title: Targeting Hsp90 in urothelial carcinoma.
abstract: Urothelial carcinoma, or transitional cell carcinoma, is the most common urologic malignancy that carries significant morbidity, mortality, recurrence risk and associated health care costs. Despite use of current chemotherapies and immunotherapies, long-term remission in patients with muscle-invasive or metastatic disease remains low, and disease recurrence is common. The molecular chaperone Heat Shock Protein-90 (Hsp90) may offer an ideal treatment target, as it is a critical signaling hub in urothelial carcinoma pathogenesis and potentiates chemoradiation. Preclinical testing with Hsp90 inhibitors has demonstrated reduced proliferation, enhanced apoptosis and synergism with chemotherapies and radiation. Despite promising preclinical data, clinical trials utilizing Hsp90 inhibitors for other malignancies had modest efficacy. Therefore, we propose that Hsp90 inhibition would best serve as an adjuvant treatment in advanced muscle-invasive or metastatic bladder cancers to potentiate other therapies. An overview of bladder cancer biology, current treatments, molecular targeted therapies, and the role for Hsp90 inhibitors in the treatment of urothelial carcinoma is the focus of this review.
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Chehab
authors.affiliation: Department of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Caza
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Kamil
authors.initials: K
authors.lastname: Skotnicki
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.|Department of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Landas
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.|Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Gennady
authors.initials: G
authors.lastname: Bratslavsky
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.|Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, USA.|Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mollapour
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.|Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, USA.|Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Bourboulia
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D001500:BCG Vaccine / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D015653:Cystectomy; D019008:Drug Resistance, Neoplasm; D015507:Drugs, Investigational / Q000627:therapeutic use; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D042421:Histone Code / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009130:Muscle, Smooth / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014571:Urologic Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001500:BCG Vaccine; D015507:Drugs, Investigational; D018841:HSP90 Heat-Shock Proteins; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors
keywords: Hsp90 inhibitors; bladder cancer treatments; heat shock protein-90; pathogenesis; urothelial carcinoma