Mammary Cell News Volume 9.03 | Jan 26 2017

TOP STORY

Breast Cancer Drugs Stop Working When Tumors ‘Make Their Own Fuel’

Scientists have discovered why a type of breast cancer drug stops working in some patients. They discovered that in one in four patients taking aromatase inhibitors, the tumors had increased production of aromatase in the cancer cells. The tumors appear to do this by increasing the number of aromatase genes, in a process called amplification. This allowed the cancer cells to effectively make their own estrogen, without relying on external sources of the hormone. [Press release from Imperial College London discussing online prepublication in Nature Genetics] Press Release | Abstract

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Constitutive NOTCH3 Signaling Promotes the Growth of Basal Breast Cancers

Using a novel antibody to detect active NOTCH3, investigators report that NOTCH3 signals constitutively in a panel of basal breast cancer cell lines and in more than one-third of basal tumors. Transcriptomic analyses generated a Notch gene signature that included Notch pathway components, the oncogene c-Myc, and the mammary stem cell regulator Id4. [Cancer Res] Abstract

FOXM1 Recruits Nuclear Aurora Kinase A to Participate in a Positive Feedback Loop Essential for the Self-Renewal of Breast Cancer Stem Cells

The authors report that nuclear Aurora kinase A (AURKA) can be recruited by Forkhead box subclass M1 (FOXM1) as a co-factor to transactivate FOXM1 target genes in a kinase-independent manner. They showed that AURKA and FOXM1 participate in a tightly coupled positive feedback loop to enhance breast cancer stem cells phenotype. [Oncogene] Full Article

The SigmaR1 Chaperone Drives Breast and Colorectal Cancer Cell Migration by Tuning SK3-Dependent Ca²⁺ Homeostasis

Scientists report that SigmaR1, a stress-activated chaperone, was required to increase calcium influx by triggering the coupling between SK3, a Ca²⁺-activated K⁺ channel and the voltage-independent calcium channel Orai1. They showed that SigmaR1 physically binds SK3 in breast cancer cells. [Oncogene] Abstract

An Essential Role of CBL and CBL-B Ubiquitin Ligases in Mammary Stem Cell Maintenance

The authors used the MMTV-Cre-mediated Cbl gene deletion on a Cbl-b-null background as well as a tamoxifen-inducible mammary stem cell (MaSC)-specific Cbl/Cbl-b double knockout, using Lgr5-GFP-CreERT, to demonstrate a mammary epithelial cell-autonomous requirement of CBL and CBL-B in the maintenance of MaSCs. [Development] Abstract

Highly Potent Non-Carboxylic Acid Autotaxin Inhibitors Reduce Melanoma Metastasis and Chemotherapeutic Resistance of Breast Cancer Stem Cells

Researchers report on inhibitors of autotaxin (ATX) derived by lead optimization of the benzene-sulfonamide in silico hit compound 3. The new analogues provide a comprehensive SAR of the benzene-sulfonamide scaffold that yielded a series of highly potent ATX inhibitors. In particular, compound 3b potently reduced in vitro chemotherapeutic resistance of 4T1 breast cancer stem-like cells to paclitaxel and reduced significantly B16 melanoma metastasis in vivo. [J Med Chem] Abstract

H19/let-7/LIN28 Reciprocal Negative Regulatory Circuit Promotes Breast Cancer Stem Cell Maintenance

Investigators showed that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Mechanistically, they found that H19 functions as a competing endogenous RNA to sponge miRNA let-7, leading to an increase in expression of a let-7 target, the core pluripotency factor LIN28, which is enriched in BCSC populations and breast patient samples. [Cell Death Dis] Full Article

The Role of miR-26a and miR-30b in HER2⁺ Breast Cancer Trastuzumab Resistance and Regulation of the CCNE2 Gene

Cell viability was evaluated in trastuzumab treated HER2⁺ BT474 wt, BT474r, HCC1954, and MDA-MB-231 cell lines, and the expression of miR-26a, miR-30b, and their target genes was measured. BT474 wt cell viability decreased by 60% and miR-26a and miR-30b were significantly overexpressed after trastuzumab treatment, but no differences were observed in resistant and control cell lines. [Sci Rep] Full Article

Cancer-Associated Fibroblasts Release Exosomal MicroRNAs that Dictate an Aggressive Phenotype in Breast Cancer

Differential expression profile analysis identified three microRNAs (miRs) increased in exosomes from cancer-associated fibroblasts (CAFs) as compared from normal fibroblasts. Breast cancer cells exposed to CAF exosomes or transfected with miRs exhibited a significant increased capacity to form mammospheres, increased stem cell and epithelial-mesenchymal transition markers, and anchorage-independent cell growth. [Oncotarget] Full Article

CLINICAL RESEARCH

First-In-Human Phase I Study of Margetuximab (MGAH22), an Fc-Modified Chimeric Monoclonal Antibody, in Patients with HER2-Positive Advanced Solid Tumors

Patients with HER2-positive breast or gastric cancer, or other carcinomas that overexpress HER2, for whom no standard therapy was available, were treated with margetuximab by intravenous infusion. Tumor reductions were observed in over half of response-evaluable patients with breast cancer including durable responders [Ann Oncol] Abstract

Topical Imiquimod plus Nab-Paclitaxel for Breast Cancer Cutaneous Metastases: A Phase II Clinical Trial

The authors sought to evaluate the safety and objective response rate of imiquimod in combination with systemic albumin bound paclitaxel in treatment-refractory breast cancer of the chest wall. Chemoimmunomodulation with a TLR-7 agonist and albumin bound paclitaxel was effective in inducing disease regression in treatment-refractory breast cancer chest wall metastases but responses were short-lived. [JAMA Oncol] Full Article

The Role of MDM2 and MDM4 in Breast Cancer Development and Prevention

Inherent defense against carcinogens depends on the individual molecular make-up of each person. Important molecular determinants of these responses are under the control of the mouse double minute (MDM) family: comprised of the proteins MDM2 and MDM4. Researchers focus on recent findings pertaining to the role of the MDM family in normal and malignant breast cells. [J Mol Cell Biol] Abstract

Patient-Derived Xenograft (PDX) Models in Basic and Translational Breast Cancer Research

The authors summarize current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward “credentialing” of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. [Cancer Metastasis Rev] Abstract

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

Cynvenio and Milenia Labs Enter into Exclusive Distribution Agreement for ClearID Breast Cancer Testing in Mexico

Cynvenio Biosystems, Inc. and Milenia Labs announced a distribution agreement for Cynvenio’s ClearID^® Breast Cancer, the first blood test for treatment selection and monitoring of patients with advanced breast cancer. [Cynvenio Biosystems, Inc.] Press Release

FDA Approves Fujifilm’s Digital Breast Tomosynthesis Option for Aspire Cristalle Digital Mammography System

FUJIFILM Medical Systems U.S.A., Inc. announced that its Digital Breast Tomosynthesis, as an optional software upgrade for its ASPIRE Cristalle digital mammography system, has received premarket approval from the U.S. Food and Drug Administration (FDA). [FUJIFILM Medical Systems U.S.A., Inc.] Press Release

World’s Foremost Institute on Death and Disease Metrics Gets Massive Cash Boost

The world’s premier centre for health metrics — the science of measuring and analysing global health problems, and how they relate to healthcare and biomedical research funding — will receive a US$279-million cash injection from the Bill & Melinda Gates Foundation. The cash will go towards expanding the institute’s work over the next decade and consolidating its primacy in the field. It is considered by far the biggest and most influential research centre for health metrics, and its work informs the funding and policy decisions of many national governments and local, regional and global organizations, including the World Bank and the US National Institutes of Health. [Nature News] Editorial

Candidates from Ethiopia, United Kingdom, and Pakistan Will Compete for WHO’s Top Slot

The World Health Organization (WHO) announced who will be up for election to the post of director-general in May. They are: former Ethiopian health minister and minister of foreign affairs Tedros Adhanom Ghebreyesus; British physician and United Nations official David Nabarro; and Pakistani cardiologist and former science minister Sania Nishtar. [ScienceInsider] Editorial

NEW 11^th European Breast Cancer Conference
March 21-23, 2017
Barcelona, Spain

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

NEW Postdoctoral Fellow – Breast Cancer Research (Gundersen Health System)

NEW Postdoctoral Researcher – Breast Cancer Epidemiology (Karolinska Institutet)

Research Scientist – Oncology Research (MedImmune)

Postdoctoral Associate – Department of Therapeutic Radiology (Yale University School of Medicine)

Postdoc Positions – Molecular Cancer Biology and Bioinformatics (University of Pittsburgh)

Postdoc Position – Mammary Epithelium and Breast Cancer (Helmholtz Association)

Postdoctoral Fellow – Breast Cancer (University of Hawaii Cancer Center)

Postdoctoral Fellow – Cancer Biology (University of Illinois)

Postdoctoral Associate – Mammary Stem Cell and Cancer Biology (University of Miami)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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