Antiangiogenic therapies: is VEGF-A inhibition alone enough?

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.