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  • Review Article
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Drug Insight: VEGF as a therapeutic target for breast cancer

Nature Clinical Practice Oncology volume 4, pages 181–189 (2007)Cite this article

Abstract

Angiogenesis is implicated in the pathogenesis of malignancy and metastasis. Inhibition of angiogenesis has demonstrated clinically significant improvements in outcomes in a variety of malignancies, including breast cancer. The humanized monoclonal antibody against VEGF, bevacizumab, is the clinically most mature of the antiangiogenic agents and has recently been shown to improve outcome when combined with chemotherapy in the first-line metastatic setting of breast cancer. A variety of other antiangiogenic agents are currently under investigation, including drugs that inhibit the VEGF receptor 2, the cognate receptor for VEGF found on endothelial cells. The combination of antiangiogenic drugs with one another and with other biologic agents is also being explored in an attempt to improve efficacy and to overcome the drug resistance seen with the initial studies of antiangiogenic agents. This Review will focus on the current state of therapeutics designed to inhibit this angiogenic process in breast cancer.

Key Points

  • Antiangiogenic therapy has demonstrated antitumor efficacy in multiple tumor types, including breast cancer

  • Multiple agents are currently being studied that target various aspects of the VEGF pathway, including VEGF, the external domain of the VEGF receptor, and the intracellular tyrosine kinase domain of the VEGF receptor

  • According to the results of a phase III trial in patients with untreated metastatic breast cancer, bevacizumab increases both objective response rates and median progression-free survival when combined with standard chemotherapy versus chemotherapy alone

  • There is an urgent need to identify biomarkers to guide antiangiogenic therapy in order to establish the optimum dose and to determine which patients might benefit most from a given drug

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Figure 1: Schematic representation of antiangiogenesis agents that target the VEGF receptor and its signaling pathway

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Authors and Affiliations

  1. BP Schneider is Assistant Professor of Medicine at Indiana University with joint appointment to the divisions of Hematology/Oncology and Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA. GW Sledge, Jr is the Ballve-Lantero Professor of Oncology at Indiana University School of Medicine, Indianapolis, and is the Chair of the Breast Committee of the Eastern Cooperative Oncology Group.,

    Bryan P Schneider & George W Sledge Jr

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Correspondence to George W Sledge Jr.

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Competing interests

GW Sledge declared he is a paid consultant for Genentech Oncology (the manufacturers of bevacizumab) and for Pfizer (the manufacturers of sunitinib). BP Schneider declared he has no competing interests.

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Schneider, B., Sledge, G. Drug Insight: VEGF as a therapeutic target for breast cancer. Nat Rev Clin Oncol 4, 181–189 (2007). https://doi.org/10.1038/ncponc0740

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