Vascular endothelial growth factor-targeted therapy in metastatic renal cell carcinoma.
Inactivation of the von Hippel-Lindau tumor suppressor gene in most sporadic renal cell carcinoma (RCC) tumors leads to a fundamental reliance on elements of this pathway, namely, the potent proangiogenic factor, vascular endothelial growth factor (VEGF). Thus, VEGF-targeted therapeutics have undergone extensive clinical testing in RCC. Approaches to bind circulating VEGF protein (eg, bevacizumab) and small molecule inhibitors of the receptor on which the VEGF ligand binds (eg, sunitinib, sorafenib, axitinib, and pazopanib) have been tested. Robust clinical effects have been observed, including high objective response rates, prolonged progression-free survival, and evidence of long overall survival for patients with metastatic RCC patients who are treated with these agents. Future directions include investigation of combination and sequenced therapy, elucidation of mechanisms of response and resistance, and exploration of the effect of these agents in other disease settings.
Rini
Brian I
BI
Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Glickman Urological and Kidney Institute, 9500 Euclid Avenue/Desk R35, Cleveland, OH 44195, USA. rinib2@ccf.org
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000077784:Axitinib; D001557:Benzenesulfonates / Q000627:therapeutic use; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007191:Indazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; C516667:pazopanib; D000077157:Sorafenib; D000077784:Axitinib; D000077210:Sunitinib