Targeting Hsp90 in urothelial carcinoma
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Mahmoud Chehab1,*, Tiffany Caza2,*, Kamil Skotnicki1, Steve Landas1,2, Gennady Bratslavsky1,3, Mehdi Mollapour1,3,4, Dimitra Bourboulia1,3,4
1Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
2Department of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
3Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, USA
4Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
*These authors have contributed equally to this work
Dimitra Bourboulia, e-mail: [email protected]
Keywords: urothelial carcinoma, pathogenesis, bladder cancer treatments, heat shock protein-90, Hsp90 inhibitors
Received: November 13, 2014 Accepted: March 09, 2015 Published: March 26, 2015
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.
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