title: Targeting Signaling Transduction Pathways in Bladder Cancer.
abstract: Systemic therapy for urothelial carcinoma (UC) of the bladder has largely revolved around cytotoxic chemotherapy regimens. However, several recent clinical trials have explored the roles of targeted therapies which specifically inhibit signal transduction pathways. Simultaneously, a rationale for such therapies has come to the forefront of management of this disease because an overabundance of signaling pathways are genetically deranged as a result of point mutation or copy number alteration (CNA) as identified by several recent next generation sequencing (NGS) studies. Importantly, these derangements are found in all stages of disease, and therefore targeted therapies hold promise as a next step in the evolution of the medical management of both localized and metastatic UCC. We review the rationale for and progress in studying inhibition of signal transduction as a means of treatment of UCC.
authors.affiliation: Department of Surgical Oncology, Division of Urologic Oncology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA. philip.abbosh@fccc.edu.
authors.forename: Phillip H
authors.initials: PH
authors.lastname: Abbosh
authors.affiliation: Departments of Urology and Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. dmcconke@mdanderson.org.|The University of Texas-Graduate School of Biomedical Sciences (GSBS) at Houston, Houston, TX, 77030, USA. dmcconke@mdanderson.org.
authors.forename: David J
authors.initials: DJ
authors.lastname: McConkey
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA. elizabeth.plimack@fccc.edu.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Plimack
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000235:genetics; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Bevacizumab; Bladder cancer; Cetuximab; Chemotherapy; Copy number abnormality; Dovitinib; EGFR; ERBB2; ERBB3; Erlotinib; Everolimus; FGFR3; Mutation; PIK3CA; PTEN; Pazopanib; Sunitinib; mTOR