title: Fibroblast growth factor receptors as therapeutic targets in clear-cell renal cell carcinoma.
abstract: BACKGROUND
  Metastatic clear-cell renal cell carcinoma (RCC) is a highly vascularized tumor type that is often associated with inactivating mutations in the von Hippel-Lindau gene that ultimately drives pro-angiogenic signaling pathways, including the VEGF pathway. As such, new therapies indicated for RCC have largely focused on blocking angiogenesis by inhibiting this pathway. Despite the contribution of these agents to clinical outcomes in RCC, acquired resistance that stimulates tumor regrowth and revascularization quickly emerges. Resistance to VEGF inhibition appears to largely result from activation of compensatory angiogenesis pathways (including the fibroblast growth factor [FGF] pathway), providing a rationale to investigate their inhibition.
  
  
  METHODS
  This review explores the role of the FGF pathway in resistance to VEGF-targeted therapy and rationale for targeting in RCC. PubMed, as well as ASCO and ESMO congress abstracts, were searched for preclinical and clinical data for FGF inhibitors in RCC.
  
  
  CONCLUSIONS
  The FGF pathway presents a logical target in RCC and trials of the FGF receptor inhibitors regorafenib, dovitinib, nintedanib, lenvatinib and cediranib demonstrated clinical activity. Clinical development should focus on optimizing the use of this therapy by improving patient selection and evaluating combined therapy.
authors.affiliation: University of Alabama at Birmingham Comprehensive Cancer Center, Division of Hematology and Oncology , 1720 2nd Avenue South, WTI 5, Birmingham, AL 35294-3300 , USA +1 205 975 3742 ; +1 205 934 9511 ; gsonpavde@uabmc.edu.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Willey
authors.forename: Sunil
authors.initials: S
authors.lastname: Sudarshan
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors