title: Targeting angiogenesis in renal cell carcinoma.
abstract: BACKGROUND
  Understanding the molecular pathogenesis of renal cell carcinomas (RCC) has identified targets for therapeutic intervention. The recognition of the importance of hypoxia-inducible factor-1α (HIF-1α) signaling in the pathogenesis of clear-cell RCC has led to widespread study of angiogenesis inhibitors. While the major component of the angiogenic process in RCC is VEGF, targeting of the mTOR pathway is important because activation of the upstream PI3K/Akt/mTOR signaling pathways is one method by which constitutive HIF-1α activation or upregulation occurs.
  
  
  METHODS
  Current FDA-approved anti-angiogenic agents as first- and second-line treatment for RCC, as well as agents in development will be reviewed.
  
  
  CONCLUSIONS
  Novel agents targeting non-VEGFR signals in kidney cancer will be met with new successes and new challenges in therapeutic development. While several of these agents will likely show activity, they may accentuate toxicity. Careful triage of these agents paired with biomarker studies will facilitate development of these agents and identification of those patients most likely to benefit from these emerging therapies.
authors.affiliation: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Urologic Oncology Program , 8700 Beverly Blvd, Los Angeles, CA 90048 , USA +1 310 423 7600 ; +1 310 659 3928 ; Edwin.Posadas@cmc.edu.
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Posadas
authors.forename: Suwicha
authors.initials: S
authors.lastname: Limvorasak
authors.forename: Shaleekha
authors.initials: S
authors.lastname: Sharma
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D005346:Fibroblast Growth Factors; C546842:MTOR protein, human; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases