title: Targeted therapeutic strategies for the management of renal cell carcinoma.
abstract: OBJECTIVE
  This article reviews recent developments in the use of systemic targeted therapies for the treatment of advanced clear and nonclear cell renal cell carcinoma (RCC). The genetic/molecular basis of each form of RCC is discussed and current treatments and clinical trials are described.
  
  
  RESULTS
  The treatment of advanced RCC continues to be a major challenge for uro-oncologists. The rapid growth in therapeutic options has brought much needed improvements in overall and progression-free survival, although durable complete responses remain elusive. The recent identification of mutations in genes involved in chromatin remodeling will likely lead to the investigation of whether components of this critical process can also be valid therapeutic targets in clear cell RCC. Similarly, efforts to decipher the molecular mechanisms underlying nonclear cell variants of RCC are beginning to engender novel therapeutic strategies directed against these rarer forms of kidney cancer. Despite the availability of multiple treatment options, several challenges remain: selecting the best first-line or subsequent therapy for a given patient, the optimal sequencing of the various agents available, designing trials with appropriate comparison arms and endpoints, and identifying well tolerated and effective drug combinations.
  
  
  CONCLUSIONS
  Agents targeting the vascular endothelial growth factor and mammalian target of rapamycin pathways remain the mainstay in the management of metastatic RCC. Ongoing and future studies are expected to facilitate the development of therapeutic regimens that incorporate agents with improved tolerability and enhanced efficacy by continuing to capitalize on the strides made by basic and translational scientists in uncovering the mechanisms underlying the various forms of RCC.
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Singer
authors.forename: Gopal N
authors.initials: GN
authors.lastname: Gupta
authors.forename: Ramaprasad
authors.initials: R
authors.lastname: Srinivasan
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007191:Indazoles; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D014402:Tuberous Sclerosis / Q000188:drug therapy; D014481:United States / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007191:Indazoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011743:Pyrimidines; D013449:Sulfonamides; D009536:Niacinamide; C516667:pazopanib; D000077157:Sorafenib