Prostate Cell News Volume 8.33 | Sep 1 2017

TOP STORY

Moving towards Precision Urologic Oncology: Targeting Enzalutamide-Resistant Prostate Cancer and Mutated Forms of the Androgen Receptor Using the Novel Inhibitor Darolutamide (ODM-201)

Scientists evaluated the activity of darolutamide in enzalutamide-resistant castration resistant prostate cancer as well as in androgen receptor (AR) mutants detected in patients after treatment with enzalutamide, abiraterone, or bicalutamide. Darolutamide significantly inhibited cell growth and AR transcriptional activity in enzalutamide-resistant MR49F cells in vitro, and led to decreased tumor volume and serum prostate-specific antigen levels in vivo, prolonging survival in mice bearing enzalutamide-resistant MR49F xenografts. [Eur Urol] Full Article

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Synthetic Lethality between Androgen Receptor Signaling and the PARP Pathway in Prostate Cancer

The authors demonstrated a direct requirement for the androgen receptor to maintain homologous recombination (HR) gene expression and HR activity in prostate cancer. They showed that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy. [Nat Commun] Full Article

Manumycin A Suppresses Exosome Biogenesis and Secretion via Targeted Inhibition of Ras/Raf/ERK1/2 Signaling and hnRNP H1 in Castration-Resistant Prostate Cancer Cells

Manumycin-A (MA), a natural microbial metabolite, was identified as an inhibitor of exosome biogenesis and secretion by castration-resistant prostate cancer (CRPC) C4-2B, but not the normal RWPE-1, cells. While no effect was observed on cell growth, MA attenuated endosomal sorting complex required for transport-0 proteins hepatocyte growth factor-regulated tyrosine kinase substrate, ALG-2 interacting protein X and Rab27a and exosome biogenesis and secretion by CRPC cells. [Cancer Lett] Abstract

The Oncogenic Role of the In1-Ghrelin Splicing Variant in Prostate Cancer Aggressiveness

In1-ghrelin, but not native-ghrelin, was overexpressed in high-risk prostate-cancer (PCa)-samples compared to normal-prostate, and this expression correlated with that of PSA. Conversely, GHSR1a/1b expression was virtually absent. Plasmatic In1-ghrelin, but not native-ghrelin, levels were also higher in PCa-patients compared to healthy-controls. [Mol Cancer] Full Article

Pathway-Based Expression Profiling of Benign Prostatic Hyperplasia and Prostate Cancer Delineates an Immunophilin Molecule Associated with Cancer Progression

A differential gene expression study was conducted using biopsies from CaP and benign prostatic hyperplasia patients to identify the components putatively responsible for reinstating androgen receptor activity in CaP. Expression of FK506 binding protein 4 was positively correlated with that of c-Myc. [Sci Rep] Full Article

Lemur Tyrosine Kinase-3 Suppresses Growth of Prostate Cancer via the AKT and MAPK Signaling Pathways

Researchers determined the expression of lemur tyrosine kinase (LMTK)-3 in prostate cancer using immunohistochemistry and Western blotting. They infected PC3 and LNCaP cells with lentivirus-LMTK-3 and observed the biologic characteristics of the PC3 and LNCaP cells in vitro with TUNEL, and migration and invasion assays, respectively. [Cell Physiol Biochem] Full Article

Estradiol Promotes Epithelial-to-Mesenchymal Transition in Human Benign Prostatic Epithelial Cells

Estradiol (E2)-induced epithelial-to-mesenchymal transition (EMT) was observed both in 2D and 3D culture, with related regulation of EMT markers expression at both mRNA and protein level. E2 down-regulated luminal cell type markers CK18 and CK8 and up-regulated basal cell type markers CK5 and CK14. [Prostate] Abstract

PSCA Regulates IL-6 Expression through p38/NF-κB Signaling in Prostate Cancer

Investigators explored the regulating role of prostate stem cell antigen (PSCA) gene expression in interleukin-6 (IL-6) autocrine of PCa cells. The results showed that stable knockdown of PSCA delayed proliferation, migration, and invasion while overexpressing PSCA enhanced the proliferation, migration, and invasion in vitro and the lung metastasis in vivo of PCa cells. [Prostate] Abstract

CLINICAL RESEARCH

Intraprostatic Botulinum Toxin Type "A" Injection in Patients with Benign Prostatic Hyperplasia and Unsatisfactory Response to Medical Therapy: A Randomized, Double-Blind, Controlled Trial Using Urodynamic Evaluation

The authors evaluated the effectiveness of botulinum neurotoxin A in treating patients with benign prostatic hyperplasia unresponsive to combined medical therapy using urodynamic investigations. All patients in the intervention group reported subjective improvement starting after one month. [Neurourol Urodyn] Abstract

Managing High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Glands on Prostate Biopsy

Research efforts over the past few years have aimed to establish a more universal approach to management according to pathological grading; however, HGPIN and atypical glands suspicious for carcinoma are two diagnoses without standardized follow-up and treatment pathways. [Nat Rev Urol] Abstract

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Tyme Inc. to Present Prostate Cancer Data from Its Ongoing Phase II Trial for SM-88

Tyme Inc. announced that it will present data from its ongoing Phase II clinical trial evaluating investigational drug candidate, SM-88, for the treatment of recurrent, non-metastatic prostate cancer. [Press release from Tyme Inc. discussing research to be presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release

Astellas to Present New Data for Enzalutamide and IMAB362

Astellas announced that a wide selection of abstracts highlighting the company’s diverse oncology portfolio across a broad range of cancers will be presented. Key highlights from the Astellas Oncology portfolio include new analysis of enzalutamide data in men with metastatic castration-resistant prostate cancer and preclinical and clinical data for IMAB362, a compound from the recently acquired Ganymed, in gastric and pancreatic cancer. [Press release from Astellas (PR Newswire Association LLC.) discussing research to be presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release

Bayer to Showcase Latest Oncology Research

Bayer announced the latest research from across its growing oncology portfolio that will be presented. The studies presented will include new preclinical and clinical data on already approved or late-stage compounds as well as research from two earlier pipeline projects. [Press release from Bayer discussing research to be presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release

OncBioMune to Present Abstract on Clinical Trial of Novel Prostate Cancer Vaccine

OncBioMune Pharmaceuticals, Inc. announced that Dr. Jonathan Head, Chief Executive Officer and Chairman at OncBioMune, will be presenting an abstract. [Press release from OncBioMune Pharmaceuticals, Inc. discussing research to be presented at the 2017 American Association of Cancer Research (AACR) Special Conference, Boston] Press Release

Outstanding Investigator Grant Awarded to Dario C. Altieri, M.D., Wistar President and CEO

The Wistar Institute announced that distinguished scientist Dario C. Altieri, M.D., Wistar president and CEO and director of the Institute’s Cancer Center, has been awarded an Outstanding Investigator Grant by the National Institutes of Health for high-caliber research exploring “tumor plasticity.” This highly coveted NCI program grant totals nearly $8 million over seven years. [The Wistar Institute] Press Release

Dr. Peter Glazer Receives Prestigious Outstanding Investigator Award for Cancer Research

The National Cancer Institute has named Peter M. Glazer, M.D., Ph.D., as a recipient of its Outstanding Investigator Award. Glazer is the Robert E. Hunter Professor of Therapeutic Radiology, professor of genetics and chairman of the department of Therapeutic Radiology at Yale School of Medicine and Yale Cancer Center. [Yale School of Medicine] Press Release

OncBioMune Awaits Approval from Regulatory Committee to Commence Phase II Trial of ProscaVax as Front Line Prostate Cancer Treatment

OncBioMune Pharmaceuticals, Inc. reported that the protocol for the planned Phase II study of ProscaVax for early-stage prostate cancer is now under review by the Regulatory Committee at Beth Israel Deaconess Medical Center/Harvard Medical School, the host hospital network for the study. [OncBioMune Pharmaceuticals, Inc.] Press Release

Science Suffers as China’s Internet Censors Plug Holes in Great Firewall

China is tightening the screws on internet access, again. The latest crackdown—an evolving effort to ban virtual private networks not under government control—could seriously erode scientists’ ability to stay connected with peers abroad. [ScienceInsider] Editorial

Statement from FDA Commissioner Scott Gottlieb, M.D. on the FDA’s New Policy Steps and Enforcement Efforts to Ensure Proper Oversight of Stem Cell Therapies and Regenerative Medicine

The FDA has taken steps in Florida and California to address a number of especially troubling products being marketed. But unfortunately, these are examples of a larger pool of actors who claim that their unproven and unsafe products will address a serious disease, but instead put patients at significant risk. [U.S. Food and Drug Administration] Editorial

FDA Warns US Stem Cell Clinic of Significant Deviations

The FDA posted a warning letter issued to US Stem Cell Clinic of Sunrise, Florida, and its Chief Scientific Officer Kristin Comella for marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements, including some that could impact the sterility of their products, putting patients at risk. [U.S. Food and Drug Administration] Editorial

NEW 38^th Annual Ralph E. Hopkins Urology Seminar
February 7-11, 2018
Jackson Hole, Wyoming, United States

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NEW Research Assistant – Prostate Cancer (University College Dublin)

Postdoctoral Position – Molecular Imaging for Therapy Assessment in Prostate Cancer (Technische Universität München)

Postdoctoral Scientist – Prostate Cancer (Medical Research Council Laboratory of Molecular Biology)

Postdoctoral Position – Prostate Cancer (Moffitt Cancer Center)

Postdoctoral Research Fellow – Prostate Cancer (Edith Cowan University)

Postdoctoral Fellowship – Translational Cancer Disparities Research (Duke Cancer Institute)

Postdoctoral Research Associate – Prostate Cancer (University of South Carolina)

Postdoctoral Position – Prostate Cancer (Baylor College of Medicine)

Postdoctoral Scholar Position – Prostate Cancer (Case Western Reserve University)

Postdoctoral Position – Prostate Related Diseases (Baylor College of Medicine)

Assistant Member – Prostate Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Drug Discovery (Vancouver Prostate Centre)

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