Abstract
Angiogenesis has been identified as a hallmark of cancer. Thus, anti-angiogenic targeting has been evaluated in cancer. Colorectal cancer is one of the entities where this therapeutic principal has been most successfully introduced into the daily care of patients. Today, several anti-angiogenic drugs are approved in all lines of metastasized colorectal cancer (mCRC). In adjuvant settings, anti-angiogenic treatment did not show any benefit. In summary, still overall the benefit from anti-angiogenic treatment is modest and the identification of specific patient subgroups benefiting from this treatment is missing. Several new drugs are in development to further improve the treatment of patients with mCRC. In addition, large efforts were made to identify predictive biomarker, but so far, none of these has entered the clinical routine. Here we present the current status of anti-angiogenic drugs in mCRC and the new drugs in development for this clinical entity.
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
Similar content being viewed by others
References
Bendell JC, Bekaii-Saab TS, Cohn AL et al (2012) Treatment patterns and clinical outcomes in patients with metastatic colorectal cancer initially treated with FOLFOX-bevacizumab or FOLFIRI-bevacizumab: results from ARIES, a bevacizumab observational cohort study. Oncologist 17:1486–1495. https://doi.org/10.1634/theoncologist.2012-0190
Bennouna J, Sastre J, Arnold D et al (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14:29–37. https://doi.org/10.1016/S1470-2045(12)70477-1
Benson AB, Kiss I, Bridgewater J et al (2016) BATON-CRC: a phase II randomized trial comparing tivozanib plus mFOLFOX6 with bevacizumab plus mFOLFOX6 in stage IV metastatic colorectal cancer. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-15-3117
Cabebe EC, Fisher GA, Sikic BI (2012) A phase I trial of vandetanib combined with capecitabine, oxaliplatin and bevacizumab for the first-line treatment of metastatic colorectal cancer. Investig New Drugs 30:1082–1087. https://doi.org/10.1007/s10637-011-9656-y
Cao Y (2009) Positive and negative modulation of angiogenesis by VEGFR1 ligands. Sci Signal 2:re1. https://doi.org/10.1126/scisignal.259re1
Cao J, Zhang J, Peng W et al (2016) A phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, -2, and -3 tyrosine kinases in Chinese patients with advanced solid tumors. Cancer Chemother Pharmacol 78:259–269. https://doi.org/10.1007/s00280-016-3069-8
Carmeliet P, Jain RK (2011) Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 10:417–427. https://doi.org/10.1038/nrd3455
Cremolini C, Loupakis F, Antoniotti C et al (2015a) FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol 16:1306–1315. https://doi.org/10.1016/S1470-2045(15)00122-9
Cremolini C, Schirripa M, Antoniotti C et al (2015b) First-line chemotherapy for mCRC—a review and evidence-based algorithm. Nat Rev Clin Oncol 12:607–619. https://doi.org/10.1038/nrclinonc.2015.129
Cunningham D, Láng I, Marcuello E et al (2013a) Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 14:1077–1085. https://doi.org/10.1016/S1470-2045(13)70154-2
Cunningham D, Wong RPW, D'Haens G et al (2013b) Cediranib with mFOLFOX6 vs bevacizumab with mFOLFOX6 in previously treated metastatic colorectal cancer. Br J Cancer 108:493–502. https://doi.org/10.1038/bjc.2012.545
Díaz-Rubio E, Gómez-España A, Massuti B et al (2012) First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. Oncologist 17:15–25. https://doi.org/10.1634/theoncologist.2011-0249
Douillard JY, Cunningham D, Roth AD et al (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355:1041–1047
Falcone A, Ricci S, Brunetti I et al (2007) Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 25:1670–1676. https://doi.org/10.1200/JCO.2006.09.0928
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J et al (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374–1403. https://doi.org/10.1016/j.ejca.2012.12.027
Folprecht G, Pericay C, Saunders MP et al (2016) Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study. Ann Oncol 27:1273–1279. https://doi.org/10.1093/annonc/mdw176
Fontanella C, Ongaro E, Bolzonello S et al (2014) Clinical advances in the development of novel VEGFR2 inhibitors. Ann Transl Med 2:123. https://doi.org/10.3978/j.issn.2305-5839.2014.08.14
Gaya A, Tse V (2012) A preclinical and clinical review of aflibercept for the management of cancer. Cancer Treat Rev 38:484–493. https://doi.org/10.1016/j.ctrv.2011.12.008
Giampieri R, Caporale M, Pietrantonio F et al (2016) Second-line angiogenesis inhibition in metastatic colorectal cancer patients: straightforward or overcrowded? Crit Rev Oncol Hematol 100:99–106. https://doi.org/10.1016/j.critrevonc.2016.02.005
Giantonio BJ, Catalano PJ, Meropol NJ et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544. https://doi.org/10.1200/JCO.2006.09.6305
Goel S, Wong AH-K, Jain RK (2012) Vascular normalization as a therapeutic strategy for malignant and nonmalignant disease. Cold Spring Harb Perspect Med 2:a006486. https://doi.org/10.1101/cshperspect.a006486
de Gramont A, Figer A, Seymour M et al (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938–2947
Grothey A, Sugrue MM, Purdie DM et al (2008) Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol 26:5326–5334. https://doi.org/10.1200/JCO.2008.16.3212
Grothey A, Van Cutsem E, Sobrero A et al (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381:303–312. https://doi.org/10.1016/S0140-6736(12)61900-X
Gruenberger T, Bridgewater J, Chau I, Garcia Alfonso P et al (2015) Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol 26:702–708. https://doi.org/10.1093/annonc/mdu580
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70. https://doi.org/10.1016/S0092-8674(00)81683-9
Hecht JR, Trarbach T, Hainsworth JD et al (2011) Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma. J Clin Oncol 29:1997–2003. https://doi.org/10.1200/JCO.2010.29.4496
Hegewisch-Becker S, Graeven U, Lerchenmüller CA et al (2015) Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 16:1355–1369. https://doi.org/10.1016/S1470-2045(15)00042-X
Heldin C-H (2013) Targeting the PDGF signaling pathway in tumor treatment. Cell Commun Signal 11:97. https://doi.org/10.1186/1478-811X-11-97
Hochster HS, Grothey A, Hart L et al (2014) Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT. Ann Oncol 25:1172–1178. https://doi.org/10.1093/annonc/mdu107
Hoff PM, Hochhaus A, Pestalozzi BC et al (2012) Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, phase III study (HORIZON II). J Clin Oncol 30:3596–3603. https://doi.org/10.1200/JCO.2012.42.6031
Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342. https://doi.org/10.1056/NEJMoa032691
Iwamoto S, Takahashi T, Tamagawa H et al (2015) FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study. Ann Oncol 26:1427–1433. https://doi.org/10.1093/annonc/mdv197
Kabbinavar F, Hurwitz HI, Fehrenbacher L et al (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21:60–65
Kabbinavar FF, Schulz J, McCleod M et al (2005) Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 23:3697–3705. https://doi.org/10.1200/JCO.2005.05.112
Li J, Qin S, Xu R et al (2015a) Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 16:619–629. https://doi.org/10.1016/S1470-2045(15)70156-7
Li J, Xu R, Bai Y et al (2015b) A randomized, double-blind, placebo-controlled, multicenter phase II clinical trial of fruquintinib in patients with metastatic colorectal cancer (mCRC). Eur J Cancer 51:S366
Loupakis F, Cremolini C, Masi G et al (2014) Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 371:1609–1618. https://doi.org/10.1056/NEJMoa1403108
Maisonpierre PC, Suri C, Jones PF et al (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60
Masi G, Loupakis F, Salvatore L et al (2010) Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Lancet Oncol 11:845–852. https://doi.org/10.1016/S1470-2045(10)70175-3
Masi G, Salvatore L, Boni L et al (2015) Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial. Ann Oncol 26:724–730. https://doi.org/10.1093/annonc/mdv012
Meyerhardt JA, Ancukiewicz M, Abrams TA et al (2012) Phase I study of cetuximab, irinotecan, and vandetanib (ZD6474) as therapy for patients with previously treated metastastic colorectal cancer. PLoS One 7:e38231. https://doi.org/10.1371/journal.pone.0038231
Nakamura Y, Tanaka F, Yoshikawa Y et al (2008) PDGF-BB is a novel prognostic factor in colorectal cancer. Ann Surg Oncol 15:2129–2136. https://doi.org/10.1245/s10434-008-9943-9
Oldenhuis CN, Loos WJ, Esteves B et al (2015) A phase Ib study of the VEGF receptor tyrosine kinase inhibitor tivozanib and modified FOLFOX-6 in patients with advanced gastrointestinal malignancies. Clin Colorectal Cancer 14:18–24.e1. https://doi.org/10.1016/j.clcc.2014.12.001
O'Neil BH, Cainap C, Van Cutsem E et al (2014) Randomized phase II open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer. Clin Colorectal Cancer 13:156–163.e2. https://doi.org/10.1016/j.clcc.2014.04.001
Passardi A, Nanni O, Tassinari D et al (2015) Effectiveness of bevacizumab added to standard chemotherapy in metastatic colorectal cancer: final results for first-line treatment from the ITACa randomized clinical trial. Ann Oncol 26:1201–1207. https://doi.org/10.1093/annonc/mdv130
Peeters M, Strickland AH, Lichinitser M et al (2013) A randomised, double-blind, placebo-controlled phase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma. Br J Cancer 108:503–511. https://doi.org/10.1038/bjc.2012.594
Price TJ et al (2012) Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: a subgroup analysis from the AGITG MAX trial: an international randomised controlled trial of Capecitabine, Bevacizumab and Mitomycin C. Ann Oncol 23:1531–1536
Saltz LB, Cox JV, Blanke C et al (2000) Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan study group. N Engl J Med 343:905–914. https://doi.org/10.1056/NEJM200009283431302
Saltz LB, Clarke S, Díaz-Rubio E et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019. https://doi.org/10.1200/JCO.2007.14.9930
Satoh T, Yamaguchi K, Boku N et al (2012) Phase I results from a two-part phase I/II study of cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer. Investig New Drugs 30:1511–1518. https://doi.org/10.1007/s10637-011-9693-6
Schmoll H-J, Cunningham D, Sobrero A et al (2012) Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment for patients with advanced colorectal cancer: a double-blind, randomized phase III study (HORIZON III). J Clin Oncol 30:3588–3595. https://doi.org/10.1200/JCO.2012.42.5355
Siegel R, Desantis C, Jemal A (2014) Colorectal cancer statistics, 2014. CA Cancer J Clin 64:104–117. https://doi.org/10.3322/caac.21220
Simkens LHJ, van Tinteren H, May A et al (2015) Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet 385:1843–1852. https://doi.org/10.1016/S0140-6736(14)62004-3
Siu LL, Shapiro JD, Jonker DJ et al (2013) Phase III randomized, placebo-controlled study of cetuximab plus brivanib alaninate versus cetuximab plus placebo in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal carcinoma: the NCIC Clinical Trials Group and AGITG CO.20 trial. J Clin Oncol 31:2477–2484. https://doi.org/10.1200/JCO.2012.46.0543
Sobrero AF, Bruzzi P (2011) Vatalanib in advanced colorectal cancer: two studies with identical results. J Clin Oncol 29:1938–1940. https://doi.org/10.1200/JCO.2010.33.2429
Spratlin JL, Cohen RB, Eadens M et al (2010) Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 28:780–787. https://doi.org/10.1200/JCO.2009.23.7537
Tabernero J, Van Cutsem E, Lakomy R et al (2014) Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer 50:320–331. https://doi.org/10.1016/j.ejca.2013.09.013
Tabernero J, Yoshino T, Cohn AL et al (2015) Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol 16:499–508. https://doi.org/10.1016/S1470-2045(15)70127-0
Tampellini M, Sonetto C, Scagliotti GV (2016) Novel anti-angiogenic therapeutic strategies in colorectal cancer. Expert Opin Investig Drugs 25:507–520. https://doi.org/10.1517/13543784.2016.1161754
Tang PA, Cohen SJ, Kollmannsberger C et al (2012) Phase II clinical and pharmacokinetic study of aflibercept in patients with previously treated metastatic colorectal cancer. Clin Cancer Res 18:6023–6031. https://doi.org/10.1158/1078-0432.CCR-11-3252
Tebbutt NC, Wilson K, Gebski VJ et al (2010) Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol 28:3191–3198. https://doi.org/10.1200/JCO.2009.27.7723
Tebbutt N, Kotasek D, Burris HA et al (2015) Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. Cancer Chemother Pharmacol 75:993–1004. https://doi.org/10.1007/s00280-015-2694-y
Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108. https://doi.org/10.3322/caac.21262
Tournigand C, Chibaudel B, Samson B et al (2015) Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial. Lancet Oncol 16:1493–1505. https://doi.org/10.1016/S1470-2045(15)00216-8
Tung JJ, Tattersall IW, Kitajewski J (2012) Tips, stalks, tubes: notch-mediated cell fate determination and mechanisms of tubulogenesis during angiogenesis. Cold Spring Harb Perspect Med 2:a006601. https://doi.org/10.1101/cshperspect.a006601
Van Cutsem E, Twelves C, Cassidy J et al (2001) Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19:4097–4106
Van Cutsem E, Bajetta E, Valle J et al (2011) Randomized, placebo-controlled, phase III study of oxaliplatin, fluorouracil, and leucovorin with or without PTK787/ZK 222584 in patients with previously treated metastatic colorectal adenocarcinoma. J Clin Oncol 29:2004–2010. https://doi.org/10.1200/JCO.2010.29.5436
Van Cutsem E, Tabernero J, Lakomy R et al (2012) Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30:3499–3506. https://doi.org/10.1200/JCO.2012.42.8201
Van Cutsem E, Khayat D, Verslype C et al (2013) Phase I dose-escalation study of intravenous aflibercept administered in combination with irinotecan, 5-fluorouracil and leucovorin in patients with advanced solid tumours. Eur J Cancer 49:17–24. https://doi.org/10.1016/j.ejca.2012.07.007
Van Cutsem E, Prenen H, D'Haens G et al (2015) A phase I/II, open-label, randomised study of nintedanib plus mFOLFOX6 versus bevacizumab plus mFOLFOX6 in first-line metastatic colorectal cancer patients. Ann Oncol 26:2085–2091. https://doi.org/10.1093/annonc/mdv286
Van Cutsem E, Cervantes A, Adam R et al (2016a) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 27:1386–1422. https://doi.org/10.1093/annonc/mdw235
Van Cutsem E, Joulain F, Hoff PM et al (2016b) Aflibercept plus FOLFIRI vs. placebo plus FOLFIRI in second-line metastatic colorectal cancer: a post hoc analysis of survival from the phase III VELOUR study subsequent to exclusion of patients who had recurrence during or within 6 months of completing adjuvant Oxaliplatin-based therapy. Target Oncol 11:383–400. https://doi.org/10.1007/s11523-015-0402-9
Van Cutsem E, Yoshino T, Hocke J et al (2016c) Rationale and design for the LUME-Colon 1 study: a randomized, double-blind, placebo-controlled phase III trial of Nintedanib plus best supportive care versus placebo plus best supportive Care in Patients with advanced colorectal cancer refractory to standard treatment. Clin Colorectal Cancer 15:91–94.e1. https://doi.org/10.1016/j.clcc.2015.09.005
Van de Veire S, Stalmans I, Heindryckx F et al (2010) Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease. Cell 141:178–190. https://doi.org/10.1016/j.cell.2010.02.039
Willett CG, Boucher Y, di Tomaso E et al (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10:145–147. https://doi.org/10.1038/nm988
Winkler F, Kozin SV, Tong RT et al (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553–563. https://doi.org/10.1016/j.ccr.2004.10.011
Wong R, Cunningham D, Barbachano Y et al (2011) A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection. Ann Oncol 22:2042–2048. https://doi.org/10.1093/annonc/mdq714
Xu R, Shen L, Wang K et al (2015) A randomized, double-blind, parallel-group, placebo-controlled, multicenter, phase II clinical study of famitinib in the treatment of advanced metastatic colorectal cancer. J Clin Oncol 33:513
Yao J, Wu X, Zhuang G et al (2011) Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy. Proc Natl Acad Sci USA 108:11590–11595. https://doi.org/10.1073/pnas.1109029108
Zhou A, Zhang W, Chang C et al (2013) Phase I study of the safety, pharmacokinetics and antitumor activity of famitinib. Cancer Chemother Pharmacol 72:1043–1053. https://doi.org/10.1007/s00280-013-2282-y
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this entry
Cite this entry
Zander, T., Goede, V., Hallek, M. (2019). Anti-angiogenic Targeting in Metastatic Colorectal Cancer Therapy. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-33673-2_16
Download citation
DOI: https://doi.org/10.1007/978-3-319-33673-2_16
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-33671-8
Online ISBN: 978-3-319-33673-2
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences