LABORATORY RESEARCH Secretory Leukocyte Protease Inhibitor Is a Survival and Proliferation Factor for Castration-Resistant Prostate Cancer Scientists provide the first evidence that secretory leukocyte peptidase inhibitor (SLPI) is upregulated in a subset of castration-resistant prostate cancer (CRPC) cell lines and CRPC patient tumors. In addition, serum SLPI levels are significantly elevated in metastatic CRPC patients compared with hormone naive patients, raising the possibility that this could serve as a biomarker. [Oncogene] Abstract P-Rex1 Promotes Resistance to VEGF/VEGFR-Targeted Therapy in Prostate Cancer Researchers observed that cancer stem cells (CSCs) isolated from prostate tumors are resistant to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapy. Resistance was mediated by VEGF/neuropilin signaling, which was not inhibited by bevacizumab and sunitinib, and it involves the induction of P-Rex1, a Rac GEF, and consequent Rac1-mediated ERK activation [Cell Rep] Full Article | Graphical Abstract The Essential Role of Methylthioadenosine Phosphorylase in Prostate Cancer Investigators report the near universal retention of methylthioadenosine phosphorylase (MTAP) expression in a panel of human prostate cancer cell lines as well as patient samples. Upon metabolic perturbation, prostate cancer cell lines upregulated MTAP and this correlated with recovery of SAM levels. [Oncotarget] Full Article Linneg Sca-1high CD49fhigh Prostate Cancer Cells Derived from the Hi-Myc Mouse Model Are Tumor-Initiating Cells with Basal-Epithelial Characteristics and Differentiation Potential In Vitro and In Vivo The authors established a cell line from ventral prostate (VP) tumors of one-year-old Hi-Myc mice. These cells, called HMVP2 cells, were LinnegSca-1highCD49fhigh with high CD44 and CD29 expression and express CK14, Sca-1 and CD49f (but not CK8), suggesting basal-epithelial characteristics. [Oncotarget] Full Article P38 MAPK Regulates the Wnt Inhibitor Dickkopf-1 in Osteotropic Prostate Cancer Cells Inhibition of p38 MAPK signaling in osteolytic PC3 cells by small molecule inhibitors suppressed Dickkopf-1 (DKK-1) expression, whereas activation of p38 MAPK by anisomycin increased DKK-1. Further dissection by targeting individual p38 MAPK isoforms with siRNA revealed a stronger role for MAPK11 than MAPK14 and MAPK12 in the regulation of DKK-1. [Cell Death Dis] Full Article Inhibition of AKT Promotes FOXO3a-Dependent Apoptosis in Prostate Cancer Researchers demonstrated that inhibition of protein kinase-B (PKB)/AKT facilitates nuclear shuttling of Forkhead box O-3a (FOXO3a) where it regulates pro-apoptotic response-4 (Par-4) transcription in castration-resistant prostate cancer (CRPC) cells. FOXO3a is upstream of Par-4 signaling, which is required for induction of apoptosis in CRPC. [Cell Death Dis] Full Article Targeting Fatty Acid Synthase with ASC-J9 Suppresses Proliferation and Invasion of Prostate Cancer Cells Investigators found that androgen-deprivation-therapy with anti-androgens Bicalutamide or Enzalutamide had little effect to suppress fatty acid synthase expression and FASN-mediated cell growth and invasion during the castration resistant stage when the androgen concentration is 1 nM dihydrotestosterone. [Mol Carcinog] Abstract CLINICAL RESEARCH Phytotherapeutic Interventions in the Management of Biochemically Recurrent Prostate Cancer: A Systematic Review of Randomized Trials The authors evaluated the evidence from randomized trials for the efficacy and safety of phytotherapeutic interventions in the management of biochemically recurrent prostate cancer, indicated by prostate-specific antigen progression, numbers progressing to/time to initiation of androgen-deprivation therapy or salvage therapy. [BJU Int] Abstract Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer after Docetaxel Failure: A Randomized, Double-Blind, Placebo-Controlled Phase III Bridging Study Investigators evaluated the efficacy and safety of abiraterone acetate-prednisone versus placebo-prednisone in Asian metastatic castration-resistant prostate cancer patients who have failed docetaxel-based chemotherapy. [Int J Urol] Abstract |