title: Vascular endothelial growth factor polymorphisms: role in response and toxicity of tyrosine kinase inhibitors.
abstract: Angiogenesis is central to the growth of normal tissues and tumors. Inhibiting this pathway has been a strategy for drug development for tumors not responsive to most agents used in chemotherapy. Notably, signaling mediated by vascular endothelial growth factor (VEGF) is a key target because aberrant signaling via this pathway is frequently associated with neoangiogenesis in tumors. The drug-discovery effort to blunt VEGF signaling has led to the approval of bevacizumab and several receptor tyrosine kinase inhibitors (TKIs) that have shown efficacy in the clinical management of breast, colorectal, lung, and kidney cancer. Understanding the genetic variability in VEGF and VEGF receptor has led to identifying genotypic variations (single nucleotide polymorphisms [SNPs]) associated with treatment outcome and toxicity. Notably, identification of SNPs in VEGF associated with angiogenesis inhibitor treatment-induced hypertension and outcome provides exciting opportunities for personalized medicine to improve outcome and reduced toxicity with these novel TKIs.
authors.affiliation: Taussig Cancer Institute - R40, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. vaziris@ccf.org
authors.forename: Susan A J
authors.initials: SA
authors.lastname: Vaziri
authors.forename: Jenny
authors.initials: J
authors.lastname: Kim
authors.forename: Mahrukh K
authors.initials: MK
authors.lastname: Ganapathi
authors.forename: Ram
authors.initials: R
authors.lastname: Ganapathi
mesh_terms: D000818:Animals; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D011110:Polymorphism, Genetic / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D042442:Vascular Endothelial Growth Factors / Q000235:genetics*
chemical_list: D047428:Protein Kinase Inhibitors; D042442:Vascular Endothelial Growth Factors; D011505:Protein-Tyrosine Kinases