–86
Sato H, Niimi A, Yasuhara T, Permata TBM, Hagiwara Y, Isono M, Nuryadi E, Sekine R, Oike T, Kakoti S, Yoshimoto Y, Held KD, Suzuki Y, Kono K, Miyagawa K, Nakano T, Shibata A (2017) DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells. Nat Commun 8(1):1751. https://doi.org/10.1038/s41467-017-01883-9
Sawada K, Mitra AK, Radjabi AR et al (2008) Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res 68(7):2329–2339
Scaranti M, Cojocaru E, Banerjee S, Banerji U (2020) Exploiting the folate receptor α in oncology. Nat Rev Clin Oncol 17(6):349–359. https://doi.org/10.1038/s41571-020-0339-5
Scheid AD, Beadnell TC, Welch DR (2021) Roles of mitochondria in the hallmarks of metastasis. Br J Cancer 124(1):124–135. https://doi.org/10.1038/s41416-020-01125-8
Schnell U, Cirulli V, Giepmans BN (2013) EpCAM: structure and function in health and disease. Biochim Biophys Acta 1828(8):1989–2001. https://doi.org/10.1016/j.bbamem.2013.04.018
Seagle BL, Yang CP, Eng KH, Dandapani M, Odunsi-Akanji O, Goldberg GL, Odunsi K, Horwitz SB, Shahabi S (2015) TP53 hot spot mutations in ovarian cancer: selective resistance to microtubule stabilizers in vitro and differential survival outcomes from The Cancer Genome Atlas. Gynecol Oncol 138(1):159–164. https://doi.org/10.1016/j.ygyno.2015.04.039
Semaan A, Munkarah AR, Arabi H, Bandyopadhyay S, Seward S, Kumar S, Qazi A, Hussein Y, Morris RT, Ali-Fehmi R (2011) Expression of GLUT-1 in epithelial ovarian carcinoma: correlation with tumor cell proliferation, angiogenesis, survival and ability to predict optimal cytoreduction. Gynecol Oncol 121(1):181–186. https://doi.org/10.1016/j.ygyno.2010.11.019
Shahbazi MN, Perez-Moreno M (2015) Connections between cadherin-catenin proteins, spindle misorientation, and cancer. Tissue Barriers 3(3):e1045684. https://doi.org/10.1080/21688370.2015.1045684
Shamir ER, Ewald AJ (2015) Adhesion in mammary development: novel roles for E-cadherin in individual and collective cell migration. Curr Top Dev Biol 112:353–382
Shang AQ, Wu J, Bi F et al (2017a) Relationship between HER2 and JAK/STAT-SOCS3 signaling pathway and clinicopathological features and prognosis of ovarian cancer. Cancer Biol Ther 18(5):314–322
Shang Y, He J, Wang Y, Feng Q, Zhang Y, Guo J, Li J, Li S, Wang Y, Yan G, Ren F, Shi Y, Xu J, Zeps N, Zhai Y, He D, Chang Z (2017b) CHIP/Stub1 regulates the Warburg effect by promoting degradation of PKM2 in ovarian carcinoma. Oncogene 36(29):4191–4200. https://doi.org/10.1038/onc.2017.31
Shen W, Li HL, Liu L, Cheng JX (2017) Expression levels of PTEN, HIF-1α, and VEGF as prognostic factors in ovarian cancer. Eur Rev Med Pharmacol Sci 21(11):2596–2603
Sheppard KE, Cullinane C, Hannan KM et al (2013) Synergistic inhibition of ovarian cancer cell growth by combining selective PI3K/mTOR and RAS/ERK pathway inhibitors. Eur J Cancer 49(18):3936–3944. https://doi.org/10.1016/j.ejca.2013.08.007
Sherr CJ, McCormick F (2002) The RB and p53 pathways in cancer. Cancer Cell 2(2):103–112
Shibuya Y, Tokunaga H, Saito S et al (2018) Identification of somatic genetic alterations in ovarian clear cell carcinoma with next generation sequencing. Genes Chromosomes Cancer 57(2):51–60. https://doi.org/10.1002/gcc.22507
Shimogai R, Kigawa J, Itamochi H, Iba T, Kanamori Y, Oishi T, Shimada M, Sato S, Kawaguchi W, Sato S, Terakawa N (2008) Expression of hypoxia-inducible factor 1alpha gene affects the outcome in patients with ovarian cancer. Int J Gynecol Cancer 18(3):499–505. https://doi.org/10.1111/j.1525-1438.2007.01055.x
Sigismund S, Avanzato D, Lanzetti L (2017) Emerging functions of the EGFR in cancer. Mol Oncol 12(1):3–20
Sikora E, Czarnecka-Herok J, Bojko A, Sunderland P (2020) Therapy-induced polyploidization and senescence: coincidence or interconnection? Semin Cancer Biol. S1044-579X(20)30253-4. https://doi.org/10.1016/j.semcancer.2020.11.015
Silwal-Pandit L, Langerød A, Børresen-Dale AL (2017) TP53 mutations in breast and ovarian cancer. Cold Spring Harb Perspect Med 7(1):a026252. https://doi.org/10.1101/cshperspect.a026252
Simeone P, Trerotola M, Franck J et al (2018) The multiverse nature of epithelial to mesenchymal transition. Semin Cancer Biol. S1044-579X(18)30086-5. https://doi.org/10.1016/j.semcancer.2018.11.004
Simonin K, Brotin E, Dufort S, Dutoit S, Goux D, N’diaye M, Denoyelle C, Gauduchon P, Poulain L (2009) Mcl-1 is an important determinant of the apoptotic response to the BH3-mimetic molecule HA14-1 in cisplatin-resistant ovarian carcinoma cells. Mol Cancer Ther 8(11):3162–3170. https://doi.org/10.1158/1535-7163.MCT-09-0493
Simpkins F, Jang K, Yoon H et al (2018) Dual Src and MEK inhibition decreases ovarian cancer growth and targets tumor initiating stem-like cells. Clin Cancer Res 24(19):4874–4886. https://doi.org/10.1158/1078-0432.CCR-17-3697
Singer G, Oldt R III, Cohen Y et al (2003) Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst 95(6):484–486
Singh R, Letai A, Sarosiek K (2019) Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol 20(3):175–193. https://doi.org/10.1038/s41580-018-0089-8
Skírnisdóttir I, Seidal T (2011) Prognostic impact of concomitant p53 and PTEN on outcome in early stage (FIGO I-II) epithelial ovarian cancer. Int J Gynecol Cancer 21(6):1024–1031. https://doi.org/10.1097/IGC.0b013e31821dc906
Song H, Ramus SJ, Shadforth D et al (2006) Common variants in RB1 gene and risk of invasive ovarian cancer. Cancer Res 66(20):10220–10226
Song H, Kwan SY, Izaguirre DI et al (2013) PAX2 expression in ovarian cancer. Int J Mol Sci 14(3):6090–6105. https://doi.org/10.3390/ijms14036090
Song N, Liu H, Ma X, Zhang S (2016) Placental growth factor promotes ovarian cancer cell invasion via ZEB2. Cell Physiol Biochem 38(1):351–358. https://doi.org/10.1159/000438635
Sonntag R, Giebeler N, Nevzorova YA et al (2018) Cyclin E1 and cyclin-dependent kinase 2 are critical for initiation, but not for progression of hepatocellular carcinoma. Proc Natl Acad Sci U S A 115(37):9282–9287. https://doi.org/10.1073/pnas.1807155115
Soong TR, Dinulescu DM, Xian W et al (2018) Frontiers in the pathology and pathogenesis of ovarian cancer: cancer precursors and “precursor escape”. Hematol Oncol Clin North Am 32(6):915–928. https://doi.org/10.1016/j.hoc.2018.07.013
Soong TR, Howitt BE, Horowitz N et al (2019) The fallopian tube, “precursor escape” and narrowing the knowledge gap to the origins of high-grade serous carcinoma. Gynecol Oncol 152(2):426–433. https://doi.org/10.1016/j.ygyno.2018.11.033
Soussi T (2010) The history of p53. A perfect example of the drawbacks of scientific paradigms. EMBO Rep 11(11):822–826
Spizzo G, Fong D, Wurm M et al (2011) EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis. J Clin Pathol 64(5):415–420. https://doi.org/10.1136/jcp.2011.090274
Spreafico A, Oza AM, Clarke BA et al (2017) Genotype-matched treatment for patients with advanced type I epithelial ovarian cancer (EOC). Gynecol Oncol 144(2):250–255. https://doi.org/10.1016/j.ygyno.2016.12.002
Stamelos VA, Robinson E, Redman CW, Richardson A (2013) Navitoclax augments the activity of carboplatin and paclitaxel combinations in ovarian cancer cells. Gynecol Oncol 128(2):377–382. https://doi.org/10.1016/j.ygyno.2012.11.019
Stewart D, Cristea M (2019) Antibody-drug conjugates for ovarian cancer: current clinical development. Curr Opin Obstet Gynecol 31(1):18–23. https://doi.org/10.1097/GCO.0000000000000515
Stewart ML, Tamayo P, Wilson AJ et al (2015) KRAS genomic status predicts the sensitivity of ovarian cancer cells to decitabine. Cancer Res 75(14):2897–2906
Stover EH, Howitt B, Lindeman NI et al (2016) Somatic mutations and copy number variations in cancer-associated genes in 695 ovarian cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016-20; New Orleans, LA. Philadelphia (PA): aacr. Cancer Res 76(14 Suppl):Abstract nr 95
Stover EH, Baco MB, Cohen O, Li YY, Christie EL, Bagul M, Goodale A, Lee Y, Pantel S, Rees MG, Wei G, Presser AG, Gelbard MK, Zhang W, Zervantonakis IK, Bhola PD, Ryan J, Guerriero JL, Montero J, Liang FJ, Cherniack AD, Piccioni F, Matulonis UA, Bowtell DDL, Sarosiek KA, Letai A, Garraway LA, Johannessen CM, Meyerson M (2019) Pooled genomic screens identify anti-apoptotic genes as targetable mediators of chemotherapy resistance in ovarian cancer. Mol Cancer Res 17(11):2281–2293. https://doi.org/10.1158/1541-7786.MCR-18-1243
Strickland KC, Howitt BE, Shukla SA, Rodig S, Ritterhouse LL, Liu JF, Garber JE, Chowdhury D, Wu CJ, D’Andrea AD, Matulonis UA, Konstantinopoulos PA (2016) Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget 7(12):13587–13598. https://doi.org/10.18632/oncotarget.7277
Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O’Malley DM, Kristeleit RS, Ma L, Bell-McGuinn K, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA (2017) Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol 18(1):75–87. https://doi.org/10.1016/S1470-2045(16)30559-9
Takai M, Terai Y, Kawaguchi H et al (2014) The EMT (epithelial-mesenchymal-transition)-related protein expression indicates the metastatic status and prognosis in patients with ovarian cancer. J Ovarian Res 7:76. https://doi.org/10.1186/1757-2215-7-76
Takekuma M, Wong KK, Coleman RL (2016) A long-term surviving patient with recurrent low-grade serous ovarian carcinoma treated with the MEK1/2 inhibitor, selumetinib. Gynecol Oncol Res Pract 3:5. https://doi.org/10.1186/s40661-016-0026-5
Takenaka M, Saito M, Iwakawa R et al (2015) Profiling of actionable gene alterations in ovarian cancer by targeted deep sequencing. Int J Oncol 46(6):2389–2398. https://doi.org/10.3892/ijo.2015.2951
Tamura R, Tanaka T, Akasaki Y, Murayama Y, Yoshida K, Sasaki H (2019) The role of vascular endothelial growth factor in the hypoxic and immunosuppressive tumor microenvironment: perspectives for therapeutic implications. Med Oncol 37(1):2. https://doi.org/10.1007/s12032-019-1329-2
Tan DS, Agarwal R, Kaye SB (2006) Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol 7(11):925–934. https://doi.org/10.1016/S1470-2045(06)70939-1
Tang S, Ning Q, Yang L, Mo Z, Tang S (2020) Mechanisms of immune escape in the cancer immune cycle. Int Immunopharmacol 86:106700. https://doi.org/10.1016/j.intimp.2020.106700
Taniguchi K, Karin M (2018) NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol 18(5):309–324. https://doi.org/10.1038/nri.2017.142
Tayama S, Motohara T, Narantuya D et al (2017) The impact of EpCAM expression on response to chemotherapy and clinical outcomes in patients with epithelial ovarian cancer. Oncotarget 8(27):44312–44325. https://doi.org/10.18632/oncotarget.17871
Telleria CM (2013) Repopulation of ovarian cancer cells after chemotherapy. Cancer Growth Metastasis 6:15–21. https://doi.org/10.4137/CGM.S11333
Temkin SM, Yamada SD, Fleming GF (2010) A phase I study of weekly temsirolimus and topotecan in the treatment of advanced and/or recurrent gynecologic malignancies. Gynecol Oncol 117(3):473–476. https://doi.org/10.1016/j.ygyno.2010.02.022
Teng L, Peng S et al (2015) Conditioned media from human ovarian cancer endothelial progenitor cells induces ovarian cancer cell migration by activating epithelial-to-mesenchymal transition. Cancer Gene Ther 22(11):518–523. https://doi.org/10.1038/cgt.2015.45
Teplinsky E, Muggia F (2015) EGFR and HER2: is there a role in ovarian cancer? Translat Cancer Res 4(1):107–117. https://doi.org/10.3978/j.issn.2218-676X.2015.01.01
Tew WP, Sill MW, Walker JL et al (2018) Randomized phase II trial of bevacizumab plus everolimus versus bevacizumab alone for recurrent or persistent ovarian, fallopian tube or peritoneal carcinoma: an NRG oncology/gynecologic oncology group study. Gynecol Oncol 151(2):257–263. https://doi.org/10.1016/j.ygyno.2018.08.027
Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ (2019) Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer. J Clin Oncol 37(26):2317–2328. https://doi.org/10.1200/JCO.19.01009
Tomao F, Bardhi E, Di Pinto A, Sassu CM, Biagioli E, Petrella MC, Palaia I, Muzii L, Colombo N, Panici PB (2019) Parp inhibitors as maintenance treatment in platinum sensitive recurrent ovarian cancer: an updated meta-analysis of randomized clinical trials according to BRCA mutational status. Cancer Treat Rev 80:101909. https://doi.org/10.1016/j.ctrv.2019.101909
Topatana W, Juengpanich S, Li S, Cao J, Hu J, Lee J, Suliyanto K, Ma D, Zhang B, Chen M, Cai X (2020) Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation. J Hematol Oncol 13(1):118. https://doi.org/10.1186/s13045-020-00956-5
Trabert B, Poole EM, White E et al (2018) Analgesic use and ovarian cancer risk: an analysis in the ovarian cancer cohort consortium. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djy100
Tretter JY, Schorpp K, Luxenburger E et al (2018) A high-content screen for small-molecule regulators of epithelial cell-adhesion molecule (EpCAM) cleavage yields a robust inhibitor. J Biol Chem 293(23):8994–9005. https://doi.org/10.1074/jbc.RA118.002776
Turashvili G, Grisham RN, Chiang S et al (2018) BRAFV600E mutations and immunohistochemical expression of VE1 protein in low-grade serous neoplasms of the ovary. Histopathology 73(3):438–443. https://doi.org/10.1111/his.13651
Tutlewska K, Lubinski J, Kurzawski G (2013) Germline deletions in the EPCAM gene as a cause of Lynch syndrome – literature review. Hered Cancer Clin Pract 11(1):9. https://doi.org/10.1186/1897-4287-11-9
Urbano AM (2021) Otto Warburg: the journey towards the seminal discovery of tumor cell bioenergetic reprogramming. Biochim Biophys Acta Mol Basis Dis 1867(1):165965. https://doi.org/10.1016/j.bbadis.2020.165965
Usui A, Ko SY, Barengo N, Naora H (2014) P-cadherin promotes ovarian cancer dissemination through tumor cell aggregation and tumor-peritoneum interactions. Mol Cancer Res 12(4):504–513
van Baal JOAM, van Noorden CJF, Nieuwland R et al (2018) Development of peritoneal carcinomatosis in epithelial ovarian cancer: a review. J Histochem Cytochem 66(2):67–83
Van Berckelaer C, Brouwers AJ, Peeters DJ et al (2016) Current and future role of circulating tumor cells in patients with epithelial ovarian cancer. Eur J Surg Oncol 42(12):1772–1779. https://doi.org/10.1016/j.ejso.2016.05.010
Vanhaesebroeck B, Guillermet-Guibert J, Graupera M et al (2010) The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol 11(5):329–341. https://doi.org/10.1038/nrm2882
Varga A, Piha-Paul S, Ott PA, Mehnert JM, Berton-Rigaud D, Morosky A, Yang P, Ruman J, Matei D (2019) Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: analysis of KEYNOTE-028. Gynecol Oncol 152(2):243–250. https://doi.org/10.1016/j.ygyno.2018.11.017
Veneris JT, Matulonis UA, Liu JF, Konstantinopoulos PA (2020) Choosing wisely: selecting PARP inhibitor combinations to promote anti-tumor immune responses beyond BRCA mutations. Gynecol Oncol 156(2):488–497. https://doi.org/10.1016/j.ygyno.2019.09.021
Verdoodt F, Dehlendorff C, Friis S et al (2018) Non-aspirin NSAID use and ovarian cancer mortality. Gynecol Oncol 150(2):331–337. https://doi.org/10.1016/j.ygyno.2018.06.018
Vergote I, Armstrong D, Scambia G et al (2016) A randomized, double-blind, placebo-controlled, phase III study to assess efficacy and safety of weekly farletuzumab in combination with carboplatin and taxane in patients with ovarian cancer in first platinum-sensitive relapse. J Clin Oncol 34(19):2271–2278. https://doi.org/10.1200/JCO.2015.63.2596
Vergote I, du Bois A, Floquet A, Rau J, Kim JW, Del Campo JM, Friedlander M, Pignata S, Fujiwara K, Colombo N, Mirza MR, Monk BJ, Tsibulak I, Calvert PM, Herzog TJ, Hanker LC, Meunier J, Lee JY, Bologna A, Carrasco-Alfonso MJ, Harter P (2019a) Overall survival results of AGO-OVAR16: a phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer. Gynecol Oncol 155(2):186–191. https://doi.org/10.1016/j.ygyno.2019.08.024
Vergote I, Scambia G, O’Malley DM, Van Calster B, Park SY, Del Campo JM, Meier W, Bamias A, Colombo N, Wenham RM, Covens A, Marth C, Raza Mirza M, Kroep JR, Ma H, Pickett CA, Monk BJ, TRINOVA-3/ENGOT-ov2/GOG-3001 Investigators (2019b) Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial. Lancet Oncol 20(6):862–876. https://doi.org/10.1016/S1470-2045(19)30178-0
Verma S, Bartlett CH, Schnell P et al (2016) Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: detailed safety analysis from a multicenter, randomized, placebo-controlled, phase III study (PALOMA-3). Oncologist 21(10):1165–1175
Vieira AF, Paredes J (2015) P-cadherin and the journey to cancer metastasis. Mol Cancer 14:178. https://doi.org/10.1186/s12943-015-0448-4
Vijayakumaran R, Tan KH, Miranda PJ, Haupt S, Haupt Y (2015) Regulation of mutant p53 protein expression. Front Oncol 5:284. https://doi.org/10.3389/fonc.2015.00284
Wakahashi S, Sudo T, Oka N et al (2013) VAV1 represses E-cadherin expression through the transactivation of Snail and Slug: a potential mechanism for aberrant epithelial to mesenchymal transition in human epithelial ovarian cancer. Transl Res 162(3):181–190. https://doi.org/10.1016/j.trsl.2013.06.005
Wang Y, Ma J, Shen H et al (2014) Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway. Oncol Rep 32(5):2150–2158
Wang Y, Zhang FC, Wang YJ (2015) The efficacy and safety of non-steroidal anti-inflammatory drugs in preventing the recurrence of colorectal adenoma: a meta-analysis and systematic review of randomized trials. Colorectal Dis 17(3):188–196. https://doi.org/10.1111/codi.12838
Wang D, Li C, Zhang Y et al (2016a) Combined inhibition of PI3K and PARP is effective in the treatment of ovarian cancer cells with wild-type PIK3CA genes. Gynecol Oncol 142(3):548–556
Wang Q, Wang B, Zhang YM, Wang W (2016b) The association between CDH1 promoter methylation and patients with ovarian cancer: a systematic meta-analysis. J Ovarian Res 9:23. https://doi.org/10.1186/s13048-016-0231-1
Wang S, Han H, Hu Y et al (2017a) SLC3A2, antigen of mAb 3G9, promotes migration and invasion by upregulating of mucins in gastric cancer. Oncotarget. 8(51):88586–88598. https://doi.org/10.18632/oncotarget.19529
Wang Q, Lou W, Di W, Wu X (2017b) Prognostic value of tumor PD-L1 expression combined with CD8+ tumor infiltrating lymphocytes in high grade serous ovarian cancer. Int Immunopharmacol 52:7–14. https://doi.org/10.1016/j.intimp.2017.08.017
Wang YP, Wang QY, Li CH, Li XW (2018) COX-2 inhibition by celecoxib in epithelial ovarian cancer attenuates E-cadherin suppression through reduced Snail nuclear translocation. Chem Biol Interact 292:24–29. https://doi.org/10.1016/j.cbi.2018.06.020
Wang Y, Wei Z, Pan K, Li J, Chen Q (2020) The function and mechanism of ferroptosis in cancer. Apoptosis 25(11–12):786–798. https://doi.org/10.1007/s10495-020-01638-w
Warburg O (1930) The metabolism of tumours: investigations from the Kaiser Wilhelm Institute for Biology, Berlin-Dahlem. Arnold Constable, London
Warburg O (1956) On respiratory impairment in cancer cells. Science 124(3215):269–270
Webb JR, Milne K, Kroeger DR, Nelson BH (2016) PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer. Gynecol Oncol 141(2):293–302. https://doi.org/10.1016/j.ygyno.2016.03.008
Welch DR, Hurst DR (2019) Defining the hallmarks of metastasis. Cancer Res 79(12):3011–3027. https://doi.org/10.1158/0008-5472.CAN-19-0458
Wendel JRH, Wang X, Hawkins SM (2018) The endometriotic tumor microenvironment in ovarian cancer. Cancers (Basel) 10(8):261. https://doi.org/10.3390/cancers10080261
Westin SN, Kristeleit RS, Coleman RL et al (2019) Abstract CT158: athena (GOG-3020/ENGOT-ov45): a randomized, double-blind, placebo-controlled, Phase III study of rucaparib + nivolumab following front-line platinum-based chemotherapy in ovarian cancer. Cancer Res 79:CT158
Wojnarowicz PM, Oros KK, Quinn MC et al (2012) The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome. PLoS One 7(9):e45484
Wong KK, Tsang YT, Deavers MT et al (2010) BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas. Am J Pathol 177(4):1611–1617
Wong M, Tan N, Zha J, Peale FV, Yue P, Fairbrother WJ, Belmont LD (2012) Navitoclax (ABT-263) reduces Bcl-x(L)-mediated chemoresistance in ovarian cancer models. Mol Cancer Ther 11(4):1026–1035. https://doi.org/10.1158/1535-7163.MCT-11-0693
Wong KK, Izaguirre DI, Kwan SY et al (2013) Poor survival with wild-type TP53 ovarian cancer? Gynecol Oncol 130(3):565–569
Wong SHM, Fang CM, Chuah LH et al (2018) E-cadherin: its dysregulation in carcinogenesis and clinical implications. Crit Rev Oncol Hematol 121:11–22. https://doi.org/10.1016/j.critrevonc.2017.11.010
Wood DJ, Endicott JA (2018) Structural insights into the functional diversity of the CDK-cyclin family. Open Biol 8(9):180112
Woopen H, Pietzner K, Richter R et al (2014) Overexpression of the epithelial cell adhesion molecule is associated with a more favorable prognosis and response to platinum-based chemotherapy in ovarian cancer. J Gynecol Oncol 25(3):221–228. https://doi.org/10.3802/jgo.2014.25.3.221
Wu DI, Liu L, Ren C et al (2016) Epithelial-mesenchymal interconversions and the regulatory function of the ZEB family during the development and progression of ovarian cancer. Oncol Lett 11(2):1463–1468. https://doi.org/10.3892/ol.2016.4092
Wyld L, Bellantuono I, Tchkonia T, Morgan J, Turner O, Foss F, George J, Danson S, Kirkland JL (2020) Senescence and cancer: a review of clinical implications of senescence and senotherapies. Cancers (Basel) 12(8):2134. https://doi.org/10.3390/cancers12082134
Xu Y, Bi R, Xiao Y et al (2017) Low frequency of BRAF and KRAS mutations in Chinese patients with low-grade serous carcinoma of the ovary. Diagn Pathol 12(1):87. https://doi.org/10.1186/s13000-017-0679-3
Xu Y, Zhang Q, Miao C et al (2019) CCNG1 (Cyclin G1) regulation by mutant-P53 via induction of Notch3 expression promotes high-grade serous ovarian cancer (HGSOC) tumorigenesis and progression. Cancer Med 8(1):351–362
Yahyazadeh Mashhadi SM, Kazemimanesh M, Arashkia A et al (2019) Shedding light on the EpCAM: an overview. J Cell Physiol 234(8):12569–12580. https://doi.org/10.1002/jcp.28132
Yan Z, Tian X, Wang R et al (2017) Title prognosis significance of ZEB2 and TGF-β1 as well as other clinical characteristics in epithelial ovarian cancer. Int J Gynecol Cancer 27(7):1343–1349. https://doi.org/10.1097/IGC.0000000000001037
Yang SYC, Lheureux S, Karakasis K et al (2018) Landscape of genomic alterations in high-grade serous ovarian cancer from exceptional long- and short-term survivors. Genome Med 10(1):81. https://doi.org/10.1186/s13073-018-0590-x
Yaswen P, MacKenzie KL, Keith WN, Hentosh P, Rodier F, Zhu J, Firestone GL, Matheu A, Carnero A, Bilsland A, Sundin T, Honoki K, Fujii H, Georgakilas AG, Amedei A, Amin A, Helferich B, Boosani CS, Guha G, Ciriolo MR, Chen S, Mohammed SI, Azmi AS, Bhakta D, Halicka D, Niccolai E, Aquilano K, Ashraf SS, Nowsheen S, Yang X (2015) Therapeutic targeting of replicative immortality. Semin Cancer Biol 35(Suppl):S104–S128. https://doi.org/10.1016/j.semcancer.2015.03.007
Yeh AC, Ramaswamy S (2015) Mechanisms of cancer cell dormancy–another hallmark of cancer? Cancer Res 75(23):5014–5022. https://doi.org/10.1158/0008-5472.CAN-15-1370
Yeku O, Zamarin D, Gallagher J, Aghajanian C, Konner J (2018) A phase II trial of TPIV200 (a polypeptide vaccine against folate receptor alpha) plus durvalumab (anti-PD-L1 antibody) in patients with platinum-resistant ovarian cancer. Gynecol Oncol 149(Suppl):56–57. https://doi.org/10.1016/j.ygyno.2018.04.124
Yeung TL, Leung CS, Yip KP, Au Yeung CL, Wong ST, Mok SC (2015) Cellular and molecular processes in ovarian cancer metastasis. A review in the theme: cell and molecular processes in cancer metastasis. Am J Physiol Cell Physiol 309(7):C444–C456. https://doi.org/10.1152/ajpcell.00188.2015
Yigit S, Demir L, Tarhan MO, Cabuk FK, Ellidokuz H, Erten C, Somali I, Dirican A, Cakalagaoglu F (2012) The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma. Neoplasma 59(5):475–485. https://doi.org/10.4149/neo_2012_061
Yokoyama T, Kohn EC, Brill E, Lee JM (2017) Apoptosis is augmented in high-grade serous ovarian cancer by the combined inhibition of Bcl-2/Bcl-xL and PARP. Int J Oncol 50(4):1064–1074. https://doi.org/10.3892/ijo.2017.3914
Yoshihara K, Tajima A, Komata D et al (2009) Gene expression profiling of advanced-stage serous ovarian cancers distinguishes novel subclasses and implicates ZEB2 in tumor progression and prognosis. Cancer Sci 100(8):1421–1428. https://doi.org/10.1111/j.1349-7006.2009.01204.x
Yu L, Deng L, Li J, Zhang Y, Hu L (2013) The prognostic value of vascular endothelial growth factor in ovarian cancer: a systematic review and meta-analysis. Gynecol Oncol 128(2):391–396. https://doi.org/10.1016/j.ygyno.2012.11.002
Yu L, Hua X, Yang Y et al (2017) An updated meta-analysis of the prognostic value of decreased E-cadherin expression in ovarian cancer. Oncotarget 8(46):81176–81185. https://doi.org/10.18632/oncotarget.20885
Zamarin D, Walderich S, Holland A, Zhou Q, Iasonos AE, Torrisi JM, Merghoub T, Chesebrough LF, Mcdonnell AS, Gallagher JM, Li Y, Hollmann TJ, Grisham RN, Erskine CL, Block MS, Knutson KL, O’Cearbhaill RE, Aghajanian C, Konner JA (2020a) Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial. J Immunother Cancer 8(1):e000829. https://doi.org/10.1136/jitc-2020-000829
Zamarin D, Burger RA, Sill MW, Powell DJ Jr, Lankes HA, Feldman MD, Zivanovic O, Gunderson C, Ko E, Mathews C, Sharma S, Hagemann AR, Khleif S, Aghajanian C (2020b) Randomized phase II trial of nivolumab versus nivolumab and ipilimumab for recurrent or persistent ovarian cancer: an NRG oncology study. J Clin Oncol 38(16):1814–1823. https://doi.org/10.1200/JCO.19.02059
Zannoni GF, Improta G, Chiarello G et al (2014) Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian carcinoma. Virchows Arch 465(2):193–198. https://doi.org/10.1007/s00428-014-1599-1
Zannoni GF, Improta G, Pettinato A et al (2016) Molecular status of PI3KCA, KRAS and BRAF in ovarian clear cell carcinoma: an analysis of 63 patients. J Clin Pathol 69(12):1088–1092. https://doi.org/10.1136/jclinpath-2016-203776
Zhang GN, Liu H, Huang JM, Wang L, Zhao JS, Li C, Mi K, Zhu Y, Cheng J, Zha X (2014) TP53 K351N mutation-associated platinum resistance after neoadjuvant chemotherapy in patients with advanced ovarian cancer. Gynecol Oncol 132(3):752–757. https://doi.org/10.1016/j.ygyno.2014.01.028
Zhang D, Bai B, Xi Y et al (2016a) Can aspirin reduce the risk of endometrial cancer? A systematic review and meta-analysis of observational studies. Int J Gynecol Cancer 26(6):1111–1120. https://doi.org/10.1097/IGC.0000000000000731
Zhang X, Liu J, Liang X et al (2016b) History and progression of Fat cadherins in health and disease. Onco Targets Ther 9:7337–7343. https://doi.org/10.2147/OTT.S111176
Zhang M, Zhuang G, Sun X et al (2017) TP53 mutation-mediated genomic instability induces the evolution of chemoresistance and recurrence in epithelial ovarian cancer. Diagn Pathol 12(1):16. https://doi.org/10.1186/s13000-017-0605-8
Zhang B, Wang L, Zhao X, Wei Y, Zhang Y (2018) Identification of candidate genes associated with chemotherapy resistance in ovarian cancer. Ann Clin Lab Sci 48(5):573–579
Zhang X, Yan K, Deng L, Liang J, Liang H, Feng D, Ling B (2019a) Cyclooxygenase 2 promotes proliferation and invasion in ovarian cancer cells via the PGE2/NF-κB pathway. Cell Transplant 28(1 Suppl):1S–13S. https://doi.org/10.1177/0963689719890597
Zhang Y, Xu L, Li A, Han X (2019b) The roles of ZEB1 in tumorigenic progression and epigenetic modifications. Biomed Pharmacother 110:400–408. https://doi.org/10.1016/j.biopha.2018.11.112
Zhang L, Chen Y, Li F, Bao L, Liu W (2019c) Atezolizumab and bevacizumab attenuate cisplatin resistant ovarian cancer cells progression synergistically via suppressing epithelial-mesenchymal transition. Front Immunol 10:867. https://doi.org/10.3389/fimmu.2019.00867
Zhao R, Diop-Bove N, Visentin M, Goldman ID (2011) Mechanisms of membrane transport of folates into cells and across epithelia. Annu Rev Nutr 31:177–201
Zhao H, Wang J, Zhang Y et al (2018) Prognostic values of CCNE1 amplification and overexpression in cancer patients: a systematic review and meta-analysis. J Cancer 9(13):2397–2407. https://doi.org/10.7150/jca.24179
Zhou Y, Zheng X, Lu J, Chen W, Li X, Zhao L (2018) Ginsenoside 20(S)-Rg3 inhibits the Warburg effect via modulating DNMT3A/MiR-532-3p/HK2 pathway in ovarian cancer cells. Cell Physiol Biochem 45(6):2548–2559. https://doi.org/10.1159/000488273
Zsiros E, Lynam S, Attwood KM, Wang C, Chilakapati S, Gomez EC, Liu S, Akers S, Lele S, Frederick PJ, Odunsi K (2020) Efficacy and safety of pembrolizumab in combination with bevacizumab and oral metronomic cyclophosphamide in the treatment of recurrent ovarian cancer: a phase 2 nonrandomized clinical trial. JAMA Oncol 7:e205945. https://doi.org/10.1001/jamaoncol.2020.5945
Authors’ Contribution
KE wrote the first draft and coordinated the development of the chapter and shared a preliminary content discussion. OA revised the manuscript and SA supervised the chapter writing. The final draft was reviewed and approved by all the authors. The contents of the chapter reflect the authors’ perspectives and not of their institutions of affiliation.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
El Bairi, K., Al Jarroudi, O., Afqir, S. (2021). The Hallmarks of Ovarian Cancer: Actionable Genetics, Targetable Pathways, and Predictive Biomarkers. In: El Bairi, K. (eds) Ovarian Cancer Biomarkers. Springer, Singapore. https://doi.org/10.1007/978-981-16-1873-4_3
Download citation
DOI: https://doi.org/10.1007/978-981-16-1873-4_3
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-16-1872-7
Online ISBN: 978-981-16-1873-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)