Volume 4.21 | Jun 7

Prostate Cell News 4.21 June 7, 2013
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Zbtb7a Suppresses Prostate Cancer through Repression of a Sox9-Dependent Pathway for Cellular Senescence Bypass and Tumor Invasion
Scientists showed that ZBTB7A physically interacts with SOX9 and functionally antagonizes its transcriptional activity on key target genes such as MIA, which is involved in tumor cell invasion, and H19, a long noncoding RNA precursor for an RB-targeting microRNA. Inactivation of Zbtb7a in vivo leads to Rb downregulation, Pten loss-induced cellular senescence bypass and invasive prostate cancer. [Nature Genet] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)


An Androgen Receptor N-Terminal Domain Antagonist for Treating Prostate Cancer
Scientists investigated EPI-001, a small-molecule antagonist of androgen receptor (AR) N-terminal domain (NTD) that inhibits protein-protein interactions necessary for AR transcriptional activity. They found that EPI analogs covalently bound the NTD to block transcriptional activity of AR and its splice variants and reduced the growth of castration-resistant prostate cancer xenografts. [J Clin Invest]
Full Article | Press Release

99mTc-Labeled Small-Molecule Inhibitors of Prostate-Specific Membrane Antigen for Molecular Imaging of Prostate Cancer
Researchers evaluated preclinically four novel 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen (PSMA) with the potential for clinical translation for molecular imaging of prostate cancer in humans. High-affinity, saturable binding to PSMA on LNCaP cells was observed. [J Nucl Med] Abstract

Cancer-Associated Fibroblasts and M2-Polarized Macrophages Synergize during Prostate Carcinoma Progression
The authors demonstrated that stromal tumor-associated cells cooperate to favor malignancy of prostate carcinoma. Indeed, prostate cancer-associated fibroblasts are active factors of monocyte recruitment toward tumor cells, mainly acting through stromal-derived growth factor-1 delivery and promote their trans-differentiation toward the M2 macrophage phenotype. [Oncogene] Abstract

Loss of Caveolin-1 in Prostate Cancer Stroma Correlates with Reduced Relapse-Free Survival and Is Functionally Relevant to Tumor Progression
Silencing of Caveolin-1 (Cav-1) by shRNA in WPMY-1 prostate fibroblasts resulted in upregulation of Akt phosphorylation, and significantly altered expression of genes involved in angiogenesis, invasion and metastasis, including a >2.5-fold increase in TGF-β1 and γ-synuclein gene expression. Moreover, silencing of Cav-1 induced migration of prostate cancer cells when stromal cells were used as attractants. [J Pathol] Abstract

Notch3 Is Activated by Chronic Hypoxia and Contributes to the Progression of Human Prostate Cancer
Investigators report that in a hormone-sensitive prostate cancer cell line, LNCaP, Notch3 was activated by hypoxia and sustained cell proliferation and colony formation in soft agar. [Int J Cancer] Abstract

TRPV2 Mediates Adrenomedullin Stimulation of Prostate and Urothelial Cancer Cell Adhesion, Migration and Invasion
Researchers showed that adrenomedullin induces prostate and urothelial cancer cell migration and invasion through TRPV2 translocation to plasma membrane and the subsequent increase in resting calcium level. [PLoS One] Full Article

Fludarabine Treatment Favors the Retention of miR-485-3p by Prostate Cancer Cells: Implications for Survival
Scientists showed that a set of prostate cancer secretory microRNAs (miRNAs) were spontaneously released in the growth medium by DU-145 prostate cancer cells and the release was greater after treatment with the cytotoxic drug fludarabine. [Mol Cancer]
Abstract | Full Article

Enrichment of Putative Prostate Cancer Stem Cells after Androgen Deprivation: Upregulation of Pluripotency Transactivators Concurs with Resistance to Androgen Deprivation in LNCaP Cell Lines
Human prostate cancer lines LNCaP, LAPC4 and LAPC9 were depleted of androgen in cell cultures and in castrated SCID mice. The resultant androgen deprivation-resistant or castration-resistant populations, in particular in LNCaP and its derivative cell lines, displayed increased expression of pluripotency transactivators and significantly higher tumorigenicity. [Prostate] Abstract

Role of EZH2 in the Growth of Prostate Cancer Stem Cells Isolated from LNCaP Cells
Scientists investigated the effects of enhancer of zeste homolog 2 (EZH2) on prostate cancer stem cells (PCSCs). The results showed that LNCaP cell line comprised a greater proportion of CD44+/CD133+ cells by comparison to the PC-3 cell line. EZH2 was up-regulated in PCSCs compared with non-PCSCs. [Int J Mol Sci]
Abstract | Full Article


A Co-Clinical Approach Identifies Mechanisms and Potential Therapies for Androgen Deprivation Resistance in Prostate Cancer
Investigators report an integrated analysis that leverages data from treatment of genetic mouse models of prostate cancer along with clinical data from patients to elucidate new mechanisms of castration resistance. They showed that castration counteracts tumor progression in a Pten loss-driven mouse model of prostate cancer through the induction of apoptosis and proliferation block. [Nature Genet] Abstract

Phase II Trial of Neoadjuvant Docetaxel and CG1940/CG8711 Followed by Radical Prostatectomy in Patients with High-Risk Clinically Localized Prostate Cancer
Prostate cancer (PC), which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for PC is a cellular immunotherapy, composed of PC-3 cells and LNCaP cells. The authors report that six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. [Oncologist] Abstract

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Defining the Threshold for Significant versus Insignificant Prostate Cancer
Autopsy studies have shown the presence of a large reservoir of latent prostate cancers in adult men. Serum PSA testing of asymptomatic men leads to the detection of a proportion of these latent prostate cancers. The unequivocal demonstration of a substantial (30-50%) risk of overdiagnosis by the two largest randomized population-based screening trials has led to a growing awareness of this unwanted effect. [Nat Rev Urol] Abstract

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Aeterna Zentaris: Encouraging Final Data for Phase I Portion of Ongoing Phase I/II Trial with Zoptarelin Doxorubicin (AEZS-108) in Prostate Cancer Reported at ASCO
Aeterna Zentaris Inc. announced that final data for the Phase I portion of the ongoing Phase I/II trial with its lead oncology compound, zoptarelin doxorubicin, demonstrated the compound’s promising anti-tumor activity in heavily pre-treated men with castration- and taxane-resistant prostate cancer. [Press release from Aeterna Zentaris Inc. discussing research presented at the American Society of Clinical Oncology’s (ASCO) Annual Meeting, Chicago] Press Release

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Genspera Receives Patent on Targeted Prostate Cancer Drugs
GenSpera, Inc. announced that the United States Patent and Trademark Office issued patent 8,450,280 “Activation of Peptide Prodrugs by HK2.” The patent covers the composition of a series of prodrugs activated by HK2 to deliver a thapsigargin derivative selectively to prostate cancers. [GenSpera, Inc.]
Press Release

Isis Pharmaceuticals Earns $10 Million Milestone Payment from AstraZeneca for ISIS-AR Rx to Treat Prostate Cancer
Isis Pharmaceuticals, Inc. announced that AstraZeneca has added a second development candidate, ISIS-ARRx, to its collaboration with Isis. Isis earned a $10 million milestone payment associated with this decision. ISIS-ARRx is an antisense drug designed to treat patients with prostate cancer by inhibiting the production of the androgen receptor. [Isis Pharamaceuticals, Inc.] Press Release

Prostate Cancer Foundation and Major League Baseball Team Up Against Prostate Cancer
Major League Baseball and teams across the country are once again stepping up to the plate to hit home runs for prostate cancer research and encourage fans to Keep Dad in the Game as part of the 18th annual Home Run Challenge. The program, coordinated by the Prostate Cancer Foundation, will take place during the 16 days leading up to June 16-Fathers’ Day-and will help raise crucial awareness for prostate cancer and much needed research funding. [Prostate Cancer Foundation] Press Release


National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)


NEW The European Cancer Congress (ECCO) 2013
September 27 – October 1, 2013
Amsterdam, Netherlands

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NEW Director of Cell Processing Facility (S L Collins Associates, Inc.)

NEW Postdoctoral Research Scientist – Prostate Cancer Vaccine Development (Nuffield Department of Clinical Medicine, The Jenner Institute)

Postdoctoral Position – Mechanisms that Govern Prostate Cancer Progression (University of Copenhagen)

Postdoctoral Position – Castrate Resistant Prostate Cancer (Mount Sinai School)

PCUK Funded PhD Studentship – Prostate Cancer (Barts Cancer Institute, Queen Mary University of London)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

PhD Studentship – Investigation into Chemokine Receptor Induced Cell Migration (University of East Anglia)

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