Volume 10.25 | Jun 28

TOP STORY

Combination Therapy May Revive Prospects for ‘Embattled’ Breast Cancer Drugs

More than 60 percent of breast cancer cases involve defects in the same biochemical chain of events within cancer cells — known as the PI3 kinase pathway — but efforts to develop therapies targeting this pathway have met with little success after hundreds of mostly failed clinical trials. Now, using an innovative, unbiased laboratory method, University of California San Francisco scientists may have finally cracked the case. [Press release from the University of California San Francisco discussing online prepublication in Nature Chemical Biology] Press Release | Abstract

(Ranked by impact factor of the journal)

Loss of E-Cadherin Enhances IGF1-IGF1R Pathway Activation and Sensitizes Breast Cancers to Anti-IGF1R/InsR Inhibitors

Researchers demonstrated a direct endogenous interaction between insulin-like growth factor 1 receptor (IGF1R) and E-cadherin at points of cell-cell contact. Increased expression of IGF1 ligand and levels of IGF1R/insulin receptor (InsR) phosphorylation were observed in E-cadherin deficient estrogen receptor positive invasive lobular carcinoma compared to invasive ductal carcinoma tumors. [Clin Cancer Res] Abstract

Loss of Estrogen-Regulated MIR135A1 at 3p21.1 Promotes Tamoxifen Resistance in Breast Cancer

The authors showed that frequent deletion of the MIR135A1 locus was associated with poor prognosis in primary breast cancer. Forced expression of miR-135a decreased breast cancer progression, whilst inhibition of miR-135a with a specific miRNA sponge elicited opposing effects, suggestive of a tumor suppressive role of miR-135a in breast cancer. [Cancer Res] Abstract

FBXO22 Possesses Both Pro-Tumorigenic and Anti-Metastatic Roles in Breast Cancer Progression

Investigators reported that F-box only protein 22 (FBXO22) plays a dual role in mammary tumorigenesis and metastasis. FBXO22 was upregulated in primary breast tumors and promoted cell proliferation and colony formation in vitro and xenograft tumorigenicity in vivo. [Cancer Res] Abstract

Improved Efficacy of Mitochondrial Disrupting Agents upon Inhibition of Autophagy in a Mouse Model of BRCA1-Deficient Breast Cancer

Scientists found that Rb1cc1 deletion suppressed tumorigenesis in the BRCA1-deficient model when compared to wild type and heterozygous Rb1cc1 controls. Loss of RB1CC1 decreased mitochondrial mass and oxidative respiratory capacity of these tumor cells, along with a decrease in the phosphorylation of MTOR substrates and transcript levels of genes involved in mitochondrial biogenesis. [Autophagy] Abstract

High Expression of CD200 and CD200R1 Distinguishes Stem and Progenitor Cell Populations within Mammary Repopulating Units

Aiming to unravel the top of the mammary epithelial cell hierarchy, a subset of the CD49f^highCD24^med mammary repopulating units (MRUs) were identified by flow cytometry, expressing high levels of CD200 and its receptor CD200R1. These MRU^{CD200/CD200R1} repopulated a larger area of de-epithelized mammary fat pads than the rest of the MRUs, termed MRU^{not CD200/CD200R1}. [Stem Cell Reports] Full Article | Graphical Abstract

Enhanced PAPSS2/VCAN Sulfation Axis Is Essential for Snail-Mediated Breast Cancer Cell Migration and Metastasis

Snail induced the expression of PAPSS2, a gene that encodes a rate-limiting enzyme in sulfation pathway, and VCAN, a gene that encodes the chondroitin sulfate proteoglycan Versican in multiple breast cancer cells. Depletion of PAPSS2 in MCF7 and MDA-MB-231 cells resulted in reduced cell migration, while overexpression of PAPSS2 promoted cell migration. [Cell Death Differ] Abstract

Appraising the “Entourage Effect”: Antitumor Action of a Pure Cannabinoid versus a Botanical Drug Preparation in Preclinical Models of Breast Cancer

Researchers compared the antitumor efficacy of pure Δ⁹-tetrahydrocannabinol (THC) with that of a botanical drug preparation (BDP). The BDP was more potent than pure THC in producing antitumor responses in cell culture and animal models of ER⁺/PR⁺, HER2⁺ and triple-negative breast cancer. While pure THC acted by activating cannabinoid CB₂ receptors and generating reactive oxygen species, the BDP modulated different targets and mechanisms of action. [Biochem Pharmacol] Abstract | Graphical Abstract

ER-α36 Mediates Cisplatin Resistance in Breast Cancer Cells through EGFR/HER-2/ERK Signaling Pathway

ER-α36 was expressed at higher levels in cisplatin-resistant breast cancer cells compared to cisplatin sensitive cells. Cisplatin induced up-regulation of ER-α36 in a dose-dependent manner in breast cancer cells. The up-regulation of ER-α36 resulted in increased activation of nongenomic estrogen signaling, which was responsible for cisplatin resistance. [J Exp Clin Cancer Res] Full Article

Estrogen Promotes Progression of Hormone-Dependent Breast Cancer through CCL2-CCR2 Axis by Upregulation of Twist via PI3K/AKT/NF-κB Signaling

Chemokine (C-C motif) ligand 2 (CCL2) expression positively correlated with Twist staining and aggressiveness of breast cancer. Knockdown of Twist in MCF-7 cells significantly inhibited 17β-estradiol-induced CCL2 production, indicating an essential role of Twist in CCL2 regulation under estrogenic condition. [Sci Rep] Full Article

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CDK4/6 Inhibitors in Breast Cancer Therapy: Current Practice and Future Opportunities

Except for estrogen receptor positivity, no biomarkers predictive of response to CDK4/6 inhibitors have been identified to date. Based on mechanistic insights here described, CDK4/6 inhibitors are currently being explored in combination with other agents, including targeted therapies, immunotherapy and chemotherapy. [Pharmacol Ther] Abstract

Clinical and Molecular Aspects of Breast Cancer: Targets and Therapies

The authors analyze the current and potential molecular markers that can help to improve the strategies for breast cancer therapy. [Biomed Pharmacother] Abstract

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Arcus Biosciences and Infinity Pharmaceuticals Announce Clinical Collaboration to Evaluate Lead Programs in Triple-Combination Studies

The collaboration will evaluate IPI-549 in combination with AB928, Arcus’s dual adenosine receptor antagonist, and AB122, Arcus’s anti-PD-1 antibody, as well as IPI-549 in combination with AB928 and chemotherapy in patients with triple negative breast cancer or ovarian cancer in four separate cohorts. [Arcus Biosciences] Press Release

Puma Biotechnology Announces Results of CHMP Reexamination of MAA for Neratinib for Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer

Puma Biotechnology, Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive trend vote recommending the approval of the Marketing Authorisation Application (MAA) for neratinib for the extended adjuvant treatment of early stage HER2-positive hormone receptor positive breast cancer. [Puma Biotechnology, Inc.] Press Release

Pfizer Announces Overall Survival Results from Phase III PALOMA-3 Trial of IBRANCE^® (Palbociclib) in HR⁺, HER2^– Metastatic Breast Cancer

Pfizer announced overall survival results from the Phase III PALOMA-3 trial, which evaluated IBRANCE^® in combination with fulvestrant compared to placebo plus fulvestrant in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2^–) metastatic breast cancer whose disease has progressed after prior endocrine therapy. [Pfizer Inc.] Press Release

CytRx Corporation Highlights Aldoxorubicin Included in New NantCell Inc. Triple Negative Breast Cancer Clinical Trial

CytRx Corporation highlighted that aldoxorubicin licensee NantCell, Inc., has dosed the first patient in the Phase Ib portion of a Phase Ib/II clinical trial for patients with triple negative breast cancer. [CytRx Corporation] Press Release

Science Candidates: High-Tech Smarts Aren’t Enough for Defeated Obama Aide

For many first-time congressional candidates with science and technology backgrounds, fundraising can be a major obstacle. Not to Brian Forde, who was once a senior technology adviser to former-President Barack Obama. [ScienceInsider] Editorial

Firm That Tallies Controversial Journal Impact Scores Moves to Provide More Context

Stung by years of criticism that its journal impact factors have distorted scholarly publishing, the private firm Clarivate Analytics based in Philadelphia, Pennsylvania, rolled out an updated version of its Journal Citation Reports database that it says provides context useful to understanding journals’ characteristics and audiences. [ScienceInsider] Editorial

Macchiarini Guilty of Misconduct, but Whistleblowers Share Blame, New Karolinska Institute Verdict Finds

The Karolinska Institute in Stockholm has finally, officially, found disgraced surgeon Paolo Macchiarini guilty of scientific misconduct. However, the verdict is a bitter pill for the four people who raised the alarm about Macchiarini’s fraud. [ScienceInsider] Editorial

Top US Court Upholds Trump Travel Ban: Student Visas Already in Decline

he travel restrictions now vary by country, and include some exemptions for students. But data from the Department of Justice reveal that the government issued just 289 visas to students from Iran, Libya, Yemen and Somalia in the first three months of this year. [Nature News] Editorial

NEW 2018 Till & McCulloch Meetings (TMM2018)
November 12-14, 2018
Ottawa, Ontario, Canada

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

NEW Clinical Research Scientist – Oncology Medical Affairs Breast Cancer (Lilly)

NEW Instructor or Assistant Professor – Breast and Colon Cancer Metastasis Research (Louisiana State University Health Sciences Center)

Cancer Faculty Investigators – Basic & Translational Cancer Research (The University of Alabama)

Postdoctoral Fellow – Molecular Mechanisms of Breast & Colon Cancers (Dalhousie University)

Post-doctoral Fellow – Ovarian and Breast Cancers (John Hopkins University)

Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University Feinberg School of Medicine)

Postdoctoral Research Associate – Breast Cancer (Howard University)

Postdoctoral Fellow – Breast & Ovarian Cancer Genomics (University of Texas Health Science Center at Houston)

Cancer Scientists – Breast Cancer Research (Qatar Biomedical Research Institute)

Postdoctoral Position – Ovarian and Breast Cancer Research (Indiana University School of Medicine)

Postdoctoral Position – Breast Cancer Research (Northwestern University)

Postdoctoral Posion – Basic & Translational Breast Cancer Research (Northwestern University)

Postdoctoral Research Fellow – Translational Mitochondrial Research (Fred Hutch Cancer Research Center)

Postdoctoral Fellowship – Cancer Research (Mass General Hospital/Harvard Medical School)

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