Efficacy of the Hsp90 Inhibitors in Prostate Cancer Therapy
Journal Title: Journal of Urology & Nephrology - Year 2014, Vol 1, Issue 1
Abstract
Prostate cancer is a disease of aging and the second leading cause of death in men in the United States. A distinctive characteristic of prostate tumors is their dependence on androgen for development, growth and survival. The molecular chaperone Heat Shock Protein-90 (Hsp90) is involved in the stability of a number of protein targets including androgen receptor (AR). Preclinical data demonstrates Hsp90 inhibition to be an effective therapy for inhibiting prostate cancer cells in culture as well as in animal xenograft models. Two newgeneration Hsp90 inhibitors, ganetespib and AT13387, are currently being evaluated as single or combinational therapies in the clinic for castrate resistant prostate cancer (CRPC). While clinical signs of antitumor activity have been observed with new-generation HSP90 inhibitors, these drugs are likely to be most effective when used as part of combination treatments. This review highlights how inhibition of Hsp90 combined with specific secondary targets including Wee1, Hsp27, ERK and mTOR displays enhanced inhibitory effects in pre-clinical models. One clinical benefit of co-inhibition is the targeting of multiple signaling pathways. In addition, the variety of proposed combination therapies allows for latitude in selecting a secondary target, potentially tailoring therapies to specific patient populations.
Authors and Affiliations
Mehdi Mollapour
Keywords
Related Articles
- EP ID EP207434
- DOI 10.13188/2380-0585
- Views 138
- Downloads 0
Bacterial Ecology of Peritonitis in a Sub-Saharan Peritoneal Dialysis Unit
Introduction: Peritonitis is a common and serious complication of Peritoneal Dialysis (PD). Peritonitis is a major cause of PD technique failure and conversion to long-term hemodialysis. After acquiring 10 years of exper...
Utility of Fluorescent In Situ Hybridization in Addition to Voided Urine Cytology in The Diagnostic Work Up of Bladder Cancer Patients: A Pilot Study from A South Indian Referral Laboratory
Background: Bladder cancer (BC) is amongst the most prevalent cancers associated with urinary tract. Although voided urine cytology (VUC) is currently an important urine-based laboratory test, it falls short due to high...
Incidence and Risk Factors for Hemorrhagic Complications after Percutaneous Renal Biopsy using a 16-Gauge Needle Followed by 6 Hours of Bed Rest
Background: The procedures and management protocols forpercutaneous renal biopsy (PRB) are different among institutions. Herewe present the outcomes of our protocol and identify risk factors forhemorrhagic complications...
Bid Cleavage and TRAIL Sensitivity in Urothelial Cell Carcinoma of the Bladder
opensity to recur after resection. Intravesical bacillus calmetteguerin (BCG) therapy significantly reduces recurrence of UCCB, and response to BCG therapy is believed to be mediated by tumor necrosis factor related apop...
Early Surgical Correction of Ureteropelvic Junction Obstruction
Based on the analysis of 131 (from month 1 to 3 years old) children with Ureteropelvic Junction (UPJ) obstruction, who underwent early pyeloplasty, it was found that the incidence of intra and postoperative complications...