Mammary Cell News Volume 7.15 | Apr 23 2015

Targeting Matriptase in Breast Cancer Abrogates Tumor Progression via Impairment of Stromal-Epithelial Growth Factor Signaling
Scientists demonstrated by genetic deletion and silencing that the proliferation impairment in matriptase-deficient breast cancer cells is caused by their inability to initiate activation of the c-Met signaling pathway in response to fibroblast-secreted pro-HGF. [Nat Commun] Abstract

Modelling Breast Cancer Requires Identification and Correction of a Critical Cell Lineage-Dependent Transduction Bias
Researchers present an analytical method for quantifying transductional differences between cell types and an optimized protocol for transducing unsorted primary human breast cells in context. [Nat Commun] Full Article

p63/MT1-MMP Axis Is Required for In Situ to Invasive Transition in Basal-Like Breast Cancer
The authors report that expression of membrane-type 1 (MT1)-matrix metalloproteinase (MMP) increased during breast cancer progression at the in situ to invasive breast carcinoma transition. MT1-MMP is required for basement membrane (BM) transmigration of MCF10DCIS.com breast adenocarcinoma cells and is overexpressed in cell clusters overlying focal BM disruptions and at the invasive tumor front. [Oncogene] Abstract

CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer
Researchers investigated the role of estrogen dependent chemokine expression and subsequent cancer growth in human tissues and experimental breast cancer models. Estrogen exposure and targeted therapies were assessed in immune competent PyMT murine breast cancer, orthotopic human breast cancers in nude mice, cell culture of cancer cells, and freshly isolated human macrophages. [Clin Cancer Res] Abstract | Full Article

The Proteomic Landscape of Triple-Negative Breast Cancer
To discover molecular features of triple-negative breast cancer, scientists performed quantitative proteomics analysis of twenty human-derived breast cell lines and four primary breast tumors to a depth of more than 12,000 distinct proteins. They used this data to identify breast cancer subtypes at the protein level and demonstrate the precise quantification of biomarkers, signaling proteins, and biological pathways by mass spectrometry. [Cell Rep] Full Article | Graphical Abstract | Press Release

Stearoyl-CoA Desaturase 1 and Paracrine Diffusible Signals Have a Major Role in the Promotion of Breast Cancer Cell Migration Induced by Cancer-Associated Fibroblasts
Fibroblast/breast cancer cell co-cultures were set up to investigate the influence of normal fibroblasts and cancer-associated fibroblasts on gene and protein expression of stearoyl-CoA desaturase 1, the main enzyme regulating membrane fluidity, as well as on the protein level and activity of its transcription factor, the sterol regulatory element-binding protein 1, in MCF-7 and MDA-MB-231 cells. [Br J Cancer] Full Article

Targeting Breast Cancer Stem Cells in Triple-Negative Breast Cancer Using a Combination of LBH589 and Salinomycin
Scientists investigated the efficacy of combining a histone deacetylase inhibitor and a breast cancer stem cells-targeting agent (salinomycin) as a novel combination therapy for triple-negative breast cancer. [Breast Cancer Res Treat] Abstract

miR-218 Targets Survivin and Regulates Resistance to Chemotherapeutics in Breast Cancer
MicroRNA (miRNA) profiling of two drug-resistant breast cancer cell models indicated that miR-218 was down-regulated in both MCF-7/A02 and CALDOX cells. Ectopic expression of miR-218 resensitized both drug-resistant cell lines to doxorubicin and taxol due to an increase in apoptosis. [Breast Cancer Res Treat] Abstract

Impact of Kinesin Eg5 Inhibition by 3,4-Dihydropyrimidin-2(1H)-One Derivatives on Various Breast Cancer Cell Features
Researchers identified five 3,4-dihydropyrimidin-2(1H)-one derivatives with pronounced inhibitory activity on Eg5 motor protein interfering with the proper mitotic spindle assembly during cell division. These compounds impair the correct conclusion of cell cycle of the breast cancer cells and showed to be selective for tumor cells. [BMC Cancer] Abstract | Full Article

CLINICAL RESEARCH

Pazopanib plus Weekly Paclitaxel versus Weekly Paclitaxel Alone for Platinum-Resistant or Platinum-Refractory Advanced Ovarian Cancer (MITO 11): A Randomized, Open-Label, Phase II Trial
Investigators assessed the effect of adding pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer. [Lancet Oncol] Abstract

Fulvestrant with or without Selumetinib, a MEK 1/2 Inhibitor, in Breast Cancer Progressing after Aromatase Inhibitor Therapy: A Multicenter Randomized Placebo-Controlled Double-Blind Phase II Trial, SAKK 21/08
Scientists assessed the efficacy and safety of fulvestrant with selumetinib, a MEK 1/2 inhibitor, in advanced stage breast cancer progressing after aromatase inhibitor. [Eur J Cancer] Abstract

Molecular Characterization and Targeted Therapeutic Approaches in Breast Cancer
The authors review the current state of novel biological markers for breast cancer, the evidence to demonstrate their clinical validity and utility, and the implication for therapeutic targeting. [Breast Cancer Res] Full Article

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Experimental Immune Therapy Tested in Preliminary Study of Women with Triple-Negative Breast Cancer
Early data in a preliminary human study show that an experimental immune system drug is generally safe and well tolerated in women with metastatic, triple-negative breast cancer, a persistently difficult form of the disease to treat. [Press release from Johns Hopkins Medicine discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

Olaparib and Investigational PI3K Inhibitor BKM120 Combination Active against Ovarian and Breast Cancer Subtypes
Combination treatment with the poly ADP-ribose polymerase inhibitor olaparib and the investigational phosphatidylinositol-3-kinase (PI3K) inhibitor BKM120 was safe and yielded evidence of clinical benefit for women with triple-negative breast cancer and for those with high-grade serous ovarian cancer, according to data from a Phase I clinical trial [Press release from the Dana-Farber Cancer Institute discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

Generex Announces Presentation of Data Correlating Immune Response with Reduction of Relapse in AE37 Phase II Breast Cancer Trial
Generex Biotechnology Corporation announced presentation of data from the on-going Phase II clinical trial of the AE37 breast cancer vaccine correlating local immune response to a reduction in relapse. [Press release from Generex Biotechnology Corporation discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

New PARP Inhibitor Combo Shows Early Promise for Cancer Patients with and without BRCA Mutations
A combination of two molecularly targeted drugs, olaparib and the investigational agent AZD5363, was safe and yielded responses in patients with a variety of cancer types, including breast, ovarian, and prostate cancers, regardless of BRCA1/2 mutation status, according to data from the ComPAKT Phase I clinical trial. [Press release from American Association for Cancer Research (AACR) discussing research presented at the 2015 AACR Annual Meeting, Philadelphia] Press Release

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University of Alberta Receives $1.6 Million for Breast Cancer Research
Six University of Alberta researchers have received $1.6 million in funding from the Canadian Breast Cancer Foundation. The research grants will help accelerate discovery of new and better ways to detect, treat and prevent breast cancer. [University of Alberta] Press Release

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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NEW PhD Student – Epigenetic Editing to Mimic and Reverse Breast Cancer Resistance (University Medical Center Groningen)

NEW PhD Student – Novel Molecular Biomarkers for Breast Cancer (University of Gothenburg)

PhD Student – Epigenetic Editing to Mimic and Reverse Breast Cancer Resistance (University Medical Center Groningen)

Postdoctoral Fellow – Extracellular Matrix Alterations Associated with Breast Cancer (Institute of Cancer Research)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Senior Cancer Bioinformatics Officer – Breast Cancer (Institute of Cancer Research)

Biostatistician – Molecular and Genetic Breast Cancer Epidemiology (Netherlands Cancer Institute)

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

Postdoctoral Fellow – Breast Cancer & Stem Cell Biology (University of Cincinnati)

Postdoctoral Fellow – Gene Regulation in Breast Cancer/Stem Cell Biology (University of Cincinnati College of Medicine)

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