Aflibercept: A Novel VEGF Targeted Agent to Explore the Future Perspectives of Anti-Angiogenic Therapy for the Treatment of Multiple Tumors

Tina      Sharma; Richa      Dhingra; Sukhminder      Singh; Shivani      Sharma; Prince      Tomar; Manav      Malhotra; T.      R. Bhardwaj

Abstract

Angiogenesis is the process of formation of new blood vessels due to over expression of VEGF (vascular endothelial growth factor) which plays a critical role in the growth and development of all solid tumor types. With the advancement in understanding of tumor angiogenesis and VEGF, there have been a number of agents developed to target VEGF for the treatment of cancer. These targeted agents can affect downstream VEGF signal transduction by unique mechanisms at different cellular and extracellular levels. FDA has recently approved Aflibercept or VEGF-Trap in August 2012 for the treatment of colorectal cancer. It is a recombinant, decoy receptor fusion protein, rationally designed to block angiogenesis by targeting VEGF-A, VEGF-B and placental growth factor. VEGF-Trap exerts its antiangiogenic effects through regression of tumor vasculature, remodelling or normalization of surviving vasculature and inhibition of new tumor vessel growth. In this review, pre-clinical and clinical data have been summarized for aflibercept alone and in combination with chemotherapy to explore its efficacy and benefits in ovarian cancer, breast cancer, non-small cell lung cancer, pancreatic cancer, glioblastoma, adenocarcinoma and renal cell cancer xenograft models.

Keywords: Aflibercept, angiogenesis, chemotherapy, VEGF, VEGF-Trap, endothelial, bevacizumab, PHARMACODYNAMICS