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  • Review Article
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Targeting angiogenesis: progress with anti-VEGF treatment with large molecules

Nature Reviews Clinical Oncology volume 6, pages 507–518 (2009)Cite this article

Abstract

Angiogenesis—one of the hallmarks of cancer—has emerged as a valid therapeutic target in oncology. The VEGF system represents a key mediator of tumor-initiated angiogenesis and the first target of antiangiogenesis agents introduced in clinical practice. Although anti-VEGF therapies have clearly demonstrated antitumor efficacy in various malignancies, especially when combined with conventional cytotoxic chemotherapy, their mechanism of action is not fully understood. This Review will discuss the rationale for using antiangiogenic compounds and will focus on large molecules, such as antibodies, that target the VEGF system. Clinical data on bevacizumab is discussed in detail. Predictive markers for anti-VEGF agents have not yet been identified and questions regarding the usefulness of bevacizumab in the adjuvant setting as well as its continued use beyond progression remain unanswered, in spite of negative data on bevacizumab in treating patients with adjuvant colon cancer. Nonetheless, anti-VEGF therapy has enhanced the arsenal of anticancer therapies and has provided new insights into the biology of malignancy.

Key Points

  • Anti-VEGF therapy with bevacizumab can increase overall survival and/or progression-free survival in patients with colorectal, breast, lung cancer or glioblastoma multiforme when combined with cytotoxic agents

  • In spite of its well-documented efficacy in advanced malignancies, bevacizumab has not yet shown to be active as adjuvant therapy

  • Anti-VEGF therapy is thought to transiently 'normalize' the tumor vasculature and improve the delivery of drugs and oxygen to tumor cells, rendering them more chemosensitive and radiosensitive

  • No predictive biomarker for the efficacy of anti-VEGF therapy has been identified, which would allow the selection of patients who may obtain maximum benefit from anti-VEGF treatment

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Figure 1: VEGF receptors and their specific ligands.

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  1. Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA

    Axel Grothey & Evanthia Galanis

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Correspondence to Axel Grothey.

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A. Grothey declares he is a consultant for Amgen, Genentech and Pfizer. He also receives grant/research support from Bayer and Genentech. E. Galanis declares she receives grant/research support from Bayer and Genentech.

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Grothey, A., Galanis, E. Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nat Rev Clin Oncol 6, 507–518 (2009). https://doi.org/10.1038/nrclinonc.2009.110

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