Skip to main content
SpringerLink
Log in

Anti-Angiogenic Cancer Therapy: Development of Resistance

  • Living reference work entry
  • First Online:
Tumor Angiogenesis

  • 230 Accesses

Abstract

Therapeutic resistance is the major cause for a poor prognosis in cancer patients. Clinical results of anti-angiogenic therapies are very modest, resulting in a moderate improvement of overall survival, and the clinical outcome is associated with the development of resistance. The clinical benefit of anti-angiogenic drugs is due to several intrinsic and acquired limitations including tumor indifference to anti-angiogenic therapy; selection of resistant clones and activation of alternative mechanisms that lead to activation of angiogenesis, even when the target of the drug remains inhibited; therapy-induced reduction of oxygen levels within the tumor and accumulation of infiltrating cancer stem cells; activation of pro-invasive mechanisms and increased dissemination and metastasis; normalization of tumor blood vessels; recruitment of inflammatory cells and immature myeloid cells; alternative mechanisms of tumor vessel formation; and genomic instability of tumor endothelial cells. In this context, the concept and strategies of anti-angiogenic therapies should be extensively reconsidered and reevaluated. In particular, rational combinations of anti-angiogenic agents based on pharmacokinetic and pharmacodynamics data are needed to overcome resistance.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Abramsson A, Lindblom P, Betsholtz C (2003) Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors. J Clin Invest 112:1142–1151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akiyama K, Ohga N, Hida Y et al (2012) Tumor endothelial cells acquire drug resistance by MDR-1 up-regulation via VEGF signaling in tumor microenvironment. Am J Pathol 180:1283–1293

    Article  CAS  PubMed  Google Scholar 

  • Alvero AB, Fu HH, Holmberg J et al (2009) Stem-like ovarian cancer cells can serve as tumor vascular progenitors. Stem Cells 27:2405–2413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asahara T, Takahashi T, Masuda H et al (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964–3972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Azam F, Mehta S, Harris AL (2010) Mechanisms of resistance to antiangiogenesis therapy. Eur J Cancer 46:1323–1332

    Article  CAS  PubMed  Google Scholar 

  • Batchelor TT, Sorensen AG, di Tomaso E et al (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Batchelor TT, Duda DG, di Tomaso E et al (2010) Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol 28:2817–2823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergers G, Hanahan D (2008) Modes of resistance to anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7:987–989

    Google Scholar 

  • Bergers G, Song S, Meyer-Morse N et al (2003) Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 111:1287–1295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Black WC, Welch HG (1993) Advances in diagnostic imaging and overestimation of disease prevalence and the benefits of therapy. New Engl J Med 328:1237–1243

    Article  CAS  PubMed  Google Scholar 

  • Blagosklonny MV (2001) Hypoxia-inducible factor: Achille’s heel of antiangiogenic cancer therapy (review). Int J Oncol 19:257–262

    CAS  PubMed  Google Scholar 

  • Blagosklonny MV (2004) Antiangiogenic therapy and tumor progression. Cancer Cell 5:13–17

    Article  CAS  PubMed  Google Scholar 

  • Blagosklonny MV (2005) How Avastin potentiates chemotherapeutic drugs: action and reaction in antiangiogenic therapy. Cancer Biol Ther 4:1307–1310

    Article  CAS  PubMed  Google Scholar 

  • Bussolati B, Deamabrosis I, Russo S et al (2003) Altered angiogenesis and survival in human tumor-derived endothelial cells. FASEB J 17:1159–1161

    CAS  PubMed  Google Scholar 

  • Casanovas O, Hicklin DJ, Bergers G et al (2005) Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8:299–309

    Article  CAS  PubMed  Google Scholar 

  • Ceradini DJ, Kulkarni AR, Gallaghan MJ et al (2004) Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 10:858–864

    Article  CAS  PubMed  Google Scholar 

  • Cesca M, Bizzaro F, Zucchetti M et al (2013) Tumor delivery of chemotherapy combined with inhibitors of angiogenesis and vascular targeting agents. Front Oncol 3:259

    Article  PubMed  PubMed Central  Google Scholar 

  • Chae SS, Kamoun WS, Farrar CT et al (2010) Angiopoietin-2 interferes with anti-VEGFR2-induced vessel normalization and survival benefit in mice bearing gliomas. Clin Cancer Res 16:3618–3627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chung AS, Wu X, Zhuang G et al (2013) An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy. Nat Med 19:1114–1123

    Article  CAS  PubMed  Google Scholar 

  • Cooke VG, Le Bleu VS, Keskin D et al (2012) Pericyte depletion results in hypoxia-assciated epithelial to mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell 21:66–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crawford Y, Ferrara N (2009) Tumor and stromal pathways mediating refractoriness/resistance to anti-angiogenic therapies. Trends Pharmacol Sci 30:624–630

    Article  CAS  PubMed  Google Scholar 

  • Crawford Y, Kasman I, Yu L et al (2009) PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 15:21–34

    Article  CAS  PubMed  Google Scholar 

  • Crivellato E, Nico B, Vacca A et al (2003) B-cell non-Hodgkin’s lymphomas express heterogeneous patterns of neovascularization. Haematologica 88:671–678

    PubMed  Google Scholar 

  • De Palma M, Venneri MA, Galli R et al (2005) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8:211–226

    Article  PubMed  CAS  Google Scholar 

  • Dings RP, Vang KB, Castermans K et al (2011) Enhancement of T-cell-mediated antitumor response: angiostatic adjuvant to immunotherapy against cancer. Clin Cancer Res 17:3134–3145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Djonov V, Hogger K, Sedlacek R et al (2001) MMP-19: cellular localization of a novel metalloproteinase within normal breast tissue and mammary gland tumours. J Pathol 195:147–155

    Article  CAS  PubMed  Google Scholar 

  • Ebos JM, Lee CR, Christensen JG et al (2007) Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy. Proc Natl Acad Sci USA 104:17069–17074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ebos JM, Lee CR, Cruz-Munoz W et al (2009) Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15:232–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El Hallani S, Boisselier B, Peglion F et al (2010) A new alternative mechanism in glioblastoma vascularization: tubular vasculogenic mimicry. Brain 133:973–982

    Article  PubMed  PubMed Central  Google Scholar 

  • Eubank TD, Roberts RD, Khan M et al (2009) Granulocyte-macrophage colony-stimulating factor inhibits breast cancer growth and metastasis by invoking an anti-angiogenic program in tumor-educated macrophages. Cancer Res 69:2133–2140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finger EC, Giaccia AJ (2010) Hypoxia, inflammation, and the tumor microenvironment in metastatic disease. Cancer Metastasis Rev 29:285–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finke J, Ko J, Rini B et al (2011) MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy. Int Immunopharmacol 11:856–861

    Article  CAS  PubMed  Google Scholar 

  • Folkman J (1971) Tumour angiogenesis: therapeutic implications. New Engl J Med 285:1182–1186

    Article  CAS  PubMed  Google Scholar 

  • Gabrusiewicz K, Liu D, Cortes-Santiago N et al (2004) Anti-vascular endothelial growth factor-therapy-induced glioma invasion is associated with accumulation of tie-2expressing monocytes. Oncotarget 5:2208–2220

    Article  Google Scholar 

  • Gotink KJ, Verheul HM (2010) Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? Angiogenesis 13:1–14

    Article  CAS  PubMed  Google Scholar 

  • Gottesman MM (2002) Mechanisms of cancer drug resistance. Ann Rev Med 53:615–627

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Hida K, Klagsbrun M (2005) A new perspective on tumor endothelial cells: unexpected chromosome and centrosome abnormalities. Cancer Res 65:2507–2510

    Article  CAS  PubMed  Google Scholar 

  • Hida K, Hida Y, Amin DN et al (2004) Tumor-associated endothelial cells with cytogenetic abnormalities. Cancer Res 64:8249–8255

    Article  CAS  PubMed  Google Scholar 

  • Hlushchuk R, Riesterer O, Baum O et al (2008) Tumor recovery by angiogenic switch from sprouting to intussusceptive angiogenesis after treatment with PTK787/ZK222584 or ionizing radiation. Am J Pathol 173:1173–1185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holash J, Maisonpierre PC, Compton D et al (1999) Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284:1994–1998

    Article  CAS  PubMed  Google Scholar 

  • Hu Y, Jan C, Mu L et al (2015) Fibroblast-derived exosomes contribute to chemoresistance through priming cancer stem cells in Colo-rectal cancer. PLoS One 10:eo125625

    Google Scholar 

  • Huang D, Ding Y, Zhou M et al (2010) Interleukin-8 mediates resistance to antiangiogenic agent sunitinib in renal cell carcinoma. Cancer Res 70:1063–1071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New Engl J Med 350:2335–2342

    Article  CAS  PubMed  Google Scholar 

  • Inai T, Mancuso M, Hashizume H et al (2004) Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol 165:35–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7:987–989

    Article  CAS  PubMed  Google Scholar 

  • Jain RK (2013) Normalizing tumor microenvironment to treat cancer bench to bedside to biomarkers. J Clin Oncol 31:2205–2218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

  • Kuczynski EA, Yin M, Bar-Zion A et al (2016) Co-option of liver vessels and not sprouting angiogenesis drives acquired sorafenib resistance in hepatocellular carcinoma. J Nat Cancer Inst 108:djw032

    Article  Google Scholar 

  • Kuenen O, Johansson M, Oudin A et al (2011) Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Nat Acad Sci USA 108:3328–3339

    Google Scholar 

  • Kunkel P, Ulbricht U, Bohlen P et al (2001) Inhibition of glioma angiogenesis and growth in vivo by systemic treatment with a monoclonal antibody against vascular endothelial growth factor receptor-2. Cancer Res 61:6624–6628

    CAS  PubMed  Google Scholar 

  • Leenders WP, Kusters B, Verrijp K et al (2004) Antiangiogenic therapy of cerebral melanoma metastases results in sustained tumor progression via vessel co-option. Clin Cancer Res 10:6222–6230

    Article  CAS  PubMed  Google Scholar 

  • Li R, Ren M, Chen N et al (2014) Presence of intratumoral platelets is associated with tumor vessel structure and metastasis. BMC Cancer 14:167

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lockhart AC, Rothenberg ML, Dupont J et al (2010) Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol 28:207–214

    Google Scholar 

  • Lu KV, Chang JP, Parachoniak CA et al (2012) VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex. Cancer Cell 22:21–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Madden SL, Cook BP, Nacht M et al (2004) Vascular gene expression in nonneoplastic and malignant brain. Am J Pathol 165:601–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mancuso MR, Davis R, Norberg SM et al (2006) Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest 116:2610–2621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maniotis AJ, Folberg R, Hess A et al (1999) Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Markovina S, Callander NS, O’Connor SL et al (2010) Bone marrow stroma cells from multiple myeloma patients uniquely induce bortezomib resistant NF-kappa B activity in myeloma cells. Mol Cancer 9:176

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Martinez-Outschoorn UE, Goldberg A, Lin Z et al (2011) Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells. Cancer Biol Ther 12:924–938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McGee MC, Hamner JB, Williams RF et al (2010) Improved intratumoral oxygenation through vascular normalization increases glioma sensitivity to ionizing radiation. Int J Radiat Oncol Biol Phys 76:1537–1545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mignatti P, Rifkin DB (1993) Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 73:161–195

    CAS  PubMed  Google Scholar 

  • Moschetta M, Mishima Y, Sahin I et al (2014) Role of endothelial progenitor cells in cancer progression. Bichim Biophys Acta 1846:26–39

    CAS  Google Scholar 

  • Motz GT, Santoro LP, Wang T et al (2014) Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nat Med 20:607–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nico B, Crivellato E, Guidolin D et al (2010) Intussusceptive microvascular growth in human glioma. Clin Exp Med 10:93–98

    Article  CAS  PubMed  Google Scholar 

  • Paez-Ribes M, Allen E, Hudock J et al (2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15:220–231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paez-Ribes M, Man S, Xu P et al (2015) Potential proinvasive or metastatic effects of preclinical antiangiogenic therapy are prevented by concurrent chemotherapy. Clin Cancer Res 21:5488–5498

    Article  CAS  PubMed  Google Scholar 

  • Parker BS, Argani P, Cook BP et al (2004) Alterations in vascular gene expression in invasive breast carcinoma. Cancer Res 64:7857–7866

    Article  CAS  PubMed  Google Scholar 

  • Patan S, Munn LL, Jain RK (1996) Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis. Microvasc Res 51:260–272

    Article  CAS  PubMed  Google Scholar 

  • Pezzella F, Di Bacco A, Andreola S et al (1996) Angiogenesis in primary lung cancer and lung secondaries. Eur J Cancer 32:2494–2500

    Article  Google Scholar 

  • Pezzella F, Pastorino U, Tagliabue E et al (1997) Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis. Am J Pathol 151:1417–1423

    CAS  PubMed  PubMed Central  Google Scholar 

  • Raffaghello L, Vacca A, Pistoia V et al (2015) Cancer associated fibroblasts in hematological malignancies. Oncotarget 6:2589–2603

    Article  PubMed  Google Scholar 

  • Rapisarda A, Melillo G (2009) Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies. Drug Resist Updat 12:74–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ribatti D (2009) Endogenous inhibitors of angiogenesis: a historical review. Leuk Res 33:638–644

    Article  CAS  PubMed  Google Scholar 

  • Ribatti D (2012) Cancer stem cells and tumor angiogenesis. Cancer Lett 321:13–17

    Article  CAS  PubMed  Google Scholar 

  • Ribatti D (2013) Mast cells and macrophages exert beneficial and detrimental effects on tumor progression and angiogenesis. Immunol Lett 152:83–88

    Article  CAS  PubMed  Google Scholar 

  • Ribatti D, Crivellato E (2009) Immune cells and angiogenesis. J Cell Mol Med 13:2822–2833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ribatti D, Djonov V (2012) Intussusceptive microvascular growth in tumors. Cancer Lett 316:126–131

    Article  CAS  PubMed  Google Scholar 

  • Ribatti D, Vacca A, Dammacco F (1999) The role of vascular phase in solid tumor growth: a historical review. Neoplasia 1:293–302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ribatti D, Nico B, Floris C et al (2005) Microvascular density, vascular endothelial growth factor immunoreactivity in tumor cells, vessel diameter and intussusceptive microvascular growth in primary melanoma. Oncol Rep 14:81–84

    PubMed  Google Scholar 

  • Ribatti D, Nico B, Crivellato E et al (2007a) The history of the angiogenic switch concept. Leukemia 21:44–52

    Article  CAS  PubMed  Google Scholar 

  • Ribatti D, Conconi MT, Nussdorfer GG (2007b) Non-classic endogenous novel regulators of angiogenesis. Pharmacol Rev 59:185–205

    Article  CAS  PubMed  Google Scholar 

  • Ribatti D, Nico B, Crivellato E et al (2007c) The structure of the vascular networks of tumors. Cancer Lett 248:18–23

    Article  CAS  PubMed  Google Scholar 

  • Ribatti D, Nico B, Crivellato E (2011) The role of pericytes in angiogenesis. Int J Dev Biol 55:261–268

    Article  CAS  PubMed  Google Scholar 

  • Ricci-Vitiani L, Pollini R, Biffoni M et al (2010) Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 468:824–828

    Article  CAS  PubMed  Google Scholar 

  • Rigamonti N, Kadioglu E, Keklikoglou I et al (2014) Role of angiopoietin-2 in adaptive tumor resistance to VEGF signaling blockade. Cell Rep 8:696–706

    Article  CAS  PubMed  Google Scholar 

  • Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550

    Article  CAS  PubMed  Google Scholar 

  • van der Schaft DW, Hillen F et al (2005) Tumor cell plasticity in Ewing sarcoma, an alternative circulatory system stimulated by hypoxia. Cancer Res 65:11520–11528

    Article  PubMed  CAS  Google Scholar 

  • Semenza GL (2012) Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci 33:207–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Semenza GL (2014) Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu Rev Pathol 9:47–71

    Article  CAS  PubMed  Google Scholar 

  • Sennino B, Falcon BL, McCauley D et al (2007) Sequential loss of tumor vessel pericytes and endothelial cells after inhibition of platelet-derived growth factor B by selective aptamer AX102. Cancer Res 67:7358–7367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shojaei F, Wu X, Malik AK et al (2007) Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 25:911–920

    Article  CAS  PubMed  Google Scholar 

  • Shojaei F, Singh M, Thompson JD et al (2009) Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression. Proc Natl Cancer Inst 105:2640–2645

    Google Scholar 

  • Shojaei F, Simmons BH, Lee JH et al (2012) HGF/c-met pathway is one of the mediators of sunitinib-induced tumor cell type-dependent metastasis. Cancer Lett 320:48–55

    Article  CAS  PubMed  Google Scholar 

  • Sie M, Wagemakers M, Molema G et al (2009) The angiopoietin 1/angiopoietin 2 balance as a prognostic marker in primary glioblastoma multiforme. J Neurosurg 110:147–155

    Article  PubMed  Google Scholar 

  • Song S, Ewald AJ, Stallcup W et al (2005) PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 7:870–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song N, Huang Y, Shi H et al (2009) Overexpression of platelet-derived growth factor-BB increases tumor pericyte content via stromal-derived factor-1alpha/CXCR4 axis. Cancer Res 69:6057–6064

    Article  CAS  PubMed  Google Scholar 

  • St Croix B, Rago C, Velculescu V et al (2000) Genes expressed in human tumor endothelium. Science 289:1197–1202

    Article  CAS  PubMed  Google Scholar 

  • Taylor SM, Nevis KR, Park KL et al (2010) Angiogenic factor signaling regulates centrosome duplication in endothelial cells of developing blood vessels. Blood 116:3108–3117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tewari KS, Sill MW, Long HJ 3rd et al (2014) Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 370:734–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vermeuller PB, Colpaert C, Salgado R et al (2001) Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia. J Pathol 195:336–342

    Article  Google Scholar 

  • Weissleder R (2002) Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer 2:11–18

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Xiang XQ, Sun HC, Zhang W et al (2009) Human hepatocellular carcinoma tumor-derived endothelial cells manifest increased angiogenesis capability and drug resistance compared with normal endothelial cells. Clin Cancer Res 15:4838–4846

    Article  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n.278570 to DR.

Author information

Authors and Affiliations

  1. Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Policlinico - Piazza Giulio Cesare, 11, 70124, Bari, Italy

    Domenico Ribatti

  2. National Cancer Institute “Giovanni Paolo II”, Bari, Italy

    Domenico Ribatti

Authors
  1. Domenico Ribatti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Domenico Ribatti .

Editor information

Editors and Affiliations

  1. Tumor Biology Center, Freiburg, Baden-Württemberg, Germany

    Dieter Marmé

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this entry

Cite this entry

Ribatti, D. (2017). Anti-Angiogenic Cancer Therapy: Development of Resistance. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-31215-6_11-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-31215-6_11-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-31215-6

  • Online ISBN: 978-3-319-31215-6

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation