Mammary Cell News Volume 8.49 | Dec 15 2016

TOP STORY

Mechanism of Early Dissemination and Metastasis in Her2⁺ Mammary Cancer

Investigators showed that, in early lesions in mice and before any apparent primary tumor masses are detected, there is a sub-population of Her2⁺p-p38^lop-Atf2^loTwist1^hiE-cad^lo early cancer cells that is invasive and can spread to target organs. [Nature] Abstract

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Early Dissemination Seeds Metastasis in Breast Cancer

By studying metastasis in a HER2-driven mouse breast cancer model, researchers showed that progesterone-induced signaling triggers migration of cancer cells from early lesions shortly after HER2 activation, but promotes proliferation in advanced primary tumor cells. [Nature] Abstract

Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic Analysis

Investigators revealed that mutations in the AR- and FOXA1-regulated networks, in which BRCA1 plays a key role, were associated with significantly higher sensitivity to anthracycline/taxane chemotherapy in the MDACC cohort and significantly better survival outcome in the TCGA triple negative breast cancer (TNBC) cohort. They directly linked BRCA deficiency with increased clonal mutation burden and significantly enhanced chemosensitivity in TNBC. [PLoS Med] Full Article | Press Release

Overcoming Tamoxifen Resistance of Human Breast Cancer by Targeted Gene Silencing Using Multifunctional pRNA Nanoparticles

Recent studies have revealed that estrogen receptor coactivator Mediator Subunit 1 (MED1) plays a critical role in tamoxifen resistance through cross-talk with HER2. The authors assembled a three-way junction pRNA-HER2apt-siMED1 nanoparticle to target HER2-overexpressing human breast cancer via a HER2 RNA aptamer to silence MED1 expression. [ACS Nano] Abstract | Press Release

Tracing the Origin of Disseminated Tumor Cells in Breast Cancer Using Single-Cell Sequencing

Scientists applied single-cell sequencing to identify and trace the origin of disseminated tumor cells (DTCs) in breast cancer. By comparing the cells’ DNA copy number aberration landscapes with those of the primary tumors and lymph node metastasis, they established that 53% of the single cells morphologically classified as tumor cells are DTCs disseminating from the observed tumor. [Genome Biol] Full Article | Press Release

A Phosphorylation–Deubiquitination Cascade Regulates the BRCA2–RAD51 Axis in Homologous Recombination

The authors reported that ubiquitination of RAD51 hinders RAD51–BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51–BRCA2 binding and RAD51 recruitment and thus is critical for proper homologous recombination. Overexpression of UCHL3 renders breast cancer cells resistant to radiation and chemotherapy, while depletion of UCHL3 sensitizes cells to these treatments. [Genes Dev] Abstract | Press Release

PIK3CA Mutations Enable Targeting of a Breast Tumor Dependency through mTOR-Mediated MCL-1 Translation

Using a pharmacological screening approach, scientists discovered that combined inhibition of B cell lymphoma–extra large (BCL-X_L) and the mammalian target of rapamycin (mTOR)/4E-BP axis results in selective and synergistic induction of apoptosis in cellular and animal models of PIK3CA mutant breast cancers, including triple-negative tumors. Mechanistically, inhibition of mTOR/4E-BP suppresses myeloid cell leukemia–1 (MCL-1) protein translation only in PIK3CA mutant tumors, creating a synthetic dependence on BCL-X_L. [Cancer] Abstract

MCL-1 Inhibition Provides a New Way to Suppress Breast Cancer Metastasis and Increase Sensitivity to Dasatinib

To examine whether targeting myeloid cell leukemia-1 (MCL-1) may provide an effective treatment for breast cancer, researchers constructed inducible models of BIMs2A expression in MDA-MB-468 and MDA-MB-231 cells. They provided evidence that MCL-1 drives breast cancer cell invasion. [Breast Cancer Res] Full Article

Lipid Osteoclastokines Regulate Breast Cancer Bone Metastasis

Scientists showed that osteoclasts reprogram their lipid secretion to support cancer cells. Metabolomic profiling revealed elevated pro-metastatic arachidonic acid but reduced anti-metastatic lysophosphatidylcholines. This shift in lipid osteoclastokines synergistically stimulated tumor cell proliferation, migration, survival, and expression of pro-metastatic genes. [Endocrinology] Abstract

miR-151-3p Targets TWIST1 to Repress Migration of Human Breast Cancer Cells

Investigators explored the potential role of miR-151 in TWIST1 expression and cancer properties in human breast cancer cells. Moreover, they found that ectopic expression of miR-151-3p by infection with adenoviruses expressing miR-151 significantly decreased TWIST1 expression, migration and invasion, but did not affect cell growth and tumorsphere formation of human breast cancer cells. [PLoS One] Full Article

Protein-Bound Polysaccharide from Corbicula fluminea Inhibits Cell Growth in MCF-7 and MDA-MB-231 Human Breast Cancer Cells

Researchers extended the understanding of the anticancer mechanism of C. fluminea protein-bound polysaccharide. In MCF-7, CFPS-1 produced a significant up-regulation of p53, p21, Bax and cleaved caspase-7 and down-regulation of Cdk4, cyclin D1, Bcl-2 and caspase-7. These effects resulted in cell cycle blockade at the S-phase and apoptosis induction. [PLoS One] Full Article

Cellular and Molecular Mechanism Underlying Alcohol-Induced Aggressiveness of Breast Cancer

The authors discuss how the interaction between oxidative stress and epidermal growth factor receptor/ErbB2 signaling contributes to the cellular and molecular events associated with breast cancer aggressiveness. They also discuss the potential therapeutic approaches for cancer patients who drink alcoholic beverages. [Pharmacol Res] Abstract | Graphical Abstract

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Novartis LEE011 plus Letrozole Analyses Show Superior PFS across Broad Spectrum of Patients in First-Line HR⁺/HER2^– Advanced Breast Cancer versus Letrozole

Novartis announced additional analyses from the Phase III MONALEESA-2 study that show LEE011 plus letrozole significantly prolonged progression-free survival (PFS) across pre-planned patient subgroups with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR⁺/HER2^–) advanced or metastatic breast cancer, including post-menopausal women diagnosed de novo, those with visceral liver and lung metastases, and those with bone-only disease. [Press release from Novartis discussing research presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio] Press Release

Innocrin Pharmaceuticals Presents Data from the Ongoing Phase II Trial of Seviteronel in Estrogen Receptor-Positive or Triple-Negative Breast Cancer

Innocrin Pharmaceuticals, Inc. announced clinical results from the ongoing CLARITY (CYP17 Lyase and Androgen Receptor Inhibitor Treatment with Seviteronel) study. [Press release from Innocrin Pharmaceuticals, Inc. (Business Wire, Inc.) discussing research presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio] Press Release

Interim Results from Phase Ib/II Study Evaluating the Combination of Merck’s KEYTRUDA^® and Eisai’s HALAVEN^® Injection in Metastatic Triple-Negative Breast Cancer Presented

Merck and Eisai Inc. announced new interim data investigating Merck’s anti-PD-1 therapy, KEYTRUDA^®, in combination with Eisai’s microtubule dynamics inhibitor, HALAVEN^®, in patients with metastatic triple-negative breast cancer. [Press release from Merck discussing research presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio] Press Release

Seattle Genetics Highlights Phase I Data for Novel Antibody-Drug Conjugate SGN-LIV1A in Patients with Metastatic Breast Cancer

Seattle Genetics, Inc. presented data from an ongoing Phase I clinical trial evaluating SGN-LIV1A for patients with metastatic breast cancer (MBC), with particular focus on triple-negative MBC. [Press release from Seattle Genetics, Inc. discussing research presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio] Press Release

Genomic Health Announces Results from Multiple Oncotype DX^® Studies, Reinforcing Its Impact in Delivering Precision Medicine to Breast Cancer Patients around the World

Genomic Health, Inc. announced results from multiple studies demonstrating the unparalleled value of the Oncotype DX^® test in individualizing breast cancer treatment decisions for patients with various stages of the disease. [Press release from Genomic Health, Inc. discussing research presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio] Press Release

Syros Pharmaceuticals Presents New Preclinical Data Demonstrating Significant Anti-Proliferative Effects of Its First-In-Class Selective RARα Agonist in Genomically Defined Subsets of Breast Cancer

Syros Pharmaceuticals announced the presentation of new data on SY-1425, its first-in-class selective retinoic acid receptor alpha (RARα) agonist, showing that SY-1425 inhibited tumor growth in multiple preclinical models of breast cancer driven by high levels of RARA gene expression. [Press release from Syros Pharmaceuticals discussing research presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio] Press Release

Clinical Utility of Biocept’s Liquid Biopsy Platform Demonstrated in Study Results Presented

Biocept, Inc. announced that clinical data featuring its Target Selector^™ Circulating Tumor Cell platform demonstrated high concordance to tissue biopsy for the detection of actionable biomarkers in patients with metastatic breast cancer. [Press release from Biocept, Inc. discussing research presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio] Press Release

MetaStat Presents Positive Data from Two Clinical Studies of MetaSite Breast^™

MetaStat, Inc. announced results from two clinical studies of its MetaSite Breast^™ test, demonstrating that the MetaSite Score was significantly associated with increased risk of distant metastasis in Hormone Receptor (HR-positive), HER2-negative Early Stage Breast Cancer. [Press release from MetaStat, Inc. (Business Wire, Inc.) discussing research presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio] Press Release

Three New Studies Presented Further Demonstrate Value of MammaPrint^® and BluePrint^® in Individualizing Treatment for Breast Cancer Patients

Agendia, Inc. highlighted new data on its gold-standard MammaPrint 70-Gene Breast Cancer Recurrence Assay and BluePrint 80-Gene Molecular Subtyping Assay, from three studies. [Press release from Agendia, Inc. discussing research presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio] Press Release

Natera Announces Participation in I-SPY 2 TRIAL for Breast Cancer

Natera, Inc. announced a collaboration with Dr. Laura van’t Veer and Dr. Laura Esserman of UCSF and QuantumLeap Healthcare Collaborative to participate in the I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2), a multi-center study evaluating the safety and efficacy of investigational therapies combined with neoadjuvant treatment in women with newly diagnosed, locally advanced breast cancer. [Natera, Inc.] Press Release

Cancer Research UK and Bicycle Therapeutics Collaborate to Trial New Therapy for Advanced Solid Tumors

Cancer Research UK, Cancer Research Technology, and Bicycle Therapeutics have announced an agreement to trial a first-in-class drug for cancers of high unmet need. Cancer Research UK’s Centre for Drug Development will sponsor and fund a Phase Ia and Phase Ib clinical trial for a drug called BT1718 in patients with advanced solid tumors. [Bicycle Therapeutics] Press Release

United Kingdom Gives Green Light for Mitochondrial Replacement Technique

Authorities in the United Kingdom have given the go-ahead for mitochondrial replacement therapy, a new type of assisted reproduction that could allow some families to avoid passing on genetic disease. The technique is controversial because it combines genetic material from three people: two eggs and one sperm. The decision has been widely anticipated. It comes after years of debate and a change in the country’s laws passed by Parliament in 2015. [ScienceInsider] Editorial

Canada’s Government Scientists Get Antimuzzling Clause in Contract

Scientists working for the Canadian government have successfully negotiated a clause in their new contract that guarantees their right to speak to the public and the media about science and their research, without needing approval from their managers. [ScienceInsider] Editorial

In Canada, Case Spurs Concern over Misconduct Secrecy

In early 2013, scientists working in a laboratory led by a prominent cancer researcher at the University of British Columbia (UBC) in Vancouver, Canada, were getting worried. They were unable to reproduce results from several of the researcher’s experiments, and suspected some of the original work was fraudulent. An investigation by UBC ultimately confirmed their fears: In 2014, investigators identified 29 instances of scholarly misconduct, 16 of them “serious,” including falsification and fabrication of data, according to university correspondence obtained by Retraction Watch. [ScienceInsider] Editorial

NEW AACR Annual Meeting 2017
April 1-5, 2017
Washington, D.C., United States

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

NEW Postdoctoral Fellow – Cancer Biology (University of Illinois at Chicago)

Two Postdoctoral Opportunities – Cancer Epigenetics (International Agency for Research on Cancer)

Postdoctoral Researcher – Nuclear Medicine Dosimetry (University of Oxford)

Postdoctoral Fellow – Breast Cancer Biology (Icahn School of Medicine at Mount Sinai)

Postdoctoral Position – Breast and Lung Cancer (Cold Spring Harbor Laboratory)

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Assistant Professor – Cancer Biology, Cancer Genomics and Precision Medicine (Wake Forest Baptist Comprehensive Cancer Center)

Research Fellow – Breast Cancer Research (Dana-Farber Cancer Institute)

Postdoctoral Fellow – Cancer Prevention Studies (American Cancer Society)

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