Mammary Cell News Volume 11.12 | Apr 4 2019

TOP STORY

Intraclonal Plasticity in Mammary Tumors Revealed through Large-Scale Single-Cell Resolution 3D Imaging

Imaging of multicolor lineage-tracing models of breast cancer targeted to either basal or luminal progenitor cells revealed profound clonal restriction during progression. Expression profiling of clones arising in Pten/Trp53-deficient tumors identified distinct molecular signatures. [Cancer Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Extracellular Vesicle-Packaged HIF-1α-Stabilizing lncRNA from Tumor-Associated Macrophages Regulates Aerobic Glycolysis of Breast Cancer Cells

HIF-1α-stabilizing long noncoding RNA (HISLA) blocked the interaction of PHD2 and HIF-1α to inhibit the hydroxylation and degradation of HIF-1α. Reciprocally, lactate released from glycolytic tumor cells upregulated HISLA in macrophages, constituting a feed-forward loop between tumor-associated macrophages and tumor cells. [Nat Cell Biol] Abstract

Temporal Dynamic Reorganization of 3D Chromatin Architecture in Hormone-Induced Breast Cancer and Endocrine Resistance

Researchers identified subsets of temporally highly dynamic compartments predominantly associated with active open chromatin and found that these highly dynamic compartments showed higher alteration in tamoxifen-resistant breast cancer cells. [Nat Commun] Full Article

Mad1 Destabilizes p53 by Preventing PML from Sequestering MDM2

Upregulated mitotic arrest deficient 1 (Mad1) localized to promyelocytic leukemia (PML) nuclear bodies in breast cancer and cultured cells. The C-terminus of Mad1 directly interacted with PML, and this interaction was enhanced by sumoylation. [Nat Commun] Full Article

Energetic Regulation of Coordinated Leader-Follower Dynamics during Collective Invasion of Breast Cancer Cells

Using a combination of in vitro spheroid and ex vivo organoid invasion models, scientists found that cancer cells dynamically rearranged leader and follower positions during collective invasion. [Proc Natl Acad Sci USA] Abstract

Epigenetic Regulation of NAMPT by NAMPT-AS Drives Metastatic Progression in Triple-Negative Breast Cancer

NAMPT-AS epigenetically regulated the expression of NAMPT in two divergent ways: NAMPT-AS recruited POU2F2 to activate the transcription of NAMPT, and NAMPT-AS acted as a competing endogenous RNA to rescue NAMPT degradation from miR-548b-3p. [Cancer Res] Abstract | Full Article

The KRAS-Variant and Its Impact on Normal Breast Epithelial Cell Biology

Investigators found that KRAS-variant normal breast epithelial cells exhibited a mesenchymal phenotype, which appeared to be due to numerous molecular changes, including miRNA dysregulation and autocrine pathway alterations, including elevated TGF-β, resulting in ZEB and SNAIL upregulation. [Cell Death Differ] Abstract

TRAIL Receptor Activation Overcomes Resistance to Trastuzumab in HER2 Positive Breast Cancer Cells

The authors used primary cell lines resistant to trastuzumab, as well as cells made secondarily resistant to the drug upon continuous exposure. Using genomic and proteomic approaches, a deregulation in cell death pathways was identified in trastuzumab-resistant cells. [Cancer Lett] Abstract

Cx43 Expression Correlates with Breast Cancer Metastasis in MDA-MB-231 Cells in Vitro, in a Mouse Xenograft Model and in Human Breast Cancer Tissues

Connexin43 (Cx43) over-expression increased protein levels of epithelial markers E-cadherin and zonula occludens 1 expression and resulted in the sequestration of β-catenin at the cell membrane, while Cx43 knock-down induced protein expression of the mesenchymal marker N-cadherin and increased the invasive potential of MDA-MB-231 cells down-regulating Cx43. [Cancers] Full Article

New Insights into Radioresistance in Breast Cancer Identify a Dual Function of miR-122 as a Tumor Suppressor and OncomiR

Differential expression profiling assays identified 16 deregulated miRNAs in acquired-radioresistant breast cancer cells, of which miR-122 was observed to be up-regulated. Functional analysis revealed that miR-122 had a role as a tumor suppressor in parental cells by decreasing survival and promoting radiosensitivity. [Mol Oncol] Abstract | Full Article

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Interaction of Host Immunity with HER2-Targeted Treatment and Tumor Heterogeneity in HER2-Positive Breast Cancer

The authors review the current pre-clinical and clinical data on the interplay between the immune system and HER2+ breast cancer, focusing on different HER2-targeted treatments and the biological heterogeneity that exists within HER2+ disease. [J Immunother Cancer] Full Article

Recent Advances in Understanding Tumor Stroma-Mediated Chemoresistance in Breast Cancer

The bi-directional interactions between tumor and stromal cells substantially affect tumor cell biology. Investigators discuss current available information on these interactions in breast cancer chemo-resistance. [Mol Cancer] Full Article

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

MacroGenics Reports Presentation of Data

Preclinical data presented showed that margetuximab, while retaining the same Fc-independent tumor growth-inhibition activity as trastuzumab, exhibited more potent antibody-dependent cell-mediated cytotoxicity and induced greater activation and proliferation of NK cells in vitro compared to trastuzumab. [Press release from MacroGenics, Inc. discussing research presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

BriaCell’s Lead Candidate Combined with KEYTRUDA^®: Strong Evidence of Rapid Additive or Synergistic Anti-Tumor Activity

BriaCell Therapeutics Corp. announced early efficacy data of BriaCell’s novel immunotherapy, Bria-IMT™, in combination with pembrolizumab in advanced breast cancer patients. [Press release from BriaCell Therapeutics Corp. discussing research presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

Roche’s Ipatasertib in Combination with Tecentriq and Chemotherapy Shows Promising Anti-Tumor Activity in Triple-Negative Breast Cancer in Early Phase Trial

Roche presented the initial results from a Phase Ib study evaluating the efficacy and safety for the combination of ipatasertib, Tecentriq^® and chemotherapy as a first-line treatment option for people with advanced triple-negative breast cancer. [Press release from Roche Group discussing research presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

Cyclacel Announces Presentation of Phase I Data of Sapacitabine Regimen in Patients with BRCA Mutant Breast Cancer

Cyclacel Pharmaceuticals, Inc. announced Phase I clinical data from the company’s DNA damage response program with an oral, sequential regimen of sapacitabine and seliciclib as a treatment in patients with BRCA mutant metastatic breast cancer. [Press release from Cyclacel Pharmaceuticals, Inc. discussing research presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

BriaCell Announces Clinical Trial Collaboration Agreement with Incyte

BriaCell Therapeutics Corp. announced a clinical trial collaboration and supply agreement with Incyte. The agreement is focused on, but not limited to, the selection of novel combinations for the treatment of advanced breast cancer along with a planned clinical study of BriaCell’s lead candidate, Bria-IMT™, with Incyte’s selected compounds for advanced breast cancer. [BriaCell Therapeutics Corp.] Press Release

Oncology Venture Obtains Option to In-License the European Rights to the FDA Approved Ixabepilone

Oncology Venture A/S announced that the company has obtained an exclusive option to in-license the European rights to ixabepilone from the pharmaceutical company R-Pharm US, LLC. [Oncology Venture A/S] Press Release

Hemispherx Announces the First Participant Received Initial Dosing in Breast Cancer Clinical Trial Using Hemispherx’ Ampligen and Pembrolizumab

Hemispherx announced active initiation of a clinical trial sponsored by Roswell Park Comprehensive Cancer Center evaluating Hemispherx’ experimental drug Ampligen^®, a dsRNA TLR3 agonist, in combination with Merck’s pembrolizumab, an anti-PD-1 check-point blockade therapy, in the treatment of metastatic triple-negative breast cancer. [Hemispherx Biopharma, Inc.] Press Release

Australia Budget Fails to Impress Scientists

Australians are just weeks from a national election and the government’s latest budget prioritizes tax cuts, roads and small businesses ahead of spending on science. Projects in nuclear medicine, environment protection and gender equality in science received modest investments. But there was no new money for research grants, and universities would be worse off under the proposal. [Nature News] Editorial

India’s Clinical-Trial Rules to Speed Up Drug Approvals

India has announced new rules for clinical trials that will speed up drug approvals and remove the requirement for large studies to test the efficacy of drugs that have already been approved in other nations. The country will also introduce regulations for universities undertaking research involving people. [Nature News] Editorial

Staff Scientists at the University of California Set to Form a First-of-Its-Kind Union

There are 5,000 of them within the University of California system, with titles like project scientist or professional researcher. They’re not on the tenure track, but they power one of the world’s most prolific research institutions. Now, organizers are in the final stages of setting up a first-of-its-kind union exclusively for academic researchers who are not faculty, postdocs, or graduate students. [STAT News] Editorial

NEW Society for Immunotherapy of Cancer (SITC) 2019
November 6-10, 2019
National Harbor, Maryland, United States

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

NEW Faculty Position – Breast and Ovarian Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellowship – Breast Cancer Research (Washington University School of Medicine)

Postdoctoral Position – Breast Cell Atlas (University of Cambridge)

Professor – Breast Cancer (University Hospitals Cleveland Medical Center)

Postdoctoral Researcher – BRCA1/2-Deficient Tumors (University of Oxford)

Postdoctoral Associate – Cancer Immunology (The Jackson Laboratory)

Scientific Review Officer – Breast Cancer (METAvivor)

Faculty Position – Breast Cancer Research (The Mayo Clinic)

Postdoctoral Fellow – Cancer Bioinformatics (BC Cancer Research Center, PHSA)

Postdoctoral Fellowship – Breast Cancer (Providence John Wayne Cancer Institute)

Postdoctoral Fellow – Breast Cancer Research (City of Hope)

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