Hypoxia-inducible factor HIF-1α: pharmacogenetic perspective for bevacizumab therapy individualization

Pharmacogenetics of innovative angiogenic-targeted monoclonal antibody therapy, yet in its infancy, will be crucial in treatment individualization according to the genetic profile of each patient and molecular features of tumors. Bevacizumab (Avastin) specifically targets the key promotor of angiogenesis - vascular endothelial growth factor (VEGF), whose transcription is critically regulated by hypoxia-inducible factor HIF-1 alpha. The present paper points out the clinical relevance of HIF-1 alpha common genetic polymorphisms to the inter-individual variability in response to anti-VEGF-targeted monoclonal antibody therapeutic regimens, with special reference to colorectal cancer.