“Purpose of review
To present the recent advances in novel agents that target heat shock proteins ( Hsps) to treat or delay the development of castration resistant prostate cancer (CRPC).
Multiple preclinical studies have shown that silencing Hsp27, Hsp90, or clusterin sensitizes
prostate cancer cells to modern chemotherapy and radiation treatments; and overexpression of these chaperones confers resistance to these therapies. Antisense oligonucleotides targeting Hsp27 and clusterin have shown good biological activity in human phase II trials and phase III studies are ongoing. Despite promising preclinical efficacy, a number of phase I/II human trials with various Hsp90 inhibitors have been disappointing check details with negligible anticancer activity and dose-limiting toxicity profiles. Newer Hsp90 inhibitors with better toxicity profiles, and inhibitors that target Hsp90 cofactors, such as FKBP52, are currently being investigated in human studies.
Many Hsp chaperone client proteins are key components of alternative growth factor pathways upregulated in CRPC and are involved in key resistance pathways to current chemotherapy and radiotherapy regimes. New treatments that inhibit Hsps are attractive anticancer strategies as
they have the ability to simultaneously target multiple pathways involved in CRPC.”
“OBJECTIVE: Colposcopy has been used to detect epithelial damage with vaginal microbicides. In animal models, optical ATM signaling pathway coherence tomography provided increased sensitivity over colposcopy in detecting epithelial injury. This randomized, double-blinded,
clinical study compared optical coherence tomography to colposcopy for the evaluation of epithelial injury in women using placebo or nonoxynol-9.
METHODS: Thirty women aged 18-45 were randomized https://www.selleckchem.com/products/srt2104-gsk2245840.html to use hydroxyethyl cellulose placebo or nonoxynol-9 vaginal gel twice daily for 5.5 days. Imaging with colposcopy and optical coherence tomography was performed before product use, after the last dose, and 1 week later. Colposcopy was graded using standard criteria. Optical coherence tomography images were scored for epithelial integrity based on a published scoring system and were measured for epithelial thickness.
RESULTS: Colposcopy findings, optical coherence tomography scores, and epithelial thicknesses were similar between treatment groups at baseline. After treatment, there were significant differences between the nonoxynol-9 (1.37) and control group (1.15) optical coherence tomography scores (P<.001), indicating epithelial injury, and there was epithelial thinning in the nonoxynol-9 group (237 micrometers) compared with the control group (292 micrometers; P=.008). There were no significant posttreatment colposcopic differences in epithelial disruption between treatment groups, with only increased erythema noted after nonoxynol-9 use (P=.02).
CONCLUSION: Optical coherence tomography detected epithelial disruption and thinning not identified by colposcopy.