Skip to main content

Advertisement

SpringerLink
Log in

Clinical trials and future potential of targeted therapy for ovarian cancer

  • Review Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage with a poor prognosis. Currently, surgical tumor debulking followed by chemotherapy based on platinum and taxane is the standard treatment for advanced disease. However, these patients remain at great risk for recurrence and developing drug resistance. Therefore, new treatment strategies are needed to improve outcomes for patients with advanced and recurrent ovarian cancer. Several agents targeted at particular molecules have been developed for ovarian cancer and are now entering clinical trials. The functional targets of these agents are aberrations in tumor tissues including angiogenesis, the human epidermal growth factor receptor family, poly(ADP-ribose) polymerase (PARP), mammalian target of rapamycin (mTOR) signaling pathway, and α-folate receptor (α-FR). The anti-angiogenic compound bevacizumab has been reported as the most effective targeted agent. Bevacizumab plus chemotherapy prolonged progression-free survival (PFS) both for advanced and platinum-sensitive recurrent ovarian cancer, but did not increase overall survival. A PARP inhibitor, olaparib, applied as maintenance treatment also improved PFS in platinum-sensitive relapsed ovarian cancer. Furthermore, mTOR inhibitors and a monoclonal antibody to α-FR, farletuzumab, are attractive treatment strategies either alone or combined with chemotherapy. Understanding the tumor molecular biology and identifying predictive biomarkers are essential steps in selecting the best treatment strategies. This article reviews available clinical data on the most promising targeted agents for ovarian cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Heintz AP, Odicino F, Maisonneuve P et al (2006) Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet 95(Suppl 1):S161–S192

    Google Scholar 

  2. Bristow RE, Tomacruz RS, Armstrong DK et al (2002) Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 20:1248–1259

    Article  PubMed  Google Scholar 

  3. Markman M, Markman J, Webster K et al (2004) Duration of response to second-line, platinum-based chemotherapy for ovarian cancer: implications for patient management and clinical trial design. J Clin Oncol 22:3120–3125

    Article  PubMed  CAS  Google Scholar 

  4. Agarwal R, Kaye SB (2003) Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer 3:502–516

    Article  PubMed  CAS  Google Scholar 

  5. Ma WW, Adjei AA (2009) Novel agents on the horizon for cancer therapy. CA Cancer J Clin 59:111–137

    Article  PubMed  Google Scholar 

  6. Itamochi H (2010) Targeted therapies in epithelial ovarian cancer: molecular mechanisms of action. World J Biol Chem 1:209–220

    Article  PubMed  Google Scholar 

  7. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    Article  PubMed  CAS  Google Scholar 

  8. Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364

    Article  PubMed  CAS  Google Scholar 

  9. Brown MR, Blanchette JO, Kohn EC (2000) Angiogenesis in ovarian cancer. Baillieres Best Pract Res Clin Obstet Gynaecol 14:901–918

    Article  PubMed  CAS  Google Scholar 

  10. Shimogai R, Kigawa J, Itamochi H et al (2008) Expression of hypoxia-inducible factor 1alpha gene affects the outcome in patients with ovarian cancer. Int J Gynecol Cancer 18:499–505

    Article  PubMed  CAS  Google Scholar 

  11. Klasa-Mazurkiewicz D, Jarzab M, Milczek T et al (2011) Clinical significance of VEGFR-2 and VEGFR-3 expression in ovarian cancer patients. Pol J Pathol 62:31–40

    PubMed  CAS  Google Scholar 

  12. Siddiqui GK, Maclean AB, Elmasry K et al (2011) Immunohistochemical expression of VEGF predicts response to platinum based chemotherapy in patients with epithelial ovarian cancer. Angiogenesis 14:155–161

    Article  PubMed  CAS  Google Scholar 

  13. Burger RA, Sill MW, Monk BJ et al (2007) Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol 25:5165–5171

    Article  PubMed  CAS  Google Scholar 

  14. Cannistra SA, Matulonis UA, Penson RT et al (2007) Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 25:5180–5186

    Article  PubMed  CAS  Google Scholar 

  15. Matulonis UA, Berlin S, Ivy P et al (2009) Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol 27:5601–5606

    Article  PubMed  CAS  Google Scholar 

  16. Biagi JJ, Oza AM, Chalchal HI et al (2011) A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC Clinical Trials Group Study. Ann Oncol 22:335–340

    Article  PubMed  CAS  Google Scholar 

  17. Baumann KH, du Bois A, Meier W et al (2012) A phase II trial (AGO 2.11) in platinum-resistant ovarian cancer: a randomized multicenter trial with sunitinib (SU11248) to evaluate dosage, schedule, tolerability, toxicity and effectiveness of a multitargeted receptor tyrosine kinase inhibitor monotherapy. Ann Oncol. doi:10.1093/annonc/mds003

  18. Matei D, Sill MW, Lankes HA et al (2011) Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis: a gynecologic oncology group trial. J Clin Oncol 29:69–75

    Article  PubMed  Google Scholar 

  19. Bodnar L, Gornas M, Szczylik C (2011) Sorafenib as a third line therapy in patients with epithelial ovarian cancer or primary peritoneal cancer: a phase II study. Gynecol Oncol 123:33–36

    Article  PubMed  CAS  Google Scholar 

  20. Annunziata CM, Walker AJ, Minasian L et al (2010) Vandetanib, designed to inhibit VEGFR2 and EGFR signaling, had no clinical activity as monotherapy for recurrent ovarian cancer and no detectable modulation of VEGFR2. Clin Cancer Res 16:664–672

    Article  PubMed  CAS  Google Scholar 

  21. Friedlander M, Hancock KC, Rischin D et al (2010) A phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol 119:32–37

    Article  PubMed  CAS  Google Scholar 

  22. Coleman RL, Broaddus RR, Bodurka DC et al (2006) Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant epithelial ovarian and primary peritoneal cancers. Gynecol Oncol 101:126–131

    Article  PubMed  CAS  Google Scholar 

  23. Schilder RJ, Sill MW, Lee RB et al (2008) Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 26:3418–3425

    Article  PubMed  CAS  Google Scholar 

  24. Posadas EM, Kwitkowski V, Kotz HL et al (2007) A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a phase II clinical study with proteomic profiling. Cancer 110:309–317

    Article  PubMed  CAS  Google Scholar 

  25. Alberts DS, Liu PY, Wilczynski SP et al (2007) Phase II trial of imatinib mesylate in recurrent, biomarker positive, ovarian cancer (Southwest Oncology Group Protocol S0211). Int J Gynecol Cancer 17:784–788

    Article  PubMed  CAS  Google Scholar 

  26. Noguera IR, Sun CC, Broaddus RR et al (2012) Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant low-grade serous carcinoma of the ovary, peritoneum, or fallopian tube. Gynecol Oncol 125:640–645

    Article  PubMed  CAS  Google Scholar 

  27. Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 8:579–591

    Article  PubMed  CAS  Google Scholar 

  28. Kim KJ, Li B, Houck K et al (1992) The vascular endothelial growth factor proteins: identification of biologically relevant regions by neutralizing monoclonal antibodies. Growth Factors 7:53–64

    Article  PubMed  CAS  Google Scholar 

  29. Kim KJ, Li B, Winer J et al (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841–844

    Article  PubMed  CAS  Google Scholar 

  30. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62

    Article  PubMed  CAS  Google Scholar 

  31. Micha JP, Goldstein BH, Rettenmaier MA et al (2007) A phase II study of outpatient first-line paclitaxel, carboplatin, and bevacizumab for advanced-stage epithelial ovarian, peritoneal, and fallopian tube cancer. Int J Gynecol Cancer 17:771–776

    Article  PubMed  CAS  Google Scholar 

  32. Penson RT, Dizon DS, Cannistra SA et al (2010) Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors. J Clin Oncol 28:154–159

    Article  PubMed  CAS  Google Scholar 

  33. Burger RA, Brady MF, Bookman MA et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365:2473–2483

    Article  PubMed  CAS  Google Scholar 

  34. Perren TJ, Swart AM, Pfisterer J et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365:2484–2496

    Article  PubMed  CAS  Google Scholar 

  35. Aghajanian C, Blank SV, Goff BA et al (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 30:2039–2045

    Google Scholar 

  36. Pujade-Lauraine E, Hilpert F, Weber B et al (2012) AURELIA: a randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC). J Clin Oncol 30:LBA5002

    Google Scholar 

  37. Heckman CA, Holopainen T, Wirzenius M et al (2008) The tyrosine kinase inhibitor cediranib blocks ligand-induced vascular endothelial growth factor receptor-3 activity and lymphangiogenesis. Cancer Res 68:4754–4762

    Article  PubMed  CAS  Google Scholar 

  38. Wedge SR, Kendrew J, Hennequin LF et al (2005) AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res 65:4389–4400

    Article  PubMed  CAS  Google Scholar 

  39. Sonpavde G, Hutson TE (2007) Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep 9:115–119

    Article  PubMed  CAS  Google Scholar 

  40. Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358:1160–1174

    Article  PubMed  CAS  Google Scholar 

  41. Lafky JM, Wilken JA, Baron AT et al (2008) Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer. Biochim Biophys Acta 1785:232–265

    PubMed  CAS  Google Scholar 

  42. Moyer JD, Barbacci EG, Iwata KK et al (1997) Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res 57:4838–4848

    PubMed  CAS  Google Scholar 

  43. Gordon AN, Finkler N, Edwards RP et al (2005) Efficacy and safety of erlotinib HCl, an epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor, in patients with advanced ovarian carcinoma: results from a phase II multicenter study. Int J Gynecol Cancer 15:785–792

    Article  PubMed  CAS  Google Scholar 

  44. Vergote IB, Joly F, Katsaros D et al (2012) Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a GCIG and EORTC-GCG study. J Clin Oncol 30:LBA5000

    Google Scholar 

  45. Franklin MC, Carey KD, Vajdos FF et al (2004) Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 5:317–328

    Article  PubMed  CAS  Google Scholar 

  46. Gordon MS, Matei D, Aghajanian C et al (2006) Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: potential predictive relationship with tumor HER2 activation status. J Clin Oncol 24:4324–4332

    Article  PubMed  CAS  Google Scholar 

  47. Makhija S, Amler LC, Glenn D et al (2010) Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. J Clin Oncol 28:1215–1223

    Article  PubMed  CAS  Google Scholar 

  48. Bookman MA, Darcy KM, Clarke-Pearson D et al (2003) Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol 21:283–290

    Article  PubMed  CAS  Google Scholar 

  49. Campos S, Hamid O, Seiden MV et al (2005) Multicenter, randomized phase II trial of oral CI-1033 for previously treated advanced ovarian cancer. J Clin Oncol 23:5597–5604

    Article  PubMed  CAS  Google Scholar 

  50. Garcia AA, Sill MW, Lankes HA et al (2012) A phase II evaluation of lapatinib in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a gynecologic oncology group study. Gynecol Oncol 124:569–574

    Article  PubMed  CAS  Google Scholar 

  51. Schilder RJ, Sill MW, Chen X et al (2005) Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a Gynecologic Oncology Group Study. Clin Cancer Res 11:5539–5548

    Article  PubMed  CAS  Google Scholar 

  52. Posadas EM, Liel MS, Kwitkowski V et al (2007) A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer. Cancer 109:1323–1330

    Article  PubMed  CAS  Google Scholar 

  53. Schilder RJ, Pathak HB, Lokshin AE et al (2009) Phase II trial of single agent cetuximab in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with the potential for dose escalation to rash. Gynecol Oncol 113:21–27

    Article  PubMed  CAS  Google Scholar 

  54. Seiden MV, Burris HA, Matulonis U et al (2007) A phase II trial of EMD72000 (matuzumab), a humanized anti-EGFR monoclonal antibody, in patients with platinum-resistant ovarian and primary peritoneal malignancies. Gynecol Oncol 104:727–731

    Article  PubMed  CAS  Google Scholar 

  55. 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 123:19–26

    Article  PubMed  CAS  Google Scholar 

  56. Aghajanian C, Blessing JA, Darcy KM et al (2009) A phase II evaluation of bortezomib in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecol Oncol 115:215–220

    Article  PubMed  CAS  Google Scholar 

  57. Audeh MW, Carmichael J, Penson RT et al (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 376:245–251

    Article  PubMed  CAS  Google Scholar 

  58. Gelmon KA, Tischkowitz M, Mackay H et al (2011) Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol 12:852–861

    Article  PubMed  CAS  Google Scholar 

  59. Kaye SB, Lubinski J, Matulonis U et al (2012) Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J Clin Oncol 30:372–379

    Article  PubMed  CAS  Google Scholar 

  60. Modesitt SC, Sill M, Hoffman JS et al (2008) A phase II study of vorinostat in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 109:182–186

    Article  PubMed  CAS  Google Scholar 

  61. Mackay HJ, Hirte H, Colgan T et al (2010) Phase II trial of the histone deacetylase inhibitor belinostat in women with platinum resistant epithelial ovarian cancer and micropapillary (LMP) ovarian tumours. Eur J Cancer 46:1573–1579

    Article  PubMed  CAS  Google Scholar 

  62. Bell-McGuinn KM, Matthews CM, Ho SN et al (2011) A phase II, single-arm study of the anti-alpha5beta1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer. Gynecol Oncol 121:273–279

    Article  PubMed  CAS  Google Scholar 

  63. Usha L, Sill MW, Darcy KM et al (2011) A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies. Gynecol Oncol 121:455–461

    Article  PubMed  CAS  Google Scholar 

  64. 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 123:27–32

    Article  PubMed  CAS  Google Scholar 

  65. Gold MA, Brady WE, Lankes HA et al (2012) A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 125:635–639

    Article  PubMed  CAS  Google Scholar 

  66. Rouleau M, Patel A, Hendzel MJ et al (2010) PARP inhibition: PARP1 and beyond. Nat Rev Cancer 10:293–301

    Article  PubMed  CAS  Google Scholar 

  67. Press JZ, De Luca A, Boyd N et al (2008) Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities. BMC Cancer 8:17

    Article  PubMed  Google Scholar 

  68. The Cancer Genome Atlas Research Network (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474:609–615

    Article  Google Scholar 

  69. Konstantinopoulos PA, Spentzos D, Karlan BY et al (2010) Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. J Clin Oncol 28:3555–3561

    Article  PubMed  CAS  Google Scholar 

  70. Weberpals JI, Clark-Knowles KV, Vanderhyden BC (2008) Sporadic epithelial ovarian cancer: clinical relevance of BRCA1 inhibition in the DNA damage and repair pathway. J Clin Oncol 26:3259–3267

    Article  PubMed  CAS  Google Scholar 

  71. Ledermann J, Harter P, Gourley C et al (2012) Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366:1382–1392

    Article  PubMed  CAS  Google Scholar 

  72. Bellacosa A, de Feo D, Godwin AK et al (1995) Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int J Cancer 64:280–285

    Article  PubMed  CAS  Google Scholar 

  73. Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2:489–501

    Article  PubMed  CAS  Google Scholar 

  74. Altomare DA, Wang HQ, Skele KL et al (2004) AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth. Oncogene 23:5853–5857

    Article  PubMed  CAS  Google Scholar 

  75. Kelemen LE (2006) The role of folate receptor alpha in cancer development, progression and treatment: cause, consequence or innocent bystander? Int J Cancer 119:243–250

    Article  PubMed  CAS  Google Scholar 

  76. Elnakat H, Ratnam M (2006) Role of folate receptor genes in reproduction and related cancers. Front Biosci 11:506–519

    Article  PubMed  CAS  Google Scholar 

  77. Kalli KR, Oberg AL, Keeney GL et al (2008) Folate receptor alpha as a tumor target in epithelial ovarian cancer. Gynecol Oncol 108:619–626

    Article  PubMed  CAS  Google Scholar 

  78. 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 6:360–369

    Article  PubMed  CAS  Google Scholar 

  79. Toffoli G, Cernigoi C, Russo A et al (1997) Overexpression of folate binding protein in ovarian cancers. Int J Cancer 74:193–198

    Article  PubMed  CAS  Google Scholar 

  80. Bottero F, Tomassetti A, Canevari S et al (1993) Gene transfection and expression of the ovarian carcinoma marker folate binding protein on NIH/3T3 cells increases cell growth in vitro and in vivo. Cancer Res 53:5791–5796

    PubMed  CAS  Google Scholar 

  81. Ebel W, Routhier EL, Foley B et al (2007) Preclinical evaluation of MORAb-003, a humanized monoclonal antibody antagonizing folate receptor-alpha. Cancer Immun 7:6

    PubMed  Google Scholar 

  82. Konner JA, Bell-McGuinn KM, Sabbatini P et al (2010) Farletuzumab, a humanized monoclonal antibody against folate receptor alpha, in epithelial ovarian cancer: a phase I study. Clin Cancer Res 16:5288–5295

    Article  PubMed  CAS  Google Scholar 

  83. Meinhold-Heerlein I, Bauerschlag D, Hilpert F et al (2005) Molecular and prognostic distinction between serous ovarian carcinomas of varying grade and malignant potential. Oncogene 24:1053–1065

    Article  PubMed  CAS  Google Scholar 

  84. Schmeler KM, Gershenson DM (2008) Low-grade serous ovarian cancer: a unique disease. Curr Oncol Rep 10:519–523

    Article  PubMed  Google Scholar 

  85. Hsu CY, Bristow R, Cha MS et al (2004) Characterization of active mitogen-activated protein kinase in ovarian serous carcinomas. Clin Cancer Res 10:6432–6436

    Article  PubMed  CAS  Google Scholar 

  86. Jones S, Wang TL, Kurman RJ et al (2012) Low-grade serous carcinomas of the ovary contain very few point mutations. J Pathol 226:413–420

    Article  PubMed  CAS  Google Scholar 

  87. Romero I, Bast RC Jr (2012) Minireview: human ovarian cancer: biology, current management, and paths to personalizing therapy. Endocrinology 153:1593–1602

    Article  PubMed  CAS  Google Scholar 

  88. Farley J, Brady W, Birrer M et al (2012) A phase II trial of selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum. Annual meeting of AACR CT-05

  89. Campbell IG, Russell SE, Choong DY et al (2004) Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 64:7678–7681

    Article  PubMed  CAS  Google Scholar 

  90. Willner J, Wurz K, Allison KH et al (2007) Alternate molecular genetic pathways in ovarian carcinomas of common histological types. Hum Pathol 38:607–613

    Article  PubMed  CAS  Google Scholar 

  91. Kuo KT, Mao TL, Jones S et al (2009) Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol 174:1597–1601

    Article  PubMed  CAS  Google Scholar 

  92. Obata K, Morland SJ, Watson RH et al (1998) Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res 58:2095–2097

    PubMed  CAS  Google Scholar 

  93. Gamallo C, Palacios J, Moreno G et al (1999) Beta-catenin expression pattern in stage I and II ovarian carcinomas : relationship with beta-catenin gene mutations, clinicopathological features, and clinical outcome. Am J Pathol 155:527–536

    Article  PubMed  CAS  Google Scholar 

  94. Ichikawa Y, Nishida M, Suzuki H et al (1994) Mutation of K-ras protooncogene is associated with histological subtypes in human mucinous ovarian tumors. Cancer Res 54:33–35

    PubMed  CAS  Google Scholar 

  95. Gemignani ML, Schlaerth AC, Bogomolniy F et al (2003) Role of KRAS and BRAF gene mutations in mucinous ovarian carcinoma. Gynecol Oncol 90:378–381

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishicho, Yonago, 683-8504, Japan

    Hiroaki Itamochi

  2. Tottori University Hospital Cancer Center, 36-1 Nishicho, Yonago, 683-8504, Japan

    Junzo Kigawa

Authors
  1. Hiroaki Itamochi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Junzo Kigawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroaki Itamochi.

About this article

Cite this article

Itamochi, H., Kigawa, J. Clinical trials and future potential of targeted therapy for ovarian cancer. Int J Clin Oncol 17, 430–440 (2012). https://doi.org/10.1007/s10147-012-0459-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-012-0459-8

Keywords

Search

Navigation