Prostate Cell News Volume 8.06 | Feb 17 2017

TOP STORY

An Exploratory Analysis of Alkaline Phosphatase, Lactate Dehydrogenase, and Prostate-Specific Antigen Dynamics in the Phase III ALSYMPCA Trial with Radium-223

The radium-223 ALSYMPCA trial enrolled patients with castration-resistant prostate cancer and symptomatic bone metastases. Prognostic potential of baseline variables was assessed using Cox models. [Ann Oncol] Abstract

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

MYC Mediates Large Oncosome-Induced Fibroblast Reprogramming in Prostate Cancer

Investigators describe a new mechanism of intercellular communication originating from large oncosomes (LO), which are cancer cell-derived, atypically large extracellular vesicles. They demonstrated that, in the context of prostate cancer, LO harbor sustained AKT1 kinase activity, nominating them as active signaling platforms. [Cancer Res] Full Article

Aberrant Corticosteroid Metabolism in Tumor Cells Enables GR Takeover in Enzalutamide Resistant Prostate Cancer

The authors showed that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, autocrine mobility factor receptor, mediating loss of 11β-hydroxysteroid dehydrogenase-2, which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate glucocorticoid receptor and enzalutamide resistance. [ELife] Full Article | Press Release

Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase

Investigators screened libraries of nonpurified resorcinol amide derivatives by surface plasmon resonance to determine the binding dissociation constant for compounds binding to the pyruvate dehydrogenase kinase enzyme. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro. [J Med Chem] Abstract | Graphical Abstract

Aurora A Regulates Expression of AR-V7 in Models of Castrate Resistant Prostate Cancer

Scientists investigated the role of Aurora A kinase on androgen receptor variants (AR-Vs) in models of castrate-resistant prostate cancer (CRPC) and showed depletion of Aurora A reduces AR-V target gene expression. Knockdown of Aurora A reconfigured splicing of AR pre-mRNA to discriminately down-regulate synthesis of AR-V transcripts, including AR-V7, without effecting full-length AR mRNA; and as a consequence, AR-V-driven proliferation and survival of CRPC cells was markedly reduced. [Sci Rep] Full Article

A Targeted Contrast Agent Specific to an Oncoprotein in Tumor Microenvironment with the Potential for Detection and Risk Stratification of Prostate Cancer with MRI

Researchers synthesized a peptide targeted contrast agent, ZD2-Gd(HP-DO3A), specific to an oncoprotein in tumor microenvironment, EDB-FN, for non-invasive detection and characterization of aggressive prostate cancer. The EDB-FN mRNA level in the metastatic PC3 cells was found to be over three times higher than that in non-metastatic LNCaP cells. [Bioconjug Chem] Abstract

Celastrol, an Active Constituent of the TCM Plant Tripterygium wilfordii Hook.f., Inhibits Prostate Cancer Bone Metastasis

Using a PC-3 cell model, investigators performed in vitro assays to evaluate the effects of celastrol on proliferation, migration, tissues invasion and vascular endothelial growth factor secretion. Pretreatment with celastrol significantly reduced proliferation of PC-3 cells in a dose-dependent manner and cell migration was much slower than in controls. [Prostate Cancer Prostatic Dis] Abstract

Anti-Proliferative Activities of Finasteride in Benign Prostate Epithelial Cells Require Stromal Fibroblasts and c-Jun Gene

The authors aimed to identify the role of mouse fibroblast-mediated c-Jun and IGF-1 signaling in the therapeutic effect of finasteride on benign prostatic epithelial cells. The in vitro results demonstrated that when BPH-1 cells were grown in monoculture, treatment with finasteride did not induce cell death and stimulated the expression of pro-proliferative signaling molecules, while in the presence of fibroblasts containing c-Jun, finasteride treatment repressed epithelial cell proliferation, the level of IGF-1 in the medium, and the activation of downstream pro-proliferative signaling pathways. [PLoS One] Full Article

RAB27A, RAB27B and VPS36 Are Downregulated in Advanced Prostate Cancer and Show Functional Relevance in Prostate Cancer Cells

The endosomal sorting complexes required for transport machinery and Rab-proteins act as key players in vesicular trafficking and secretion. Yet, their role in prostate cancer (PCa) is unknown. Investigators aimed to elucidate the relevance of these components in PCa. [Int J Oncol] Abstract

CLINICAL RESEARCH

Revisiting the Role of Wnt/β-Catenin Signaling in Prostate Cancer

Recent genome-wide analysis of prostate cancer metastases illustrate the importance of the Wnt/β-catenin pathway in prostate cancer and compelled the authors to reexamine the interaction of the androgen receptor and Wnt/β-catenin signaling pathways. This review includes newer areas of interest such as non-canonical Wnt signaling and the role of Wnts in prostate cancer stem cells. [Mol Cell Endocrinol] Abstract

Visit our reviews page to see a complete list of reviews in the prostate cell research field.

Arvinas Presents New Preclinical Data on Oral Androgen Receptor PROTAC

Arvinas LLC announced the presentation of new preclinical data on its oral androgen receptor PROTAC. The new data presented continues to validate their platform and the potential of PROTACs to drive durable and robust responses in important indications like castrate-resistant prostate cancer where inhibition can be effective yet short-lived. [Press release from Arvinas Inc. discussing research presented at the American Society of Clinical Oncology 2017 Genitourinary Cancers Symposium (ASCO GU), Orlando] Press Release

New Research Suggests Broader Genetic Testing of Prostate Cancer Patients May Be Warranted to Identify Risk of an Inherited Mutation that Might Inform Treatment

New research suggests that a substantial fraction of patients with prostate cancer and a positive family history are at high risk of an inherited genetic mutation that might help inform their treatment options. Among those men with prostate cancer meeting NCCN guidelines for testing, these initial data support the concept that particulars in the family history cannot be used to predict pathogenic variants. [Press release from Invitae Corporation discussing research presented at the American Society of Clinical Oncology 2017 Genitourinary Cancers Symposium (ASCO GU), Orlando] Press Release

CyberKnife^® System Provides Long-Term Disease Control for Prostate Cancer Patients

Accuray Incorporated announced data from a prospective, Phase II, 17-center study which showed that treatment with the CyberKnife^® System for low- and intermediate-risk prostate cancer provides excellent long-term results. At five years, the disease-free survival rate for low-risk prostate cancer patients was 100 percent and for intermediate-risk patients was 88.5 percent. [Press release from Accuray Incorporated discussing research presented at the American Society of Clinical Oncology 2017 Genitourinary Cancers Symposium (ASCO GU), Orlando] Press Release

Four New Studies of Oncotype DX^® Genomic Prostate Score™ (GPS) Reconfirm Value of Test in Guiding Early-Stage Prostate Cancer Risk Assessment and Treatment Selection

Genomic Health, Inc. announced the presentation of results from four studies evaluating the clinical value and utility of its Oncotype DX^® Genomic Prostate Score™ in the management of early-stage prostate cancer. Collectively, these new data highlight the test’s ability to predict disease aggressiveness and refine risk stratification across National Comprehensive Cancer Network clinical risk groups. [Press release from Genomic Health, Inc. discussing research presented at the American Society of Clinical Oncology 2017 Genitourinary Cancers Symposium (ASCO GU), Orlando] Press Release

Champions Oncology Announces New Collection of Patient-Derived Xenograft (PDX) Models Available for Translational Research

Champions Oncology, Inc. announced the addition of new cohorts of PDX models to their existing TumorBank. These new models will expand Champions’ product line in hepatocellular cancer, breast cancer, castrate resistant prostate cancer, head and neck cancer, AML, and non-small cell lung cancer PDX models. [Champions Oncology, Inc.] Press Release

Prostate Cancer Foundation Announces New Recipients of 2016 PCF Challenge Awards to Promote Research in Deadly Prostate Cancer

The Prostate Cancer Foundation (PCF) announced that it has granted eight new 2016 PCF Challenge Awards to advance treatments and cures for metastatic or currently incurable prostate cancer. [Prostate Cancer Foundation] Press Release

Stakeholders Applaud USPSTF for Including Urologist in Review Process for Updated Prostate Cancer Recommendations

As part of an ongoing commitment to maintaining patient access to prostate cancer screening, a coalition of physicians and patient groups applauded the decision by the U.S. Preventive Services Task Force to include a urologist to independently review the evidence report that will inform updated recommendations on prostate cancer screening. [American Urological Association] Editorial

Why the CRISPR Patent Verdict Isn’t the End of the Story

The US Patent and Trademark Office issued a key verdict this week in the battle over the intellectual property rights to the potentially lucrative gene-editing technique CRISPR–Cas9. [Nature News] Editorial

NEW Gordon Research Conference: Wnt Signaling
August 6-11, 2017
Stowe, United States

Visit our events page to see a complete list of events in the community.

NEW PhD Studentships – Translational Research Network for Prostate Cancer (University of Glasgow)

NEW Clinical Research Fellow – Oncogenetics (Institute of Cancer Research)

NEW Postdoctoral Researcher – Confocal Raman Spectroscopy and Digital Holographic Microscopy (Maynooth University)

Postdoctoral Fellow – RNA Biology (Thomas Jefferson University)

Professor/Associate Professor – Prostate Cancer Research (Lerner Research Institute)

Postdoctoral Researcher – Prostate Cancer Immunotherapy (University of Chicago)

Postdoctoral Fellow – Prostate Cancer Biology (Weill Cornell Medicine)

Postdoctoral Fellow – Prostate/Pancreatic Cancer (Medical College of Wisconsin)

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College / Geisel School of Medicine)

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