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 155
- Downloads 0
Secondary Vesical Calculi Formation on Non Absorbable Sutures Following Abdominal Hysterectomy: A Case Report
We report an uncommon case of a-48-year-old female presenting with calculi over suture in bladder following prior abdominal hysterectomy. The stone was fragmented and removed via transurethral cystolitholapaxy using pneu...
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...
Longest Survival with Renal AA Amyloidosis: Development of End Stage Renal Disease after 25 Years of AA Amyloidosis Diagnosis
This is case report of a patient who was diagnosed with secondary AA Amyloidosis of the kidneys due to Pulmonary Tuberculosis in 1973. AA Amyloidosis was diagnosed based on renal biopsy due to heavy proteinuria. Nephroti...
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...
Handgrip Strength and Weight Predict Long-Term Mortality in Acute Kidney Injury Patients
Introduction: Surviving acute kidney (AKI) patients have a higher late mortality. The negative impact of malnutrition on the early outcome of AKI patients has recently been confirmed by various studies. However, its impa...