title: Beyond conventional chemotherapy: Emerging molecular targeted and immunotherapy strategies in urothelial carcinoma.
abstract: Advanced urothelial carcinoma is frequently lethal, and improvements in cytotoxic chemotherapy have plateaued. Recent technological advances allows for a comprehensive analysis of genomic alterations in a timely manner. The Cancer Genome Atlas (TCGA) study revealed that there are numerous genomic aberrations in muscle-invasive urothelial carcinoma, such as TP53, ARID1A, PIK3CA, ERCC2, FGFR3, and HER2. Molecular targeted therapies against similar genetic alterations are currently available for other malignancies, but their efficacy in urothelial carcinoma has not been established. This review describes the genomic landscape of malignant urothelial carcinomas, with an emphasis on the potential to prosecute these tumours by deploying novel targeted agents and immunotherapy in appropriately selected patient populations.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, and Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, La Jolla, CA, USA. Electronic address: saikeda@ucsd.edu.
authors.forename: Sadakatsu
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Pathology, Division of Anatomic Pathology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hansel
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, and Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D019468:Disease Management; D056466:Histone Demethylases / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D035703:Therapies, Investigational; D014157:Transcription Factors / Q000235:genetics; D014571:Urologic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D056466:Histone Demethylases; C523998:KDM6A protein, human
keywords: Genetic aberrations; Immune therapy; Targeted therapy; Urothelial carcinoma