Vascular endothelial growth factor-targeted therapy in renal cell carcinoma: current status and future directions.
Renal cell carcinoma is a highly vascular tumor associated with expression of vascular endothelial growth factor (VEGF). Recently, VEGF-targeted therapies have been identified as a promising therapeutic approach. Three agents targeting the VEGF pathway have shown clinical activity as monotherapy in metastatic renal cell carcinoma: the anti-VEGF monoclonal antibody, bevacizumab, and small-molecule VEGF receptor tyrosine kinase inhibitors, sorafenib and sunitinib. This article explores these agents in terms of their mechanisms of action, clinical efficacy, and toxicity profiles. This article also reviews future development strategies, including combination regimens and drug sequencing, trial design considerations, and patient selection opportunities.
Rini
Brian I
BI
Department of Solid Tumor Oncology and Urology, Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, USA. rinib2@ccf.org
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000494:pharmacology; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D002986:Clinical Trials as Topic; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology; D011758:Pyrroles / Q000009:adverse effects / Q000494:pharmacology; D000077157:Sorafenib; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D000077210:Sunitinib