Mammary Cell News Volume 7.21 | Jun 4 2015

Oncogenic PI3K and K-Ras Stimulate De Novo Lipid Synthesis through mTORC1 and SREBP
Oncogenic stimulation of mechanistic target of rapamycin complex 1 (mTORC1) signaling in an isogenic setting or a panel of eight breast cancer cell lines led to activation of the sterol regulatory element-binding proteins (SREBP1 and SREBP2) that are required for oncogene-induced lipid synthesis. The SREBPs are also required for the growth factor-independent growth and proliferation of oncogene-expressing cells. [Oncogene] Abstract

Induction of miRNA-181a by Genotoxic Treatments Promotes Chemotherapeutic Resistance and Metastasis in Breast Cancer
The authors showed that genotoxic treatments significantly increased the expression of miR-181a in triple negative breast cancer (TNBC) cells, which enhanced TNBC cell survival and metastasis upon doxorubicin treatment. [Oncogene] Abstract

MERIT40 Is an Akt Substrate that Promotes Resolution of DNA Damage Induced by Chemotherapy
Scientists identified a mechanism by which the PI3K/Akt pathway mediates resistance to doxorubicin. In addition to inducing DNA damage, doxorubicin triggers sustained activation of Akt signaling in breast cancer cells. [Cell Rep] Full Article | Graphical Abstract

Histone Deacetylase Inhibitor Entinostat Inhibits Tumor-Initiating Cells in Triple Negative Breast Cancer Cells
Investigators showed that entinostat (ENT) treatment can reduce the percentage of tumor-initiating cells (TICs) from triple negative breast cancer cells. ENT treatment was able to reduce the CD44^high/CD24^low cell population, ALDH-1 activity as well as protein and mRNA expression of known TIC markers such as Bmi-1, Nanog and Oct-4. [Mol Cancer Ther] Abstract

CD24⁺ Cells Fuel Rapid Tumor Growth and Display High Metastatic Capacity
Researchers demonstrated that CD24⁺ cells create intra-tumor heterogeneity, and display highly metastatic properties. The cells formed mammospheres in high efficiency and CD24⁺ tumors displayed rapid growth in both WT and MKR mice, and were more metastatic than CD24⁻ cells. [Breast Cancer Res]
Abstract | Full Article

Ubiquitin Specific Protease 2 Acts as a Key Modulator for the Regulation of Cell Cycle by Adiponectin and Leptin in Cancer Cells
Scientists investigated the effects of adiponectin and leptin on ubiquitin specific protease-2 (USP-2) expression and its potential role in the modulation of cell cycle. Treatment with globular adiponectin decreased, whereas leptin increased USP-2 expression both in human hepatoma and breast cancer cells. [Mol Cell Endocrinol] Abstract

Down-Regulation of Programmed Cell Death 4 (PDCD4) Is Associated with Aromatase Inhibitor Resistance and a Poor Prognosis in Estrogen Receptor-Positive Breast Cancer
Researchers determined PDCD4 expression levels in aromatase inhibitor (AI)-resistant breast cancer cell lines and estrogen receptor-positive breast cancer tumors and investigated the regulation of PDCD4 in AI-resistant breast cancer cell lines. [Breast Cancer Res Treat] Abstract

p53 Modulates Notch Signaling in MCF-7 Breast Cancer Cells by Associating with the Notch Transcriptional Complex via MAML1
The authors studied the regulation of Notch signaling by p53 in MCF-7 cells and normal human mammary epithelial cells. [J Cell Physiol] Abstract

AP4 Activates Cell Migration and EMT Mediated by p53 in MDA-MB-231 Breast Carcinoma Cells
It has been found that activating enhancer-binding protein (AP4) upregulates the genes involved in EMT and cell proliferation in colorectal cancer cells and that the aggressive human breast cancer cells MDA-MB-231 are highly metastatic. Therefore, investigators tested the hypothesis that AP4 may also affect cell migration and EMT in this cell type. [Mol Cell Biochem] Abstract

CLINICAL RESEARCH

Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer
This Phase III study involved 521 patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that had relapsed or progressed during prior endocrine therapy. Investigators randomly assigned patients in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant. [N Engl J Med] Full Article | Press Release

Adjuvant Denosumab in Breast Cancer (ABCSG-18): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
In this double-blind, placebo-controlled, Phase III trial, postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were randomly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every six months in 58 trial centres in Austria and Sweden. [Lancet] Abstract | Press Release

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Puma Biotechnology Announces Phase III Trial of PB272 in Extended Adjuvant Breast Cancer (ExteNET Trial) Demonstrates Statistically Significant Improvement in Disease Free Survival
Puma Biotechnology, Inc. announced the presentation of positive results from the Phase III clinical trial of Puma’s investigational drug PB272 (neratinib) for the extended adjuvant treatment of breast cancer. [Press release from Puma Biotechnology, Inc. discussing research presented at the 2015 American Society of Clinical Oncology (ASCO), Chicago] Press Release | Abstract

Oncothyreon Announces Presentation of Positive ONT-380 Data in HER2-Positive Breast Cancer and Updates Development Plan
Oncothyreon Inc. announced the presentation of positive data from the company’s ongoing trials of ONT-380, an orally active, reversible and selective small-molecule HER2 inhibitor for the treatment of breast cancer. [Press release from Oncothyreon Inc. discussing research presented at the 2015 American Society of Clinical Oncology (ASCO), Chicago] Press Release | Abstract

Anastrozole Prevents Recurrence More than Tamoxifen in Some with Noninvasive Breast Cancer
Anastrozole provides a significant benefit compared with tamoxifen in preventing recurrence after a lumpectomy and radiation therapy in postmenopausal women ages 60 years or younger who had ductal carcinoma in situ, a common diagnosis of non-invasive breast cancer. In women over age 60, it works as well as tamoxifen. [Press release from Loyola University Health System discussing research presented at the 2015 American Society of Clinical Oncology (ASCO), Chicago] Press Release | Abstract

Pfizer Announces Palbociclib More than Doubled Progression-Free Survival in Phase III Trial for Patients with HR⁺, HER2⁻ Metastatic Breast Cancer Whose Disease Has Progressed Following Endocrine Therapy
Pfizer Inc. announced study results demonstrating palbociclib in combination with fulvestrant was superior to treatment with a standard of care, fulvestrant, by significantly extending progression-free survival in women with hormone receptor-positive (HR⁺), human epidermal growth factor receptor 2-negative (HER2⁻) metastatic breast cancer whose disease has progressed during or after endocrine therapy. [Press release from Pfizer Inc. discussing research presented at the 2015 American Society of Clinical Oncology (ASCO), Chicago] Press Release | Abstract

MacroGenics Presents Updated Data from Phase I Study of Margetuximab
MacroGenics, Inc. announced that updated results of the Phase I study of margetuximab were reported. [Press release from MacroGenics, Inc. discussing research presented at the 2015 American Society of Clinical Oncology (ASCO), Chicago] Press Release | Abstract

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TESARO and Merck to Collaborate on a Combination Study of Niraparib and KEYTRUDA^® (Pembrolizumab)
TESARO, Inc. and Merck announced a collaboration to evaluate the combination of TESARO’s niraparib plus Merck’s anti-PD1 therapy, KEYTRUDA^® (pembrolizumab), in a Phase I/II clinical trial. [TESARO, Inc.] Press Release

ASCO Launches First-Ever Clinical Trial: Aims to Learn from Patients with Advanced Cancer Who Lack Standard Treatment Options
American Society of Clinical Oncology (ASCO) has announced its first-ever clinical trial that will offer patients with advanced cancer access to molecularly-targeted cancer drugs and collect “real-world” data on clinical outcomes to help learn the best uses of these drugs outside of indications approved by the Food and Drug Administration. [American Society of Clinical Oncology] Press Release

Innovative Health Research at Otago Receives Major Funding
University of Otago researchers have been awarded more than $30 million in new health research funding from the Health Research Council of New Zealand. The first project involves investigating the signaling pathways relating to Trib1, a protein that is often over-expressed in breast cancer. [University of Otago] Press Release

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Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Assistant/Associate/Full Professor – Oncology (Shanghai Jiao Tong University School of Medicine)

Postdoctoral Research Assistant – Role of BRCA1 in the Repair of DNA Damage (University of Dundee)

Postdoctoral Position – Malignant Breast Cancer Cells in the Bone Marrow Microenvironment (Duke University)

Postdoctoral Position – Fatty Acid Metabolism Inhibition on Chemoresistant TNBC Models (University of Girona)

Postdoctoral Fellow – Regulation of Growth and Survival of Breast Cancer Cells (Icahn School of Medicine at Mount Sinai)

Postdoctoral Technician – Prostate/Breast Cancer (Baylor College of Medicine)

Postdoctoral Research Fellow/Instructor – Prostate/Breast Cancer (Baylor College of Medicine)

Postdoctoral Positions – Molecular Cancer Biology (University of Pennsylvania)

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