title: Current and future strategies in nonclear-cell metastatic renal cell carcinoma.
abstract: OBJECTIVE
  Therapeutic options for patients with metastatic nonclear-cell renal cell carcinoma (non-ccRCC) are limited and display minimum benefit. Conducting clinical trials in these rare and heterogeneous diseases without identified key biological drivers is a challenge for drug development. A growing body of prospective dedicated clinical trials and large molecular characterization initiatives are raising new expectations in non-ccRCC.
  
  
  RESULTS
  The first randomized phase II study in non-ccRCC failed to demonstrate the benefit of everolimus over sunitinib in first-line setting, although this study was small and was not supposed to draw final conclusions. Single-arm phase II trials have reported the results of sunitinib or everolimus in the papillary. The potential role of a sunitinib-gemcitabine combination has been investigated in RCC with sarcomatoid features. In parallel, the molecular characterization of non-ccRCC has been initiated, highlighting the heterogeneity of the distinct subtypes.
  
  
  CONCLUSIONS
  Current efforts to develop clinical trials in non-ccRCC have provided preliminary results with approved agents. The molecular characterization programs have not yet translated into clinical meaningful results, but MET proto-oncogene inhibition holds promises in the population of papillary RCC. Non-ccRCC management raises the challenge of structuring networks to optimize pathological diagnosis, target identification, and for dedicated clinical trials design.
authors.affiliation: Genitourinary Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D025202:Molecular Diagnostic Techniques; D058990:Molecular Targeted Therapy; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas