The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls

References

• Malvezzi M, Carioli G, Bertuccio P, et al. European cancer mortality predictions for the year 2018 with focus on colorectal cancer. Ann Oncol. 2018;29:1016–1022.
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2018. CA Cancer J Clin. 2018;68:7–30.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–1422.
   PubMed Web of Science ®Google Scholar
• Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–2917.
   PubMed Web of Science ®Google Scholar
• DiPietro LA. Angiogenesis and wound repair: when enough is enough. J Leukoc Biol. 2016;100:979–984.
   PubMed Web of Science ®Google Scholar
• Folkman J. Fundamental concepts of the angiogenic process. Curr Mol Med. 2003;3:643–651.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.
   PubMed Web of Science ®Google Scholar
• Mathonnet M, Perraud A, Christou N, et al. Hallmarks in colorectal cancer: angiogenesis and cancer stem-like cells. World J Gastroenterol. 2014;20:4189–4196.
   PubMed Web of Science ®Google Scholar
• Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–676.
   PubMed Web of Science ®Google Scholar
• Lyer S, Leonidas DD, Swaminathan GJ, et al. The crystal structure of human placenta growth factor-1 (PlGF-1), an angiogenic protein, at 2.0 A resolution. J Biol Chem. 2001;276:12153–12161.
   PubMed Web of Science ®Google Scholar
• Olsson A-K, Dimberg A, Kreuger J, et al. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol. 2006;7:359–371.
   PubMed Web of Science ®Google Scholar
• Cai J, Ahmad S, Jiang WG, et al. Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells. Diabetes. 2003;52:2959–2968.
   PubMed Web of Science ®Google Scholar
• Tchaikovski V, Fellbrich G, Waltenberger J. The molecular basis of VEGFR-1 signal transduction pathways in primary human monocytes. Arterioscler. Thromb Vasc Biol. 2008;28:322–328.
   PubMed Web of Science ®Google Scholar
• List AF, Glinsmann-Gibson B, Stadheim C, et al. Vascular endothelial growth factor receptor-1 and receptor-2 initiate a phosphatidylinositide 3-kinase-dependent clonogenic response in acute myeloid leukemia cells. Exp Hematol. 2004;32:526–535.
   PubMed Web of Science ®Google Scholar
• Landgren E, Schiller P, Cao Y, et al. Placenta growth factor stimulates MAP kinase and mitogenicity but not phospholipase C-gamma and migration of endothelial cells expressing Flt 1. Oncogene. 1998;16:359–367.
   PubMed Web of Science ®Google Scholar
• Bellik L, Vinci MC, Filippi S, et al. Intracellular pathways triggered by the selective FLT-1-agonist placental growth factor in vascular smooth muscle cells exposed to hypoxia. Br J Pharmacol. 2005;146:568–575.
   PubMed Web of Science ®Google Scholar
• Hiratsuka S, Maru Y, Okada A, et al. Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis. Cancer Res. 2001;61:1207–1213.
   PubMed Web of Science ®Google Scholar
• Selvaraj SK, Giri RK, Perelman N, et al. Mechanism of monocyte activation and expression of proinflammatory cytochemokines by placenta growth factor. Blood. 2003;102:1515–1524.
   PubMed Web of Science ®Google Scholar
• Wang T-F, Lockhart AC. Aflibercept in the treatment of metastatic colorectal cancer. Clin Med Insights Oncol. 2012;6:19–30.
   PubMedGoogle Scholar
• Roodhart J, Langenberg M, Witteveen E, et al. The molecular basis of class side effects due to treatment with inhibitors of the VEGF/VEGFR pathway. Curr Clin Pharmacol. 2008;3:132–143.
   PubMedGoogle Scholar
• Koch S, Claesson-Welsh L. Signal transduction by vascular endothelial growth factor receptors. Cold Spring Harb Perspect Med. 2012;2:a006502.
   PubMed Web of Science ®Google Scholar
• Inoue T, Kibata K, Suzuki M, et al. Identification of a vascular endothelial growth factor (VEGF) antagonist, sFlt-1, from a human hematopoietic cell line NALM-16. FEBS Lett. 2000;469:14–18.
   PubMed Web of Science ®Google Scholar
• Cudmore MJ, Hewett PW, Ahmad S, et al. The role of heterodimerization between VEGFR-1 and VEGFR-2 in the regulation of endothelial cell homeostasis. Nat Commun. 2012;3:972.
   PubMed Web of Science ®Google Scholar
• Sela S, Itin A, Natanson-Yaron S, et al. A novel human-specific soluble vascular endothelial growth factor receptor 1: cell-type-specific splicing and implications to vascular endothelial growth factor homeostasis and preeclampsia. Circ Res. 2008;102:1566–1574.
   PubMed Web of Science ®Google Scholar
• Khan K, Cunningham D, Chau I. Targeting angiogenic pathways in colorectal cancer: complexities, challenges and future directions. Curr Drug Targets. 2017;18:56–71.
   PubMed Web of Science ®Google Scholar
• Karnezis T, Shayan R, Caesar C, et al. VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium. Cancer Cell. 2012;21:181–195.
   PubMed Web of Science ®Google Scholar
• Forsythe JA, Jiang BH, Iyer NV, et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996;16:4604–4613.
   PubMed Web of Science ®Google Scholar
• Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004;25:581–611.
   PubMed Web of Science ®Google Scholar
• Fischer C, Mazzone M, Jonckx B, et al. FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? Nat Rev Cancer. 2008;12:942–956.
   Google Scholar
• Li H, Jin Y, Hu Y, et al. The PLGF/c-MYC/miR-19a axis promotes metastasis and stemness in gallbladder cancer. Cancer Sci. 2018;109:1532–1544.
   PubMed Web of Science ®Google Scholar
• Wang Z, Liu T. Placental growth factor signaling regulates isoform splicing of vascular endothelial growth factor A in the control of lung cancer cell metastasis. Mol Cell Biochem. 2018;439:163–169.
   PubMed Web of Science ®Google Scholar
• Soukup V, Čapoun O, Pešl M, et al. Placental growth factor in bladder cancer compared to the diagnostic accuracy and prognostic performance of vascular endothelial growth factor A. Anticancer Res. 2018;38:239–246.
   PubMed Web of Science ®Google Scholar
• Rahbari NN, Reissfelder C, Mühlbayer M, et al. Correlation of circulating angiogenic factors with circulating tumor cells and disease recurrence in patients undergoing curative resection for colorectal liver metastases. Ann Surg Oncol. 2011;18:2182–2191.
   PubMed Web of Science ®Google Scholar
• Aktaş SH, Akbulut H, Yazici O, et al. A new angiogenesis prognostic index with VEGFA, PLGF, and angiopoietin 1 predicts survival in patients with advanced gastric cancer. Turkish J Med Sci. 2017;47:399–406.
   PubMed Web of Science ®Google Scholar
• Pagani E, Ruffini F, Cappellini GCA, et al. Placenta growth factor and neuropilin-1 collaborate in promoting melanoma aggressiveness. Int J Oncol. 2016;48:1581–1589.
   PubMed Web of Science ®Google Scholar
• Autiero M, Waltenberger J, Communi D, et al. Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med. 2003;9:936–943.
   PubMed Web of Science ®Google Scholar
• Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473:298–307.
   PubMed Web of Science ®Google Scholar
• Zoccoli A, Luliani M, Pantano F, et al. Premetastatic niche: ready for new therapeutic interventions? Expert Opin Ther Targets. 2012;16:S119–29.
   PubMed Web of Science ®Google Scholar
• Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380:435–439.
   PubMed Web of Science ®Google Scholar
• Carmeliet P, Moons L, Luttun A, et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 2001;7:575–583.
   PubMed Web of Science ®Google Scholar
• Hattori K, Heissig B, Wu Y, et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1+stem cells from bone-marrow microenvironment. Nat Med. 2002;8:841–849.
   PubMed Web of Science ®Google Scholar
• Kaplan RN, Riba RD, Zacharoulis S, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438:820–827.
   PubMed Web of Science ®Google Scholar
• Luttun A, Tjwa M, Moons L, et al. Revascularization of ischemic tissues by PLGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med. 2002;8:831–840.
   PubMed Web of Science ®Google Scholar
• Riechelmann R, Grothey A. Antiangiogenic therapy for refractory colorectal cancer: current options and future strategies. Ther Adv Med Oncol. 2017;9:106–126.
   PubMed Web of Science ®Google Scholar
• Strickler JH, Hurwitz HI. Bevacizumab-based therapies in the first-line treatment of metastatic colorectal cancer. Oncologist. 2012;17:513–524.
   PubMed Web of Science ®Google Scholar
• Giantonio BJ, Catalano PJ, Meropol NJ, et al. 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. 2007;25:1539–1544.
   PubMed Web of Science ®Google Scholar
• Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013;14:29–37.
   PubMed Web of Science ®Google Scholar
• Grothey A, Sugrue MM, Purdie DM, et al. 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. 2008;26:5326–5334.
   PubMed Web of Science ®Google Scholar
• Casanovas O, Hicklin DJ, Bergers G, et al. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell. 2005;8:299–309.
   PubMed Web of Science ®Google Scholar
• Cao Y. Positive and negative modulation of angiogenesis by VEGFR1 ligands. Sci Signal. 2009;2:re1.
   PubMed Web of Science ®Google Scholar
• Kopetz S, Hoff PM, Morris JS, et al. Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J Clin Oncol. 2010;28:453–459.
   PubMed Web of Science ®Google Scholar
• Hayashi H, Arao T, Matsumoto K, et al. Biomarkers of reactive resistance and early disease progression during chemotherapy plus bevacizumab treatment for colorectal carcinoma. Oncotarget. 2014;5:2588–2595.
   PubMedGoogle Scholar
• Horita Y, Yamada Y, Kato K, et al. Phase II clinical trial of second-line FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: AVASIRI trial. Int J Clin Oncol. 2012;17:604–609.
   PubMed Web of Science ®Google Scholar
• Loupakis F, Cremolini C, Fioravanti A, et al. Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer. Br J Cancer. 2011;104:1262–1269.
   PubMed Web of Science ®Google Scholar
• Lieu CH, Tran H, Jiang Z-Q, et al. The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer. PLoS One. 2013;8:e77117.
   PubMed Web of Science ®Google Scholar
• Fischer C, Jonckx B, Mazzone M, et al. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell. 2007;131:463–475.
   PubMed Web of Science ®Google Scholar
• Van de Veire S, Stalmans I, Heindryckx F, et al. Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease. Cell. 2010;141:178–190.
   PubMed Web of Science ®Google Scholar
• Rizzo C, Yin XY, Packman K, et al. RO5323441, a humanized monoclonal antibody against the placenta growth factor, blocks PlGF-induced VEGFR-1 phosphorylation in vitro and tumor growth in vivo. AACR. 2010;70(abstr):1370.
   Google Scholar
• Ciombor KK, Berlin J, Chan E. Aflibercept. Clin Cancer Res. 2013;19:1920–1925.
   PubMed Web of Science ®Google Scholar
• Papadopoulos N, Martin J, Ruan Q, et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012;15:171–185.
   PubMed Web of Science ®Google Scholar
• Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A. 2002;99:11393–11398.
   PubMed Web of Science ®Google Scholar
• Huang J, Frischer JS, Serur A, et al. Regression of established tumors and metastases by potent vascular endothelial growth factor blockade. Proc Natl Acad Sci U S A. 2003;100:7785–7790.
   PubMed Web of Science ®Google Scholar
• Gaya A, Tse V. A preclinical and clinical review of aflibercept for the management of cancer. Cancer Treat Rev. 2012;38:484–493.
   PubMed Web of Science ®Google Scholar
• Eichten A, Adler AP, Cooper B, et al. Rapid decrease in tumor perfusion following VEGF blockade predicts long-term tumor growth inhibition in preclinical tumor models. Angiogenesis. 2013;16:429–441.
   PubMed Web of Science ®Google Scholar
• Lassoued W, Murphy D, Tsai J, et al. Effect of VEGF and VEGF Trap on vascular endothelial cell signaling in tumors. Cancer Biol Ther. 2010;10:1326–1333.
   PubMed Web of Science ®Google Scholar
• Chiron M, Bagley RG, Pollard J, et al. Differential antitumor activity of aflibercept and bevacizumab in patient-derived xenograft models of colorectal cancer. Mol Cancer Ther. 2014;13:1636–1644.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Tabernero J, Lakomy R, et al. 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. 2012;30:3499–3506.
   PubMed Web of Science ®Google Scholar
• Ruff P, Ferry DR, Lakomy R, et al. Time course of safety and efficacy of aflibercept in combination with FOLFIRI in patients with metastatic colorectal cancer who progressed on previous oxaliplatin-based therapy. Eur J Cancer. 2015;51:18–26.
   PubMed Web of Science ®Google Scholar
• Tabernero J, Van Cutsem E, Lakomy R, et al. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analysis from the VELOUR trial. Eur J Cancer. 2014;50:320–331.
   PubMed Web of Science ®Google Scholar
• Sims TN, Gao B, Phillips R, et al. Potential predictive and prognostic biomarkers identified in baseline plasma samples from the VELOUR trial. J Clin Oncol. 2015;33(abstr):638.
   Google Scholar
• Tabernero J, Joulain F, Iqhal SU, et al. Placental growth factor and the angiogenic environment based on analysis of baseline plasma biomarkers from the VELOUR trial. J Clin Oncol. 2017;35:592.
   Web of Science ®Google Scholar
• Wirapati P, Pamella V, Vandenbosch B, et al. Velour trial biomarkers update: impact of RAS, BRAF and sideness on aflibercept activity. J Clin Oncol. 2017;35(abstr):3538.
   PubMedGoogle Scholar
• Tabernero J, Yoshino T, Cohn A, et al. 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 III study. Lancet Oncol. 2015;16:499–508.
   PubMed Web of Science ®Google Scholar
• Tabernero J, Hozak RR, Yoshino T, et al. Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study. Ann Oncol. 2018;29:602–609.
   PubMed Web of Science ®Google Scholar
• Strumberg D, Schultheis B. Regorafenib for cancer. Expert Opin Investig Drugs. 2012;21:879–889.
   PubMed Web of Science ®Google Scholar
• Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase III trial. Lancet. 2013;381:303–312.
   PubMed Web of Science ®Google Scholar
• Mata Velasco E, González-Flores E, Juez Martel I, et al. In the pathway to response: is aflibercept an optimal treatment for RASwt mCRC patients after progression to 1st line containing anti-EGFR? Ann Oncol. 2018;29(abst):478P.
   Google Scholar