title: Targeted therapies in urothelial carcinoma.
abstract: OBJECTIVE
  Greater understanding of the biology and genetics of urothelial carcinoma is helping to identify and define the role of molecules and pathways appropriate for novel-targeted therapies. Here, we review the targeted therapies that have been reported or are in ongoing urothelial carcinoma clinical trials, and highlight molecular targets characterized in preclinical and clinical studies.
  
  
  RESULTS
  Trials in nonmuscle-invasive bladder cancer are evaluating the role of immunotherapy and agents targeting vascular endothelial growth factor (VEGF) or fibroblast growth factor receptor-3. In muscle-invasive bladder cancer, neoadjuvant studies have focused on combining VEGF agents with chemotherapy; adjuvant studies are testing vaccines and agents targeting the human epidermal growth factor receptor 2, p53, and Hsp27. In the first-line treatment of metastatic urothelial carcinoma, tubulin, cytotoxic T-lymphocyte antigen 4, Hsp27, and p53 are novel targets in clinical trials. The majority of targeted agents studied in urothelial carcinoma are in the second-line setting; new targets include CD105, polo-like kinase-1, phosphatidylinositide 3-kinases (PI3K), transforming growth factor β receptor/activin receptor-like kinase β, estrogen receptor, and the hepatocyte growth factor receptor (HGFR or MET).
  
  
  CONCLUSIONS
  Development of targeted therapies for urothelial carcinoma is still in early stages, consequently there have been no major therapeutic advances to date. However, greater understanding of urothelial carcinoma and solid tumor biology has resulted in a proliferation of clinical trials that could lead to significant advances in treatment strategies.
authors.affiliation: aGenitourinary Malignancies Branch bUrologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Monalisa
authors.initials: M
authors.lastname: Ghosh
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Brancato
authors.forename: Piyush K
authors.initials: PK
authors.lastname: Agarwal
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Apolo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents