title: Novel molecular targets for the therapy of urothelial carcinoma.
abstract: BACKGROUND
  First-line platinum-based combinations are active in locally advanced and metastatic urothelial carcinoma; however, long-term outcomes including disease-specific and overall survival remain suboptimal. In addition, approximately 40 - 50% of patients with advanced urothelial carcinoma have coexisting medical issues that preclude the use of cisplatin-based therapy. Improvements in our understanding of the molecular mechanisms of urothelial tumorigenesis have led to first-generation clinical trials evaluating novel agents targeting molecular pathways. These are particularly relevant in regard to subpopulations. Novel trial designs warrant consideration to accelerate accrual.
  
  
  METHODS
  In this review, novel molecular targets for the therapy of urothelial carcinoma, as well as recently completed and ongoing clinical trials utilizing novel targeted agents, are discussed. A Medline search with key words, abstracts reported at national conferences on urothelial carcinoma and NCI clinical trial identifiers was used for this review.
  
  
  CONCLUSIONS
  Improved understanding of molecular biology has identified a number of new molecular targets, but there is a seeming absence of one dominant molecular driver for urothelial cancer. An adaptive and biomarker-derived strategy may be warranted. Clinical trials utilizing targeted agents are ongoing and results are awaited.
authors.affiliation: University of Texas Medical Branch , Galveston, TX , USA.
authors.forename: Bagi R P
authors.initials: BR
authors.lastname: Jana
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.forename: Noah M
authors.initials: NM
authors.lastname: Hahn
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Milowsky
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic / Q000379:methods; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D015996:Survival Rate; D019459:Urothelium / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor