Prostate Cell News Volume 3.38 | Oct 5 2012

E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation
To identify novel oncogenic E3 ubiquitin ligases as anti-cancer targets, scientists screened an E3 ubiquitin ligase siRNA library containing siRNA pools against 555 individual E3s using the SRB assay in the MDA-MB-231 breast cancer cell line and the PC3 prostate cancer cell line. [Cancer Res] Abstract

LABORATORY RESEARCH

Persistent Androgen Receptor-Mediated Transcription in Castration-Resistant Prostate Cancer under Androgen-Deprived Conditions
The authors explored androgen receptor (AR) function under the androgen-deprived conditions characteristic of castration-resistant prostate (CRPC). Their data demonstrate that AR persistently occupies a distinct set of genomic loci after androgen deprivation in CRPC. [Nucleic Acids Res] Full Article

CXCL1/GRO�� Increases Cell Migration and Invasion of Prostate Cancer by Decreasing Fibulin-1 Expression through NF-кB/Histone Deacetylase 1 Epigenetic Regulation
The authors investigated whether CXCL1/GRO�� enhances cell migration and invasion in PC-3 and DU145 castration-resistant prostate cancer. Induction of PC-3 and DU145 cancer progression by CXCL1/GRO�� is associated with increased AKT activation and IKKα phosphorylation, resulting in NF-кB activation. [Carcinogenesis] Abstract

Integrin-Linked Kinase as a Target for ERG-Mediated Invasive Properties in Prostate Cancer Models
ERG expression promotes prostatic epithelial dysplasia in transgenic mice, and acquisition of epithelial-to-mesenchymal transition (EMT) characteristics in human prostatic epithelial cells (PrECs). To explore whether ERG-induced EMT in PrECs was associated with therapeutically targetable transformation characteristics, researchers established stable populations of immortalized human PrEC lines that constitutively express Flag-tagged ERG3. [Carcinogenesis] Abstract

Vav3 Enhances Androgen Receptor Splice Variant Activity and Is Critical for Castration-Resistant Prostate Cancer Growth and Survival
Investigators examined the contributions of Vav3 to androgen receptor activity in two castration-resistant prostate cancer cell lines that naturally express relatively high levels of Vav3 and androgen receptor splice variant AR3. [Mol Endocrinol] Abstract

Activin A Stimulates AKR1C3 Expression and Growth in Human Prostate Cancer
Researchers investigated the effects of activin on intratumoral steroidogenesis in prostate cancer (PC). Activin A effects and regulation of the activin-signaling pathway molecules were studied in the PC cell lines LNCaP, VCaP, and PC-3 and in 13 individual PC xenograft models. [Endocrinology] Abstract

Estrogen Receptors β1 and β2 Have Opposing Roles in Regulating Proliferation and Bone Metastasis Genes in the Prostate Cancer Cell Line PC3
Using PC3 and 22Rv1 prostate cancer cell lines that stably express ER (estrogen receptor) β1 or ERβ2, scientists found that the ERβ variants differentially regulate genes known to affect tumor behavior. [Endocrinology] Abstract

Effects of Genetically Engineered Stem Cells Expressing Cytosine Deaminase and Interferon-Beta or Carboxyl Esterase on the Growth of LNCaP Prostate Cancer Cells
To develop a new prostate cancer therapy, researchers used a stem cell-derived gene directed prodrug enzyme system using human neural stem cells that have a tumor-tropic effect. The human stem cells were found to migrate toward LNCaP human prostate cancer cells rather than primary cells. [Int J Mol Sci] Abstract

c-Met Inhibitor SU11274 Enhances the Response of the Prostate Cancer Cell Line DU145 to Ionizing Radiation
Investigators demonstrated that c-Met inhibition could significantly suppress cell survival and proliferation as well as enhance the radiosensitivity of DU145 cells. [Biochem Biophys Res Commun] Abstract

TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases
Scientists showed that TET1 is downregulated in prostate and breast cancer tissues. TET1 depletion facilitates cell invasion, tumor growth, and cancer metastasis in prostate xenograft models and correlates with poor survival rates in breast cancer patients. [Cell Reports] Abstract | Graphical Abstract

CLINICAL RESEARCH

Phase I Study of Concurrent Weekly Docetaxel, High-Dose Intensity-Modulated Radiation Therapy and Androgen-Deprivation Therapy for High-Risk Prostate Cancer
Researchers evaluated in a phase I trial, the feasibility of adding concurrent weekly docetaxel chemotherapy to high-dose intensity modulated radiation therapy and androgen-deprivation therapy for treatment of high-risk prostate cancer. [BJU Int] Abstract

Two-Year Survival Follow-Up of the Randomized, Double-Blind, Placebo-Controlled Phase II Study of Radium-223 Chloride in Patients with Castration-Resistant Prostate Cancer and Bone Metastases
This phase II randomized, placebo-controlled study was conducted to evaluate efficacy and safety of radium-223 in patients with castration-resistant prostate cancer and painful bone metastases. [Clin Genitourin Cancer]

Abiraterone and Novel Antiandrogens: Overcoming Castration Resistance in Prostate Cancer
This article reviews current concepts and challenges behind targeting continued androgen receptor signaling in castration-resistant prostate cancer and provides an overview of recently completed and ongoing clinical trials of novel hormonal agents, with a focus on abiraterone acetate and enzalutamide. [Annu Rev Med] Abstract

Prostate Cancer- From Steroid Transformations to Clinical Translation
Abiraterone inhibits steroid 17α-hydroxylase/17,20-lyase and blocks androgen synthesis, whereas enzalutamide directly binds and antagonizes the androgen receptor. Both agents are highly effective against castration-resistant prostate cancer (CRPC) and significantly prolong survival following docetaxel treatment. However, the clinical validation of the androgen pathway has led to questions regarding the fundamental mechanisms of CRPC, as well as resistance to abiraterone and enzalutamide. [Nat Rev Urol] Abstract

Why Imatinib Remains an Exception of Cancer Research
To answer why imatinib remains an exception of cancer research, the authors summarize key features and patterns of evolution that contrast chronic phase chronic myeloid leukemia from prostate cancer, an example of a solid tumor that also shares a signature fusion gene. [J Cell Physiol] Abstract

Aeterna Zentaris Presented Poster on Oral Prostate Cancer Vaccine, AEZS-120
Aeterna Zentaris Inc. announced the presentation of the preclinical data on its oral prostate cancer vaccine candidate, AEZS-120. The presentation underlined the feasibility of an oral therapeutic vaccination approach against prostate cancer. [Press release from Aeterna Zentaris Inc. discussing data presented at the 32nd Congress of the Société Internationale d’Urologie, Fukuoka] Press Release | Poster

Tasquinimod Biomarker Phase II Data Presented at ESMO 2012
Active Biotech and Ipsen presented a new set of data on biomarkers from the previously concluded tasquinimod phase II study in chemotherapy-naïve metastatic castrate resistant prostate cancer. [Press release from Ipsen Group discussing data presented during the European Society for Medical Oncology (ESMO) 2012 Annual Meeting, Vienna] Press Release

Phase I/II ARADES Trial of a New Generation Anti-Androgen, ODM- 201
Researchers presented initial results from the phase I component of the Arades trial. ARADES trial is the first-in-man, open-label, phase I/II safety, pharmacokinetic, and proof-of-concept study of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer. [Press release from Orion Corporation discussing data presented at the European Society for Medical Oncology (ESMO) 2012 Congress, Vienna] Press Release

Preliminary Phase I Data for Cabozantinib in Japanese Patients
Exelixis, Inc. reported preliminary data from an ongoing phase I dose escalation study of cabozantinib in Japan. The primary objective of the phase I, open label, multiple cohort dose escalation study is to determine the recommended phase II dose of cabozantinib administered once-daily over a four-week cycle in Japanese patients with advanced or metastatic solid tumors. [Press release from Exelixis, Inc. discussing data presented at the European Society for Medical Oncology (ESMO) 2012 Congress, Vienna]
Press Release

Aragon Pharmaceuticals Raises $50 Million in Series D Financing to Advance Promising Therapeutic Candidates for Hormone-Driven Cancers
Aragon Pharmaceuticals Inc. announced that the company has raised $50 million in a Series D financing to advance the company’s pipeline of therapies targeting hormone-driven cancers, including ARN-509 for the treatment of castration-resistant prostate cancer. [Aragon Pharmaceuticals Inc.] Press Release

Ipsen Initiates a Phase II “Switch Maintenance” Trial in Metastatic Castrate-Resistant Prostate Cancer with Tasquinimod
Ipsen and Active Biotech announced the initiation of a new phase II proof of concept clinical trial, evaluating the activity of tasquinimod in advanced metastatic castrate resistant prostate cancer (CRPC) patients. The study aims at establishing the clinical efficacy of tasquinimod used as maintenance therapy in patients with metastatic CRPC who have not progressed after a first line docetaxel based chemotherapy. [Ipsen Group] Press Release

First Patient in Dendreon EU Open-Label Study Begins Sipuleucel-T Infusion Treatment
Dendreon Corporation announced the first patient enrollment and initiation of treatment for the sipuleucel-T European Union (EU) open-label study. The open-label study is being conducted in European men with metastatic castrate-resistant prostate cancer to describe product release parameters and report on safety in a European population. [Dendreon Corporation] Press Release

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NEW Stem Cells and Developmental Mechanisms
December 3-7, 2012
Suzhou, China

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