LABORATORY RESEARCH Resistance to Docetaxel in Prostate Cancer Is Associated with Androgen Receptor Activation and Loss of KDM5D Expression Investigators demonstrated that the prostate cancer cell lines LNCaP and LAPC4 display markedly different sensitivity to docetaxel with androgen receptor activation, and RNA-seq analysis of these cell lines identified KDM5D (lysine-specific demethylase 5D) encoded on the Y chromosome as a potential mediator of this sensitivity. [Proc Natl Acad Sci USA] Abstract ERG Signaling in Prostate Cancer Is Driven through PRMT5-Dependent Methylation of the Androgen Receptor From a screen for functionally relevant ERG interactors, the authors identified the arginine methyltransferase PRMT5. ERG recruits PRMT5 to androgen receptor (AR)-target genes, where PRMT5 methylates AR on arginine 761. [Elife] Full Article p27T187A Knockin Identifies Skp2/Cks1 Pocket Inhibitors for Advanced Prostate Cancer Scientists identified pRb and p53 doubly deficient (DKO) prostate tumorigenesis as a context in which p27 ubiquitination by SCFSkp2/Cks1 is required for p27 downregulation. p27 protein accumulated in prostate when p27T187A KI mice underwent DKO prostate tumorigenesis. [Oncogene] Abstract The Marrow Niche Controls the Cancer Stem Cell Phenotype of Disseminated Prostate Cancer Researchers showed that disseminated tumor cells (DTCs) recovered from marrow were significantly enriched for a cancer stem cells (CSCs) phenotype. Critically, the conversion of DTCs to CSCs is regulated by niche-derived GAS6 through the Mer/mTOR; molecules previously shown to regulate dormancy. [Oncotarget] Full Article The Effect of F877L and T878A Mutations on Androgen Receptor Response to Enzalutamide Researchers studied the effects of enzalutamide (Enza) on F877L and T878A mutants, as well as the double mutant androgen receptor (AR) (F877L/T878A). Molecular modeling revealed favorable structural changes in the double mutant AR that lead to a decrease in steric clashes for Enza. [Mol Cancer Ther] Abstract Local Anesthetic Bupivacaine Induced Ovarian and Prostate Cancer Apoptotic Cell Death and Underlying Mechanisms In Vitro Researchers investigated the effects of bupivacaine on ovarian and prostate cancer cell biology and the underlying molecular mechanisms. [Sci Rep] Full Article Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies Only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. Scientists have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. [PLoS One] Full Article Integrated and Functional Genomics Analysis Validates the Relevance of the Nuclear Variant ErbB380kDa in Prostate Cancer Progression The nuclear localization of ErbB3 has been reported in various cancer tissues and cell lines but the nuclear functions and the putative correlation with tumor progression and resistance to therapy remain unclear. Researchers first assessed ErbB3 expression in normal and tumor prostate tissues. [PLoS One] Full Article CLINICAL RESEARCH Phase II Trial of Weekly Docetaxel, Zoledronic Acid, and Celecoxib for Castration-Resistant Prostate Cancer Investigators conducted a Phase II, open label, multinational prospective trial to evaluate the efficacy of weekly Docetaxel combined with Zoledronic acid and Celecoxib. [Invest New Drugs] Abstract |