Antiangiogenic therapies: is VEGF-A inhibition alone enough?

Abstract

Although available targeted therapies provide some clinical efficacy, a need remains for antiangiogenic therapies with alternative mechanisms in order to provide better outcomes and the ability to circumvent resistance. Inhibition of multiple VEGF targets may produce enhanced efficacy and more durable responses through synergistic effects, and prevent the development of escape mechanisms. Inhibition of VEGF-A, VEGF-C and VEGF-D with broad-spectrum VEGF receptor-2 (VEGFR-2) inhibitors, such as the novel protein therapeutic CT-322, may result in increased efficacy and prevent or delay acquired resistance and metastatic spread often seen with VEGF-A inhibition alone. Therefore, panoramic inhibition of VEGFR-2 may be a better approach to more effective antiangiogenic therapy. This article focuses on pivotal data on VEGF/VEGFR inhibitors currently in use, as well as newer agents in development.

Keywords::

• adnectin
• antiangiogenesis
• CT-322
• VEGF-A
• VEGFR inhibitors

Financial & competing interests disclosure

Michael S Gordon receives research support from Genentech, Exelixis and Pfizer for the performance of clinical trials. Michael S Gordon also serves as a consultant for Genentech and Pfizer. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Editorial support was provided by U Lena Prisco of PAREXEL and was funded by Bristol-Myers Squibb.