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VEGF Ligands

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Cancer Therapeutic Targets

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Abstract

Vascular endothelial growth factor (VEGF) is a family of key regulator of vasculogenesis and angiogenesis in physiology and pathology. The main clinical target and mediator of tumor angiogenesis is VEGF-A. Targeting VEGF in cancer has been a step forward in the realization of a new anticancer strategy aiming at cutting off resources to tumors instead of direct attack on tumor cells. In the present chapter we summarized the biology of VEGF as target, focusing on mechanisms leading to cancer related neoangiogenesis. We also described the most effectively developed anti-VEGF strategies for cancer treatment and possible diagnostic, prognostic, and predictive markers. Despite many improvements for cancer treatment have been achieved thanks to the adoption of VEGF as target, no predictive or prognostic VEGF-related biomarkers have been identified so far. Up to date no clues are available in order to identify patients for whom VEGF levels normalization might be beneficial. Mechanisms of resistance to treatment, both primary or after treatment are still under investigation.

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References

  • Ah-See ML, Makris A, Taylor NJ, Harrison M, Richman PI, Burcombe RJ, et al. Early changes in functional dynamic magnetic resonance imaging predict for pathologic response to neoadjuvant chemotherapy in primary breast cancer. Clin Cancer Res. 2008;14(20):6580–9.

    Article  CAS  PubMed  Google Scholar 

  • Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2001;166(1):678–89.

    Article  CAS  PubMed  Google Scholar 

  • Aprile G, Rijavec E, Fontanella C, Rihawi K, Grossi F. Ramucirumab: preclinical research and clinical development. OncoTargets Ther. 2014;7:1997–2006.

    Article  CAS  Google Scholar 

  • Baluk P, Hashizume H, McDonald DM. Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev. 2005;15(1):102–11.

    Article  CAS  PubMed  Google Scholar 

  • Bautz F, Rafii S, Kanz L, Mohle R. Expression and secretion of vascular endothelial growth factor-A by cytokine-stimulated hematopoietic progenitor cells. Possible role in the hematopoietic microenvironment. Exp Hematol. 2000;28(6):700–6.

    Article  CAS  PubMed  Google Scholar 

  • Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer. 2008;8(8):592–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broxmeyer HE, Cooper S, Li ZH, Lu L, Song HY, Kwon BS, et al. Myeloid progenitor cell regulatory effects of vascular endothelial cell growth factor. Int J Hematol. 1995;62(4):203–15.

    Article  CAS  PubMed  Google Scholar 

  • Burstein HJ, Chen YH, Parker LM, Savoie J, Younger J, Kuter I, et al. VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res. 2008;14(23):7871–7.

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov. 2011;10(6):417–27.

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380(6573):435–9.

    Article  CAS  PubMed  Google Scholar 

  • Chaudhary B, Khaled YS, Ammori BJ, Elkord E. Neuropilin 1: function and therapeutic potential in cancer. Cancer Immunol Immunother. 2014;63(2):81–99.

    Article  CAS  PubMed  Google Scholar 

  • Chauhan VP, Stylianopoulos T, Martin JD, Popovic Z, Chen O, Kamoun WS, et al. Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. Nat Nanotechnol. 2012;7(6):383–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1814–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chung AS, Ferrara N. Developmental and pathological angiogenesis. Annu Rev Cell Dev Biol. 2011;27:563–84.

    Article  CAS  PubMed  Google Scholar 

  • de Langen AJ, van den Boogaart V, Lubberink M, Backes WH, Marcus JT, van Tinteren H, et al. Monitoring response to antiangiogenic therapy in non-small cell lung cancer using imaging markers derived from PET and dynamic contrast-enhanced MRI. J Nucl Med. 2011;52(1):48–55.

    Article  PubMed  Google Scholar 

  • Deprimo SE, Bello CL, Smeraglia J, Baum CM, Spinella D, Rini BI, et al. Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins. J Transl Med. 2007;5:32.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009;15(3):232–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elisei R, Schlumberger MJ, Muller SP, Schoffski P, Brose MS, Shah MH, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013;31(29):3639–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008;8(8):579–91.

    Article  CAS  PubMed  Google Scholar 

  • Ferrara N. Binding to the extracellular matrix and proteolytic processing: two key mechanisms regulating vascular endothelial growth factor action. Mol Biol Cell. 2010;21(5):687–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 1996;380(6573):439–42.

    Article  CAS  PubMed  Google Scholar 

  • Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev. 2004;3(5):391–400.

    CAS  Google Scholar 

  • Ferrarotto R, Hoff PM. Antiangiogenic drugs for colorectal cancer: exploring new possibilities. Clin Colorectal Cancer. 2013;12(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  • Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31–9.

    Article  CAS  PubMed  Google Scholar 

  • Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med. 1996;2(10):1096–103.

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Donas J, Rodriguez-Antona C, Jonasch E. Molecular markers to predict response to therapy. Semin Oncol. 2013;40(4):444–58.

    Article  CAS  PubMed  Google Scholar 

  • Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665–73.

    Article  CAS  PubMed  Google Scholar 

  • Gerger A, El-Khoueiry A, Zhang W, Yang D, Singh H, Bohanes P, et al. Pharmacogenetic angiogenesis profiling for first-line bevacizumab plus oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Clin Cancer Res. 2011;17(17):5783–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gianni L, Romieu GH, Lichinitser M, Serrano SV, Mansutti M, Pivot X, et al. AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013;31(14):1719–25.

    Article  CAS  PubMed  Google Scholar 

  • Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303–12.

    Article  CAS  PubMed  Google Scholar 

  • Grunewald M, Avraham I, Dor Y, Bachar-Lustig E, Itin A, Jung S, et al. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell. 2006;124(1):175–89.

    Article  CAS  PubMed  Google Scholar 

  • Gullberg M, Gustafsdottir SM, Schallmeiner E, Jarvius J, Bjarnegard M, Betsholtz C, et al. Cytokine detection by antibody-based proximity ligation. Proc Natl Acad Sci U S A. 2004;101(22):8420–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  • Hegde PS, Jubb AM, Chen D, Li NF, Meng YG, Bernaards C, et al. Predictive impact of circulating vascular endothelial growth factor in four phase III trials evaluating bevacizumab. Clin Cancer Res. 2013;19(4):929–37.

    Article  CAS  PubMed  Google Scholar 

  • Hein M, Graver S. Tumor cell response to bevacizumab single agent therapy in vitro. Cancer Cell Int. 2013;13(1):94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Y, Yuan J, Righi E, Kamoun WS, Ancukiewicz M, Nezivar J, et al. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci U S A. 2012;109(43):17561–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42.

    Article  CAS  PubMed  Google Scholar 

  • Hylton N. Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker. J Clin Oncol. 2006;24(20):3293–8.

    Article  CAS  PubMed  Google Scholar 

  • Jain RK. Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. J Clin Oncol. 2013;31(17):2205–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, Loeffler JS, et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol. 2009;6(6):327–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jayson GC. Evaluation of plasma VEGFA as a potential predictive pan-tumour biomarker for bevacizumab. Eur J Cancer. 2011;47:S96.

    Article  Google Scholar 

  • Jayson GC, Hicklin DJ, Ellis LM. Antiangiogenic therapy – evolving view based on clinical trial results. Nat Rev Clin Oncol. 2012;9(5):297–303.

    Article  CAS  PubMed  Google Scholar 

  • Junck L. Bevacizumab antiangiogenic therapy for glioblastoma. Neurology. 2011;76(5):414–5.

    Article  PubMed  Google Scholar 

  • Kamba T, McDonald DM. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer. 2007;96(12):1788–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koch S, Tugues S, Li X, Gualandi L, Claesson-Welsh L. Signal transduction by vascular endothelial growth factor receptors. Biochem J. 2011;437(2):169–83.

    Article  CAS  PubMed  Google Scholar 

  • Koch S, van Meeteren LA, Morin E, Testini C, Westrom S, Bjorkelund H, et al. NRP1 presented in trans to the endothelium arrests VEGFR2 endocytosis, preventing angiogenic signaling and tumor initiation. Dev Cell. 2014;28(6):633–46.

    Article  CAS  PubMed  Google Scholar 

  • Kubicka S, Greil R, Andre T, Bennouna J, Sastre J, Van Cutsem E, et al. Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings. Ann Oncol. 2013;24(9):2342–9.

    Article  CAS  PubMed  Google Scholar 

  • Lambrechts D, Delmar P, Miles DW, Leighl N, Saltz L, Escudier B, et al. Single nucleotide polymorphism analysis and outcome in advanced-stage cancer patients treated with bevacizumab. Eur J Cancer. 2011;47 suppl 1:1414.

    Google Scholar 

  • Lambrechts D, Lenz HJ, de Haas S, Carmeliet P, Scherer SJ. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol. 2013;31(9):1219–30.

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Jilani SM, Nikolova GV, Carpizo D, Iruela-Arispe ML. Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol. 2005;169(4):681–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S, et al. Autocrine VEGF signaling is required for vascular homeostasis. Cell. 2007;130(4):691–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lenz HJ, Tabernero J, Yoshino T, Oum’Hamed Z, Vlassak S, Sassi M, et al. LUME-Colon 1: a double-blind, randomized phase III study of nintedanib plus best supportive care (BSC) versus placebo plus BSC in patients with colorectal cancer (CRC) refractory to standard therapies. J Clin Oncol. 2015;33(Suppl 3): abstr TPS794.

    Google Scholar 

  • Liu Y, Gray NS. Rational design of inhibitors that bind to inactive kinase conformations. Nat Chem Biol. 2006;2(7):358–64.

    Article  CAS  PubMed  Google Scholar 

  • Loupakis F, Cremolini C, Yang D, Salvatore L, Zhang W, Wakatsuki T, et al. Prospective validation of candidate SNPs of VEGF/VEGFR pathway in metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab. PLoS One. 2013;8(7):e66774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maru D, Venook AP, Ellis LM. Predictive biomarkers for bevacizumab: are we there yet? Clin Cancer Res. 2013;19(11):2824–7.

    Article  CAS  PubMed  Google Scholar 

  • Miles DW, de Haas SL, Dirix LY, Romieu G, Chan A, Pivot X, et al. Biomarker results from the AVADO phase 3 trial of first-line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer. Br J Cancer. 2013;108(5):1052–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller JC, Pien HH, Sahani D, Sorensen AG, Thrall JH. Imaging angiogenesis: applications and potential for drug development. J Natl Cancer Inst. 2005;97(3):172–87.

    Article  CAS  PubMed  Google Scholar 

  • Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357(26):2666–76.

    Article  CAS  PubMed  Google Scholar 

  • Murukesh N, Dive C, Jayson GC. Biomarkers of angiogenesis and their role in the development of VEGF inhibitors. Br J Cancer. 2010;102(1):8–18.

    Article  CAS  PubMed  Google Scholar 

  • Nilsson I, Bahram F, Li X, Gualandi L, Koch S, Jarvius M, et al. VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts. EMBO J. 2010;29(8):1377–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling – in control of vascular function. Nat Rev Mol Cell Biol. 2006;7(5):359–71.

    Article  CAS  PubMed  Google Scholar 

  • Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009;15(3):220–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pander J, Wessels JA, Gelderblom H, van der Straaten T, Punt CJ, Guchelaar HJ. Pharmacogenetic interaction analysis for the efficacy of systemic treatment in metastatic colorectal cancer. Ann Oncol. 2011;22(5):1147–53.

    Article  CAS  PubMed  Google Scholar 

  • Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014;15(2):143–55.

    Article  CAS  PubMed  Google Scholar 

  • Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931–9.

    Article  CAS  PubMed  Google Scholar 

  • Roybal JD, Zang Y, Ahn YH, Yang Y, Gibbons DL, Baird BN, et al. miR-200 Inhibits lung adenocarcinoma cell invasion and metastasis by targeting Flt1/VEGFR1. Mol Cancer Res. 2011;9(1):25–35.

    Article  CAS  PubMed  Google Scholar 

  • Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542–50.

    Article  CAS  PubMed  Google Scholar 

  • Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008;26(28):4672–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219(4587):983–5.

    Article  CAS  PubMed  Google Scholar 

  • Sessa C, Guibal A, Del Conte G, Ruegg C. Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations? Nat Clin Pract Oncol. 2008;5(7):378–91.

    Article  CAS  PubMed  Google Scholar 

  • Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer. 2011;2(12):1097–105.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992;359(6398):843–5.

    Article  CAS  PubMed  Google Scholar 

  • Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, 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 3 study. Lancet Oncol. 2015;16(5):499–508.

    Article  CAS  PubMed  Google Scholar 

  • Tammela T, Zarkada G, Wallgard E, Murtomaki A, Suchting S, Wirzenius M, et al. Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. Nature. 2008;454(7204):656–60.

    Article  CAS  PubMed  Google Scholar 

  • Tirumani SH, Fairchild A, Krajewski KM, Nishino M, Howard SA, Baheti AD, et al. Anti-VEGF molecular targeted therapies in common solid malignancies: comprehensive update for radiologists. Radiographics. 2015;35(2):455–74.

    Article  PubMed  Google Scholar 

  • Van Cutsem E, de Haas S, Kang YK, Ohtsu A, Tebbutt NC, Ming Xu J, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol. 2012a;30(17):2119–27.

    Article  PubMed  Google Scholar 

  • Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausova J, Macarulla T, 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. 2012b;30(28):3499–506.

    Article  PubMed  Google Scholar 

  • Vernes JM, Meng YG. Detection and quantification of VEGF isoforms by ELISA. Methods Mol Biol. 2015;1332:25–37.

    Article  PubMed  Google Scholar 

  • Wells Jr SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30(2):134–41.

    Article  CAS  PubMed  Google Scholar 

  • Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224–35.

    Article  CAS  PubMed  Google Scholar 

  • Willett CG, Boucher Y, Duda DG, di Tomaso E, Munn LL, Tong RT, et al. Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol. 2005;23(31):8136–9.

    Article  PubMed  Google Scholar 

  • Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, et al. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol. 2009;27(18):3020–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell. 2004;6(6):553–63.

    CAS  PubMed  Google Scholar 

  • Wissner A, Fraser HL, Ingalls CL, Dushin RG, Floyd MB, Cheung K, et al. Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cysteine residues in the kinase domains of EGFR and VEGFR-2. Bioorg Med Chem. 2007;15(11):3635–48.

    Article  CAS  PubMed  Google Scholar 

  • Xu L, Duda DG, di Tomaso E, Ancukiewicz M, Chung DC, Lauwers GY, et al. Direct evidence that bevacizumab, an anti-VEGF antibody, up-regulates SDF1alpha, CXCR4, CXCL6, and neuropilin 1 in tumors from patients with rectal cancer. Cancer Res. 2009;69(20):7905–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang JC. Bevacizumab for patients with metastatic renal cancer: an update. Clin Cancer Res. 2004;10(18 Pt 2):6367S–70.

    Article  CAS  PubMed  Google Scholar 

  • Zhang HT, Scott PA, Morbidelli L, Peak S, Moore J, Turley H, et al. The 121 amino acid isoform of vascular endothelial growth factor is more strongly tumorigenic than other splice variants in vivo. Br J Cancer. 2000;83(1):63–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer. 2009;9(1):28–39.

    Article  PubMed  Google Scholar 

  • Zhu AX, Sahani DV, Duda DG, di Tomaso E, Ancukiewicz M, Catalano OA, et al. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol. 2009;27(18):3027–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Marta Schirripa & Heinz-Josef Lenz

  2. Department of Physiological Chemistry, Biocenter, University of Wuerzburg, Wuerzburg, Germany

    Stefan J. Scherer

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  1. Marta Schirripa
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  2. Heinz-Josef Lenz
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  3. Stefan J. Scherer
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Correspondence to Marta Schirripa , Heinz-Josef Lenz or Stefan J. Scherer .

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Editors and Affiliations

  1. Division of Hematology & Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA

    John L. Marshall

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Schirripa, M., Lenz, HJ., Scherer, S.J. (2017). VEGF Ligands. In: Marshall, J. (eds) Cancer Therapeutic Targets. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0717-2_17

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