Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer

Ferrara, Napoleone; Hillan, Kenneth J.; Gerber, Hans‐Peter; Novotny, William

doi:10.1038/nrd1381

Cited by 2,279 publications

(1,577 citation statements)

References 123 publications

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“…This type of reagent would not block activation of VEGFR-2 by VEGF-C or VEGF-D, however, bispecific antibodies that bind both VEGFR-2 and VEGFR-3 (Jimenez et al, 2005) could possibly be used for this purpose. Monoclonal antibodies are well established as anticancer therapeutics, one example being an antibody to VEGF-A, known as bevacizumab or Avastin s , that is designed to restrict tumour angiogenesis and used to treat patients with metastatic colorectal cancer (Ferrara et al, 2004). …”

Section: Targeting the Vegf-c/vegf-d/vegfr-3 Signalling Axismentioning

confidence: 99%

Targeting lymphangiogenesis to prevent tumour metastasis

2006

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Recent studies involving animal models of cancer and clinicopathological analyses of human tumours suggest that the growth of lymphatic vessels (lymphangiogenesis) in or nearby tumours is associated with the metastatic spread of cancer. The best validated molecular signalling system for tumour lymphangiogenesis involves the secreted proteins vascular endothelial growth factor-C (VEGF-C) and VEGF-D that induce growth of lymphatic vessels via activation of VEGF receptor-3 (VEGFR-3) localised on the surface of lymphatic endothelial cells. In this review, we discuss the evidence supporting a role for this signalling system in the spread of cancer and potential approaches for blocking this system to prevent tumour metastasis.

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Section: Targeting the Vegf-c/vegf-d/vegfr-3 Signalling Axismentioning

confidence: 99%

Targeting lymphangiogenesis to prevent tumour metastasis

2006

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“…In February 2004, the FDA approved Bevacizumab (Avastin), a humanized anti-VEGF-A mAb, for the treatment of metastatic colorectal cancer. By ligand binding and receptor antagonism, inhibition of angiogenesis and disease progress is achieved (Kim et al, 1993;Ferrara et al, 2004). The role of Bevacizumab in other tumor types is currently under investigation, and phase III clinical trials of this drug in non-small-celllung cancer (NSCLC), renal cell cancer and metastatic breast cancer are ongoing.…”

Section: Angiogenesis Inhibition and Vascular Targetingmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

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In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents.

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“…Numerous inhibitors of the VEGF signalling axis have been developed, including the VEGF-neutralising antibody, bevacizumab, and VEGF receptor tyrosine kinase inhibitors, such as sunitinib (Ferrara et al, 2004;Ferrara and Kerbel, 2005;Ellis and Hicklin, 2008;Kerbel, 2008). These drugs are particularly effective in VEGF-driven tumours such as clear-cell renal cancer.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor 2 regulates endothelial cell sensitivity to sunitinib

et al. 2010

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The vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor sunitinib has been approved for first-line treatment of patients with metastatic renal cancer and is currently being trialled in other cancers. However, the effectiveness of this anti-angiogenic agent is limited by the presence of innate and acquired drug resistance. By screening a panel of candidate growth factors we identified fibroblast growth factor 2 (FGF2) as a potent regulator of endothelial cell sensitivity to sunitinib. We show that FGF2 supports endothelial proliferation and de novo tubule formation in the presence of sunitinib and that FGF2 can suppress sunitinib-induced retraction of tubules. Importantly, these effects of FGF2 were ablated by PD173074, a small molecule inhibitor of FGF receptor signalling. We also show that FGF2 can stimulate pro-angiogenic signalling pathways in endothelial cells despite the presence of sunitinib. Finally, analysis of clinical renal-cancer samples demonstrates that a large proportion of renal cancers strongly express FGF2. We suggest that therapeutic strategies designed to simultaneously target both VEGF and FGF2 signalling may prove more efficacious than sunitinib in renal cancer patients whose tumours express FGF2.

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Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer

Cited by 2,279 publications

References 123 publications

Targeting lymphangiogenesis to prevent tumour metastasis

Targeting lymphangiogenesis to prevent tumour metastasis

Novel antibodies as anticancer agents

Fibroblast growth factor 2 regulates endothelial cell sensitivity to sunitinib

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