Determining the source of regenerated luminal epithelial cells in the adult prostate during androgen deprivation and replacement will provide insights into the origin of prostate cancer cells and their fate during androgen deprivation therapy. Prostate stem cells in the epithelial layer have been suggested to give rise to luminal epithelium. However, the extent of stem cell participation to prostate regrowth is not clear. In this report, using prostate-specific antigen-CreER(T2)-based genetic lineage marking/tracing in mice, preexisting luminal epithelial cells were shown to be a source of regenerated luminal epithelial cells in the adult prostate. Prostatic luminal epithelial cells could survive androgen deprivation and were capable of proliferating upon androgen replacement. Prostate cancer cells, typically exhibiting a luminal epithelial phenotype, may retain this intrinsic capability to survive and regenerate in response to changes in androgen signaling, providing part of the mechanism for the ultimate failure of androgen deprivation therapy in prostate cancer.

Acute kidney injury after partial nephrectomy was not a significant or independent predictor of long-term functional decline in our institutional cohort. A prospective study with larger sample sizes and longer followup is required to evaluate factors associated with long-term nephron stability.

Historically, androgen-deprivation therapy has been the cornerstone for treatment of metastatic prostate cancer. Unfortunately, nearly majority patients with prostate cancer transition to the refractory state of castration-resistant prostate cancer (CRPC). Newer therapeutic agents are needed for treating these CRPC patients that are unresponsive to androgen deprivation and/or chemotherapy. The histone deacetylase (HDAC) family of enzymes limits the expression of genomic regions by improving binding between histones and the DNA backbone. Modulating the role of HDAC enzymes can alter the cell's regulation of proto-oncogenes and tumor suppressor genes, thereby regulating potential neoplastic proliferation. As a result, histone deacetylase inhibitors (HDACi) are now being evaluated for CRPC or chemotherapy-resistant prostate cancer due to their effects on the expression of the androgen receptor gene. In this paper, we review the molecular mechanism and functional target molecules of different HDACi as applicable to CRPC as well as describe recent and current clinical trials involving HDACi in prostate cancer. To date, four HDAC classes comprising 18 isoenzymes have been identified. Recent clinical trials of vorinostat, romidepsin, and panobinostat have provided cautious optimism towards improved outcomes using these novel therapeutic agents for CPRC patients. Nevertheless, no phase III trial has been conducted to cement one of these drugs as an adjunct to androgen-deprivation therapy. Consequently, further investigation is necessary to delineate the benefits and drawbacks of these medications.

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Patients earlier in their disease course with <5 BSI, low pain score, and good ECOG performance status are optimal candidates for radium-223. Radium-223 therapy is well tolerated with most patients reporting declines in pain scores and BSI. Prostate 77:479-488, 2017. © 2016 Wiley Periodicals, Inc.