Volume 8.12 | Mar 31

Mammary Cell News 8.12 March 31, 2016
Mammary Cell News
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Hypoxia Induces the Breast Cancer Stem Cell Phenotype by HIF-Dependent and ALKBH5-Mediated m6A-Demethylation of NANOG mRNA
Researchers report that exposure of breast cancer cells to hypoxia stimulated hypoxia-inducible factor (HIF)-1α- and HIF-2α–dependent expression of AlkB homolog 5 (ALKBH5), an m6A demethylase, which demethylated NANOG mRNA, which encodes a pluripotency factor, at an m6A residue in the 3′-UTR. [Proc Natl Acad Sci USA] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)

AZD9496: An Oral Estrogen Receptor Inhibitor that Blocks the Growth of ER-positive and ESR1 Mutant Breast Tumors in Preclinical Models
Investigators report the identification and characterization of AZD9496, a non-steroidal small molecule inhibitor of estrogen receptor (ER) α which is a potent and selective antagonist and down-regulator of ERα in vitro and in vivo in ER-positive models of breast cancer. [Cancer Res] Full Article | Abstract

Early Adaptation and Acquired Resistance to CDK4/6 Inhibition in Estrogen Receptor-Positive Breast Cancer
Scientists report that estrogen receptor-positive breast cancer cells can adapt quickly to CDK4/6 inhibition and evade cytostasis, in part, via noncanonical cyclin D1-CDK2-mediated S-phase entry. [Cancer Res] Abstract

DS-8201a, a Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Anti-Tumor Efficacy with Differentiation from T-DM1
In vitro and in vivo pharmacological activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft models. The mechanism of action for the efficacy was also evaluated. [Clin Cancer Res] Abstract

Trop-2 Induces Tumor Growth through Akt and Determines Sensitivity to Akt Inhibitors
Trop-2 and Akt expression was shown to be tightly coordinated in human breast cancers, with virtual overlap with Akt activation profiles at T308 and S473, consistent with functional interaction in vivo. Akt allosteric inhibitors were shown to only block the growth of Trop-2-expressing tumor cells, both in vitro and in preclinical models, being ineffective on Trop-2-null cells. [Clin Cancer Res] Abstract

Targeting the Chromatin Remodeling Enzyme BRG1 Increases the Efficacy of Chemotherapy Drugs in Breast Cancer Cells
Researchers demonstrated that knockdown of brahma related gene product 1 (BRG1) sensitized triple negative breast cancer cells to chemotherapeutic drugs used to treat breast cancer. [Oncotarget] Full Article

Lysine Demethylase 2A Promotes Stemness and Angiogenesis of Breast Cancer by Upregulating Jagged1
The authors showed that expression of lysine demethylase 2A (KDM2A) is markedly increased in human breast cancer and its overexpression is associated with tumor progression and poor prognosis. Gene set enrichment analysis revealed that inhibition of KDM2A down-regulates angiogenic genes with concurrent reduction of Jagged1, NOTCH1 and HEY1 in the NOTCH signaling. [Oncotarget] Full Article

Silencing of Prrx1b Suppresses Cellular Proliferation, Migration, Invasion and Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer
Scientists found that paired-related homeobox 1b (Prrx1b) was significantly up-regulated in triple-negative breast cancer and associated with tumor size and vascular invasion of breast cancer. Silencing of Prrx1b suppressed the proliferation, migration and invasion of basal-like cancer cells. [J Cell Mol Med] Full Article


Efficacy and Safety of Leuprorelin Acetate 6-Month Depot, TAP-144-SR (6M), in Combination with Tamoxifen in Postoperative, Premenopausal Patients with Hormone Receptor-Positive Breast Cancer: A Phase III, Randomized, Open-Label, Parallel-Group Comparative Study
Researchers assessed the non-inferiority of the 6-month depot formulation, TAP-144-SR (6M) 22.5 mg to the 3-month depot formulation, TAP-144-SR (3M) 11.25 mg in postoperative, premenopausal patients with hormone receptor-positive breast cancer. [Breast Cancer] Full Article

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Translating Neoadjuvant Therapy into Survival Benefits: One Size Does Not Fit All
Substantial improvements in the pathological complete response rate to anti-HER2 therapy, a proposed surrogate end point for long-term clinical benefit, have been observed with neoadjuvant dual-agent HER2 blockade. Thus, it was hypothesized that this approach would provide additional survival benefits over standard-of-care therapy with the anti-HER2 antibody trastuzumab in the adjuvant setting. [Nat Rev Clin Oncol] Abstract

Treating Cancer with Selective CDK4/6 Inhibitors
Results of pivotal Phase III trials investigating palbociclib in patients with advanced-stage estrogen receptor-positive breast cancer have demonstrated a substantial improvement in progression-free survival, with a well-tolerated toxicity profile. [Nat Rev Clin Oncol] Abstract

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SRI Biosciences – Stanford Drug Discovery and Development Program to Explore New Molecular Target for Treatment of Triple Negative Breast Cancer
A new collaborative project between scientists at SRI International and physician-researchers from Stanford Cancer Institute will support development of novel drugs for treatment of triple-negative breast cancer. [SRI Biosciences] Press Release

Puma Biotechnology Updates Timeline for Filing New Drug Application
Puma Biotechnology, Inc. announced that based on its recent meetings with the U.S. Food and Drug Administration, the company now plans to submit its New Drug Application for the approval of neratinib for the treatment of extended adjuvant breast cancer that has previously been treated with a trastuzumab-containing regimen in mid-2016. [Puma Biotechnology, Inc.] Press Release

Southwest X-Ray LP Installs Gamma Medica’s LumaGEM® Molecular Breast Imaging System as a Secondary Screening and Diagnostic Tool for Women with Dense Breasts
Gamma Medica announced that Southwest X-Ray, the leading outpatient services provider in El Paso, has installed Gamma Medica’s LumaGEM® Molecular Breast Imaging system. [Gamma Medica] Press Release

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European Medicines Agency (European Union)

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Therapeutic Goods Administration (Australia)
NEW International Agency for Research on Cancer (IARC) 50th Anniversary Conference
July 7-10, 2016
Lyon, France

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NEW Faculty Position – Tumor Immunology (John Wayne Cancer Institute at Providence Saint John’s Health Center)

NEW Postdoctoral Fellow – Noncoding RNAs in Breast Cancer (University of Texas MD Anderson Cancer Center)

NEW Postdoctoral Fellow – Breast and Ovarian Cancer (Johns Hopkins University School of Medicine)

PhD Fellowship – Breast Cancer (INCLIVA Health Research Institute)

Postdoctoral Fellowship – Platelets in Metastatic Breast and Colon Cancer (Université de Strasbourg)

Research Associate – Breast Cancer and Huntington’s Disease (University of Pittsburgh Drug Discovery Institute)

Postdoctoral Fellowship – Tumor Biology of Breast and Lung Cancer (Cold Spring Harbor Laboratory)

Postdoctoral Fellowship – Microenvironment of Breast Cancer (Icahn School of Medicine)

Postdoctoral Fellowship – Breast and Prostate Cancer Molecular Mechanisms (Feinberg School of Medicine)

Postdoctoral Fellowship – Epigenetic Reprogramming of Breast Cancer Stem Cells (University of Toronto)

Postdoctoral Fellowship – Various Projects in Cancer Biology (National University of Singapore)

Postdoctoral Fellowship – Genetic and Epigenetic Variability in Breast Cancer (The University of Tennessee Health Science Center)

Pathologist – Breast/Gastrointestinal/Genitourinary Cancer (Beth Israel Deaconess Medical Center)

Manager – Medical and Breast Imaging (Fred Hutchinson Cancer Research Center)

Clinical Pathways Associate – Cancer Therapeutics (Fred Hutchinson Cancer Research Center)

Director Clinical Research – Medical Oncology (Fred Hutchinson Cancer Research Center)

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