title: Elevating the Horizon: Emerging Molecular and Genomic Targets in the Treatment of Advanced Urothelial Carcinoma.
abstract: Despite recent advances in the identification of genomic alterations that lead to urothelial oncogenesis in vitro, patients with advanced urothelial carcinomas continue to have poor clinical outcomes. In the present review, we focus on targeted therapies that have yielded the most promising results alone or combined with traditional chemotherapy, including the antiangiogenesis agent bevacizumab, the human epidermal growth factor receptor 2 antibody trastuzumab, and the tyrosine kinase inhibitor cabozantinib. We also describe ongoing and developing clinical trials that use innovative approaches, including dose-dense scheduling of singular chemotherapy combinations, prospective screening of tumor tissues for mutational targets and biomarkers to predict chemosensitivity before the determination of the therapeutic regimen, and novel agents that target proteins in the immune checkpoint regulation pathway (programmed cell death protein 1 [PD-1] and anti-PD-ligand 1) that have shown significant potential in preclinical models and early clinical trials. New agents and targeted therapies, alone or combined with traditional chemotherapy, will only be validated through accrual to developing clinical trials that aim to translate these therapies into individualized treatments and improved survival rates in urothelial carcinoma.
authors: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Metin
authors: M
authors: Kurtoglu
authors: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Nicole N
authors: NN
authors: Davarpanah
authors: Health Sciences Research, Mayo Clinic, Rochester, MN.
authors: Rui
authors: R
authors: Qin
authors: Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, St. Bartholomew's Hospital, London, UK.
authors: Thomas
authors: T
authors: Powles
authors: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors: Jonathan E
authors: JE
authors: Rosenberg
authors: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. Electronic address: andrea.apolo@nih.gov.
authors: Andrea B
authors: AB
authors: Apolo
mesh_terms: D000813:Anilides / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002986:Clinical Trials as Topic; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D057285:Precision Medicine; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000627:therapeutic use; D000068878:Trastuzumab / Q000627:therapeutic use; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019459:Urothelium / Q000187:drug effects / Q000473:pathology
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011725:Pyridines; C558660:cabozantinib; D000068258:Bevacizumab; D000068878:Trastuzumab
keywords: Bladder cancer; Clinical trials; Immune checkpoints; Novel agents; Targeted therapy