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Review: Monoclonal Antibodies to the Vascular Endothelial Growth Factor Receptor-2 in Cancer Therapy

Authors' Affiliation: Clinical Affairs Department, ImClone Systems, Inc., Branchburg, New Jersey

Requests for reprints: Hagop Youssoufian, ImClone Systems, Inc., 33 ImClone Drive, Branchburg, NJ 08876. Phone: 908-541-8287; Fax: 908-231-9885; E-mail: hagop.youssoufian{at}imclone.com.

Angiogenesis is a fundamental mechanism of cancer growth and invasion. Current translational approaches are using both small-molecule inhibitors and antibodies that modulate various steps of these processes, and several such compounds have already received regulatory approval for the therapy of specific indications in cancer. Among the many molecular targets involved in the control of angiogenesis, the vascular endothelial growth factor receptor-2 (VEGFR-2; or kinase insert domain-containing receptor) is attractive as shown in part by the efficacy of small-molecule inhibitors directed to this receptor. Two small-molecule inhibitors that target VEGFR-2 have recently been granted approval for the treatment of renal cell cancer and gastrointestinal stromal tumors. The development of antibodies that can selectively block VEGFR-2 could potentially result in improved potency or tolerability. Here, we discuss the role of VEGFR-2 in cancer and ongoing efforts to develop highly specific monoclonal antibodies for cancer therapy.