Prostate Cell News Volume 10.05 | Feb 15 2019

TOP STORY

DNA Hypermethylation Encroachment at CpG Island Borders in Cancer Is Predisposed by H3K4 Monomethylation Patterns

Scientists showed that the pattern of H3K4me1 at CpG island borders in normal cells predicted the different modes of cancer CpG island hypermethylation. Notably, genetic manipulation of Kmt2d resulted in concordant alterations in H3K4me1 levels and CpG island border DNA methylation encroachment. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer

Researchers showed in androgen receptor (AR) v7-dependent castration-resistant prostate cancer models that ARv7 bound together with full-length AR to repress transcription of a set of growth-suppressive genes. [Cancer Cell] Abstract | Graphical Abstract

Loss of Foxp3 and Tsc1 Accelerate Prostate Cancer Progression through a Synergistic Transcriptional and Post-Translational Regulation of c-MYC

Scientists characterized the functional crosstalk between FOXP3-c-MYC and TSC1-mTOR signaling during tumor progression. Deletion of Tsc1 in mouse embryonic fibroblasts decreased phosphorylation of c-MYC at threonine 58 and increased phosphorylation at serine 62, an observation validated in prostate cancer cells. [Cancer Res] Abstract

Prostate Cancer Promotes a Vicious Cycle of Bone Metastasis Progression through Inducing Osteocytes to Secrete GDF15 that Stimulates Prostate Cancer Growth and Invasion

The authors explored the crosstalk between prostate cancer (PCa) cells and osteocytes (OCys) to determine if it contributes to PCa progression. PCa cells induced OCys to promote PCa proliferation, migration and invasion. [Oncogene] Abstract

Inhibition of Karyopherin Beta 1 Suppresses Prostate Cancer Growth

Investigators report that KPNB1, a key member of Karyopherin beta subunits, was highly expressed in advanced prostate cancers. Further study showed that targeting KPNB1 suppressed the proliferation of prostate cancer cells. [Oncogene] Abstract

Essential Role of JunD in Cell Proliferation Is Mediated via MYC Signaling in Prostate Cancer Cells

Comparative integrative analysis by ingenuity pathway analysis identified cell cycle control/regulation as the top canonical pathway whose members exhibited a significant decrease in their expression following JunD knock-down including PRDX3, PEA15, KIF2C, and CDK2, and JunD dependent genes were associated with cell proliferation, with MYC as the key downstream regulator. [Cancer Lett] Abstract

Critical Role of H₂O₂ in Mediating Sanguinarine-Induced Apoptosis in Prostate Cancer Cells via Facilitating Ceramide Generation, ERK1/2 Phosphorylation, and Par-4 Cleavage

Scientists demonstrated that sanguinarine (SNG) has potent anti-proliferative activity against prostate cancer cells. They suggest that SNG induces ceramide (Cer) generation via inhibiting acid ceramidase and glucosylceramide synthase, two important enzymes involved in Cer metabolism. [Free Radic Biol Med] Abstract | Graphical Abstract

Therapeutic Targeting of CD146/MCAM Reduces Bone Metastasis in Prostate Cancer

Researchers investigated the function of MCAM in a direct co-culture model of human prostate cancer (PCa) cells with human osteoblasts and found that there was reduced influence of human osteoblasts on human PCa cells in which MCAM has been knocked down. [Mol Cancer Res] Abstract

The RNA-Binding Protein FXR1 Modulates Prostate Cancer Progression by Regulating FBXO4

The authors observed aberrant overexpression of fragile X mental retardation, autosomal homolog 1 (FXR1) in prostate cancer cells at both transcript and protein levels. FXR1 deficiency was associated with inhibited cell proliferation/viability and compromised migration/invasion in prostate cancer cells. [Funct Integr Genomics] Abstract

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Obesity, Inflammation, and Prostate Cancer

Inflammatory cells play important roles in tumor progression. A high-fat diet or obesity changes the local profile of immune cells, such as myeloid-derived suppressor cells and macrophages, in prostate cancer. [J Clin Med] Full Article

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Merck Increases Focus on Advanced Prostate Cancer, Expanding Immuno-Oncology Program with Three New Phase III Trials

Merck announced the presentation of interim data from the Phase Ib/II KEYNOTE-365 umbrella trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with various agents for the treatment of patients with metastatic castration-resistant prostate cancer. [Press release from Merck discussing research presented at the 2019 Genitourinary Cancers Symposium (ASCO GU), San Francisco] Press Release

Trovagene Presents Update on Phase II Study of Onvansertib in Combination with Zytiga in Patients with mCRPC

Trovagene, Inc. presented an overview of its ongoing Phase II study evaluating Onvansertib in combination with Zytiga^®/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). [Press release from Trovagene, Inc. discussing research presented at the 2019 Genitourinary Cancers Symposium (ASCO GU), San Francisco] Press Release

Veru Announces Scientific Presentations for Novel Prostate Cancer Drug Candidates

Veru Inc. announced that four presentations relating to Veru drug candidates are being given. [Press release from Veru Inc. discussing research presented at the 2019 Genitourinary Cancers Symposium (ASCO GU), San Francisco] Press Release

TYME Reports Encouraging SM-88 Clinical Results without Typical Hormone-Related Side Effects in Phase II Study of Patients with Biomarker Recurrent Prostate Cancer

Tyme Technologies, Inc. announced encouraging preliminary results from an ongoing Phase II trial of SM-88 in patients with non-metastatic, biochemical-recurrent prostate cancer. [Press release from Tyme Technologies, Inc. discussing research presented at the 2019 Genitourinary Cancers Symposium (ASCO GU), San Francisco] Press Release

New Clinical Data Analysis Shows Survival Benefit Three Years after Treatment with Sipuleucel-T

Dendreon Pharmaceuticals LLC released results of a new retrospective analysis of clinical trial data showing a long-lasting survival benefit three years after treatment with PROVENGE^® in men with metastatic castrate-resistant prostate cancer. [Press release from TDendreon Pharmaceuticals LLC (Business Wire, Inc.) discussing research presented at the 2019 Genitourinary Cancers Symposium (ASCO GU), San Francisco] Press Release

Phase III ARCHES Trial Shows XTANDI^® (Enzalutamide) Significantly Improved Radiographic Progression-Free Survival in Men with Metastatic Hormone-Sensitive Prostate Cancer

Pfizer Inc. and Astellas Pharma Inc. announced results from the Phase III ARCHES trial in men with metastatic hormone-sensitive prostate cancer. [Press release from Pfizer Inc. discussing research presented at the 2019 Genitourinary Cancers Symposium (ASCO GU), San Francisco] Press Release

Opdivo (Nivolumab) plus Yervoy (Ipilimumab) Shows Response in Pre-Treated Patients with Metastatic Castration-Resistant Prostate Cancer

Bristol-Myers Squibb Company announced data evaluating Opdivo in combination with Yervoy in patients with metastatic castration-resistant prostate cancer. [Press release from Bristol-Myers Squibb Company discussing research presented at the 2019 Genitourinary Cancers Symposium (ASCO GU), San Francisco] Press Release

Janssen Announces Preliminary Results from Phase II GALAHAD Study in Adults with Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Pathway Defects (DRD)

The Janssen Pharmaceutical Companies of Johnson & Johnson will present early results from the ongoing Phase II GALAHAD study evaluating niraparib, a poly (ADP-ribose) polymerase inhibitor, in patients with metastatic castration-resistant prostate cancer and DRD. [Press release from The Janssen Pharmaceutical Companies discussing research presented at the 2019 Genitourinary Cancers Symposium (ASCO GU), San Francisco] Press Release

AIVITA Identifies Mechanism to Enhance Patient Response Rate to Next Generation Cancer Stem Cell Immunotherapy

AIVITA announced new data indicating that non-responders to its immunotherapy had, on average, 150,000 times more pre-existing PD-1 proteins in their bloodstreams than responders. These findings suggest a means to optimize patient inclusion criteria in AIVITA’s trials evaluating ROOT OF CANCER. [AIVITA Biomedical] Press Release

Hungary’s Scientists Outraged by Government Budget Grab

In the cold afternoon sunshine of 12 February, hundreds of scientists and their supporters formed a human chain around the historic Hungarian Academy of Sciences building in Budapest. The gesture was one of protection. Inside, academy members were holding an emergency meeting to decide how to handle what they say is a serious a threat to the nation’s science community. [Nature News] Editorial

Indian Payment-for-Papers Proposal Rattles Scientists

Indian scientists are criticizing a government proposal to pay graduate students who publish in select journals. They fear that it could degrade the quality of research and lead to an increase in scientific misconduct, by incentivizing publishing rather than good science. [Nature News] Editorial

NEW 3^rd SUNRiSE Meeting : New Advances in Cancer Stem Cells
May 16-17, 2019
Nice, France

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NEW Research Assistant II – Cancer Biology (MD Anderson Cancer Center)

Senior Computational Biologist – Molecular Oncology (Cancer Research UK Manchester Institute)

Postdoctoral Positions – Stem Cell and Cancer Biology (Columbia University Irving Medical Center)

Postdoctoral Fellow – Cancer Biology (Thomas Jefferson University)

Assistant Professor – Translational Cancer Research (Texas Tech University Health Sciences Center El Paso)

Postdoctoral Position – Prostate Cancer (University of Trento)

Postdoctoral Fellow – Prostate Cancer & Stem Cell Biology (City of Hope)

Faculty Position – Radiation Oncology & Molecular Radiation Sciences (Johns Hopkins University)

Postdoctoral Fellow – Cancer Immunotherapy (University of Notre Dame)

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