Prostate Cell News Volume 8.21 | Jun 9 2017

TOP STORY

‘Once in a Career Feeling’ as Trial Shows Offering Prostate Cancer Drug Earlier Improves Survival

According to results from the Cancer Research UK-funded STAMPEDE clinical trial, offering abiraterone plus prednisolone in combination with standard therapy to men with prostate cancer earlier, before the disease becomes resistant to standard hormone therapy, can help boost survival. [Press release from the Cancer Research UK discussing online prepublication in The New England Journal of Medicine] Press Release | Full Article | Press Release 2

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

DNA Methylation Variations Are Required for Epithelial-to-Mesenchymal Transition Induced by Cancer-Associated Fibroblasts in Prostate Cancer Cells

Widespread genome hypo-methylation and promoter hyper-methylation of epithelium-specific genes are hallmarks of stable epithelial-to-mesenchymal transition (EMT), which in prostate cancer (PCa) correlates with castration resistance, cancer stem cells generation, chemoresistance and worst prognosis. Exploiting their consolidated ex-vivo system, scientists showed that cancer-associated fibroblasts released factors had pivotal roles in inducing genome methylation changes required for EMT and stemness in EMT-prone PCa cells. [Oncogene] Abstract

Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer

Histone acetylation readers such as bromodomain-containing protein 4 have been shown to associate with transcription factors and contribute to aggressive cancers including prostate cancer. Researchers showed that chromatin accessibility defines castration-resistant prostate cancer. They showed that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins mediate this effect. [Cell Rep] Full Article | Graphical Abstract

Development of Protein Degradation Inducers of Androgen Receptor by Conjugation of Androgen Receptor Ligands and Inhibitor of Apoptosis Protein (IAP) Ligands

Scientists developed hybrid molecules named specific and non-genetic inhibitor of IAP-dependent protein erasers (SNIPERs) that recruit IAP ubiquitin ligases to degrade target proteins. They showed that novel SNIPERs are capable of inducing proteasomal degradation of the androgen receptor. [J Med Chem] Abstract

Inhibition of Autophagy Prevents Cadmium-Induced Prostate Carcinogenesis

Cadmium, an established carcinogen, is a risk factor for prostate cancer. Researchers investigated the ability of psoralidin, a non-toxic, orally bioavailable compound to inhibit cadmium-induced autophagy to prevent prostate cancer. Psoralidin was studied using cadmium-transformed prostate epithelial cells, which exhibit high proliferative, invasive and colony forming abilities. [Br J Cancer] Abstract

Inhibition of Androgen Receptor Promotes CXC-Chemokine Receptor 7-Mediated Prostate Cancer Cell Survival

The authors investigated the role of androgen receptor (AR) in regulating CXC chemokine receptor 7 (CXCR7). Androgen deprivation or AR inhibition significantly increased CXCR7 expression in androgen-responsive prostate cancer cell lines, which was accompanied by enhanced epidermal growth factor receptor-mediated mitogenic signaling, promoting tumor cell survival through an androgen-independent signaling program. [Sci Rep] Full Article

Near Infrared Photoimmunotherapy Targeting Prostate Cancer with Prostate-Specific Membrane Antigen (PSMA) Antibody

PSMA is a membrane protein that is overexpressed manifold in prostate cancer and provides an attractive target for molecular therapy. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate. Investigators describe the efficacy of NIR-PIT, using a fully human IgG1 anti-PSMA monoclonal antibody, conjugated to the photo-absorber, IR700DX, in a PSMA expressing PC3 prostate cancer cell line. [Mol Cancer Res] Abstract

Upregulation of the Long Non-Coding RNA FALEC Promotes Proliferation and Migration of Prostate Cancer Cell Lines and Predicts Prognosis of PCa Patients

Investigators characterized the expression profile of FALEC in prostate cancer and paired histologically normal tissues. Additionally, biological function of FALEC in prostate cancer (PCa) cell lines was determined by in vitro and in vivo assays. [Prostate] Abstract

Whole-Genome Sequence of the Metastatic PC3 and LNCaP Human Prostate Cancer Cell Lines

Scientists report short-read whole-genome sequencing and de novo assembly of PC3 and LNCaP. A known homozygous mutation in TP53 and homozygous loss of PTEN were robustly identified in the PC3 cell line, whereas the LNCaP cell line exhibited a larger number of putative inactivating somatic point and indel mutations. [G3 (Bethesda)] Abstract

Combinatorial Treatment with Natural Compounds in Prostate Cancer Inhibits Prostate Tumor Growth and Leads to Key Modulations of Cancer Cell Metabolism

High-throughput screening of a natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer. Ursolic acid, curcumin and resveratrol was selected for further analyses and administered in vivo via the diet, either alone or in combination, in a mouse allograft model of prostate cancer. All possible combinations of these natural compounds produced synergistic effects on tumor size and weight, as predicted in the screens. [npj Precis Oncol] Full Article | Press Release

CLINICAL RESEARCH

Adult Prostatic Sarcoma: A Contemporary Multicenter Rare Cancer Network Study

Researchers report results of a large multicentric contemporary cohort of prostatic sarcoma (PS) patients. They included 61 adult PS patients treated in 16 American and European Institutions. Curative surgery was delivered in 48 patients, usually with lymphadenectomy. Curative radiotherapy was delivered in 32 patients, as radical, neoadjuvant, or postoperative treatment. [Prostate] Abstract

27-Hydroxycholesterol: A Novel Player in Molecular Carcinogenesis of Breast and Prostate Cancer

The authors highlight recent findings pertaining to the role of 27-hydroxycholesterol in breast cancer and prostate cancer and delineate the signaling mechanisms involved in the governing of different facets of tumor biology. [Chem Phys Lipids] Abstract

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

Zenith Announces Issuance of Patent for ZEN-3694 and Presentation Details

Zenith Capital Corp. announced that a patent covering its clinical compound, ZEN-3694, has been issued by the United States Patent and Trademark Office. ZEN-3694, a small molecule BET bromodomain inhibitor, is in clinical development for metastatic castrate resistant prostate cancer as a single agent and in combination with enzalutamide. [Press release from Zenith Epigenetics Ltd. discussing research to be presented at BIO International Convention, San Diego] Press Release

Astellas and Pfizer Announce Amendment to Clinical Research Protocol for Phase III PROSPER Trial of Enzalutamide in Patients with Non-Metastatic Castration-Resistant Prostate Cancer

Astellas Pharma Inc. announced the amendment of the protocol for the registrational PROSPER trial, a multi-national, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of XTANDI in patients with non-metastatic castration-resistant prostate cancer. [Astellas Pharma Inc.] Press Release

Sophiris Bio Announces that the First Patient Has Been Dosed in Phase IIb Study of Topsalysin in Patients with Clinically Significant Localized Prostate Cancer

Sophiris Bio Inc. announced that the first patient has been dosed in its Phase IIb study to evaluate the safety and tolerability of topsalysin in focally treating men with clinically significant localized prostate cancer. Topsalysin is an innovative, first-in-class pore-forming protein engineered to be activated only in the presence of enzymatically-active PSA, which is only found within the prostate. [Sophiris Bio Inc.] Press Release

UK Scientists Hope for Softened Brexit after Shock Election Result

The United Kingdom (UK)’s general election produced no clear outcome — but scientists trying to divine meaning from the chaos say they hope the result will ultimately benefit their country’s research ties with the European Union. [Nature News] Editorial

New Clues to Why a French Drug Trial Went Horribly Wrong

Scientists are one step closer to understanding how a clinical trial in France killed one volunteer and led to the hospitalization of five others. A new study shows that the compound tested in the study, BIA 10-2474, has effects on many other enzymes in addition to the one it was supposed to inhibit. These “off-target” effects might explain why the drug caused side effects ranging from headaches to irreversible brain damage. [ScienceInsider] Editorial

NEW 2017 The National Cancer Research Institute (NCRI) Cancer Conference
November 5-8, 2017
Liverpool, United Kingdom

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

NEW Postdoctoral Fellow – Prostate Cancer and Head & Neck Cancer (University of Maryland)

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

Postdoctoral Fellow – Drug Discovery (The Vancouver Prostate Centre)

Research Associate – Prostate Cancer (Meharry Medical College)

Assistant Professor – Prostate Cancer, Carcinogenesis and Chemoprevention, Advanced Tissue Imaging (University of Illinois at Chicago)

Pathology Clinical Research Fellow – Treatment of Men with Advanced Prostate Cancer (Institute of Cancer Research)

Postdoctoral Fellow – Androgen Action in Prostate Cancer (Lerner Research Institute, Cleveland Clinic)

Postdoctoral Fellow – Mammalian Stem Cell Biology (NYU School of Medicine)

Postdoctoral Fellow – Translational Prostate Cancer Research (Weill Cornell Medicine)

Postdoctoral Senior Fellow – Microbiology, Genetics, and Translational Prostate Cancer Research (University of Washington)

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