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Review: monoclonal antibodies to the vascular endothelial growth factor receptor-2 in cancer therapy
Hagop Youssoufian1, Daniel J Hicklin, Eric K Rowinsky
1Clinical Affairs Department, ImClone Systems, Inc., Branchburg, New Jersey 08876, USA. hagop.youssoufian@imclone.com
Abstract:
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.
Insights
Angiogenesis drives cancer growth. Targeting vascular endothelial growth factor receptor-2 (VEGFR-2) with inhibitors or antibodies shows promise for cancer therapy, with approved drugs already available.
Area of Science:
- Oncology
- Molecular Biology
- Drug Development
Background:
- Angiogenesis is crucial for tumor growth and metastasis.
- Current cancer therapies include small-molecule inhibitors and antibodies targeting angiogenesis.
- Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) is a key regulator of angiogenesis.
Purpose of the Study:
- To discuss the role of VEGFR-2 in cancer.
- To review ongoing efforts in developing VEGFR-2-specific monoclonal antibodies for cancer treatment.
Main Methods:
- Review of existing literature on angiogenesis inhibitors.
- Analysis of the mechanism of action for small-molecule VEGFR-2 inhibitors.
- Discussion of antibody-based therapeutic strategies targeting VEGFR-2.
Main Results:
- VEGFR-2 is a validated target in cancer therapy.
- Small-molecule inhibitors targeting VEGFR-2 are approved for renal cell cancer and gastrointestinal stromal tumors.
- Monoclonal antibodies offer potential for enhanced potency and tolerability in VEGFR-2 targeted therapy.
Conclusions:
- VEGFR-2 remains a significant target for anti-cancer drug development.
- Development of specific monoclonal antibodies against VEGFR-2 is a promising therapeutic strategy.
- Targeting VEGFR-2 contributes to controlling cancer progression and invasion.
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