Cancer Stem Cell News Volume 5.25 | Jun 29 2016

TOP STORY

Researchers Discover How Faulty Genetic Instructions Drive a Deadly Blood Cancer in Adults

Researchers reveal how a mutation in the gene DNMT3A, which has been found in approximately 20 to 30 percent of cases of acute myeloid leukemia, gives normal cells faulty genetic instructions that contribute to the development of cancerous cells. In particular, they found that this gene mutation removes a check or “brake” on activity of “stemness” genes – genes that tell cells to remain as undifferentiated stem cells. [Press release from University of North Carolina at Chapel Hill discussing online prepublication in Cancer Cell] Press Release | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Tumor-Initiating Cell-Specific miR-1246 and miR-1290 Expression Converge to Promote Non-Small Cell Lung Cancer Progression

Investigators identified the tumor-initiating cell (TIC)-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumor initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumor-initiating potential of TICs and their ability to metastasize. [Nat Commun] Full Article

p62/SQSTM1 Enhances Breast Cancer Stem-Like Properties by Stabilizing MYC MRNA

Aberrant p62 overexpression has been implicated in breast cancer development. Researchers found that p62 expression was elevated in breast cancer stem cells, including CD44⁺CD24⁻ fractions, mammospheres, ALDH1⁺ populations and side population cells. [Oncogene] Full Article

Differential Propagation of Stroma and Cancer Stem Cells Dictates Tumorigenesis and Multipotency

Scientists performed high-throughput marker expression analysis and investigated the tumorigenicity of glioblastoma multiforme cells enriched under different culture conditions. They identified a marker panel that distinguished tumorigenic sphere cultures from non-tumorigenic serum cultures. Contrary to previous work, they found that ‘mixed cell cultures’ grown in serum conditions are tumorigenic and express cancer stem cell markers. [Oncogene] Full Article

Bedaquiline, an FDA-Approved Antibiotic, Inhibits Mitochondrial Function and Potently Blocks the Proliferative Expansion of Stem-Like Cancer Cells (CSCs)

Researchers hypothesized that, in mammalian cells, bedaquiline might target the mitochondrial ATP-synthase, leading to mitochondrial dysfunction and ATP depletion. They showed that bedaquiline has anti-cancer activity, directed against CSCs. [Aging (Albany NY)] Full Article

Impact of the SCF Signaling Pathway on Leukemia Stem Cell-Mediated ATL Initiation and Progression in an HBZ Transgenic Mouse Model

Previously, the authors successfully identified an adult T-cell leukemia (ATL) stem cell (ATLSC) candidate as the c-kit⁺/CD38^–/CD71^– cells in an ATL mouse model using Tax transgenic mice. Here, with a new ATL mouse model using HBZ-transgenic mice, they further discovered that the functional ATLSC candidate, which commonly expresses c-kit, is drug-resistant and has the ability to initiate tumors and reconstitute lymphomatous cells. [Oncotarget] Full Article

Inhibition of the Glucocorticoid Receptor Results in an Enhanced miR-99a/100-Mediated Radiation Response in Stem-Like Cells from Human Prostate Cancers

Scientists have demonstrated that low expression of miR-99a and miR-100 is present in cell populations which are relatively radiation insensitive, for example in prostate cancer stem cells and in castration-resistant prostate cancer. [Oncotarget] Full Article

DDX3 Represses Stemness by Epigenetically Modulating Tumor-Suppressive miRNAs in Hepatocellular Carcinoma

Scientists demonstrated that reduced DDX3 expression was not only inversely associated with tumor grade, but also predicted poor prognosis of hepatocellular carcinoma (HCC) patients. Knockdown of DDX3 in HCC cell line HepG2 induced stemness gene signature followed by occurrence of self-renewal, chemoresistance, epithelial to mesenchymal transition, migration as well as cancer stem cells expansion, and most importantly, DDX3 knockdown promotes tumorigenesis. [Sci Rep] Full Article

3,6-Dihydroxyflavone Suppresses the Epithelial-Mesenchymal Transition in Breast Cancer Cells by Inhibiting the Notch Signaling Pathway

Investigators found that 3,6-DHF could effectively inhibit epithelial to mesenchymal transition in breast cancer cells in vitro and in vivo. 3,6-DHF effectively inhibits the formation and proliferation of breast cancer stem cells, and consequently reduces the tumor-initiating capacity of tumor cells in NOD/SCID mice. [Sci Rep] Full Article

Cancer Stem Cells (CSCs), Cervical CSCs and Targeted Therapies

The authors provide an update of knowledge on CSCs and cervical CSCs (CCSCs), review potential stem cell markers and functional assays for identifying CCSCs, and describe the potential of targeting CCSCs in the treatment of cervical carcinoma. [Oncotarget] Full Article

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

Boston Biomedical Announces First Orphan Drug Designation for Napabucasin in Gastric/GEJ Cancer

Boston Biomedical announced that its lead investigational compound, napabucasin, has been granted Orphan Drug Designation from the U.S. Food and Drug Administration in the treatment of gastric cancer, including gastroesophageal junction cancer. Napabucasin is an orally administered cancer stemness inhibitor designed to inhibit cancer stemness pathways by targeting STAT3, and is currently being investigated in a global Phase III clinical trial in combination with paclitaxel in patients with advanced gastric and gastroesophageal junction (GEJ) cancer. [Boston Biomedical] Press Release

Statement from FDA Commissioner Robert Califf, M.D. Announcing the Acting Director of the FDA Oncology Center of Excellence

The Food and Drug Administration (FDA) is honored to be an integral part of the Vice President’s National Cancer Moonshot Initiative, which calls on the agency to leverage the combined skills of regulatory scientists and reviewers with expertise in drugs, biologics and devices to create the Oncology Center of Excellence. [U.S. Food and Drug Administration] Press Release

Oncolytics Biotech Inc. Announces Phase II Study in Female Patients with Colorectal Cancer Metastatic to the Liver

Oncolytics Biotech Inc. announced that, following submission to the U.S. Food and Drug Administration for review, the Investigational New Drug Application containing the protocol titled ‘Phase II study of REOLYSIN^® in combination with FOLFOX6, bevacizumab and pembrolizumab in female patients with KRAS-mutant colorectal cancer metastatic to the liver’ is now active. [Oncolytics Biotech Inc.] Press Release

NEW 2016 National Cancer Research Institute (NCRI) Cancer Conference
November 6-9, 2016
Liverpool, United Kingdom

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

NEW Institute Associate Scientist III – Target Biology (MD Anderson Cancer Center)

NEW Postdoctoral Fellowship – Wnt Pathway in Sarcoma Pathogenesis (University of Miami Health System)

Research Associate – Stem Cell Biology of the Intestine (University of Cambridge)

Postdoctoral Scientist – Leukemic Stem Cells (University of Oxford)

Senior Cancer Analyst – 100,000 Genomes Project (Queen Mary University of London)

Postdoctoral Researcher – DNA Damage Signaling (University of Oxford)

Postdoctoral Fellow – Cancer Stem Cell Biology (Cleveland Clinic Lerner Research Institute)

Postdoctoral Fellow – Biology of Tumor Initiating Cells (German Cancer Research Center)

Assistant Professor – Molecular Pharmacology, Systems Biology, Cancer Therapeutics (German Cancer Research Center)

Senior Research Scientist – Drug Discovery in Cancer (Vertex Pharmaceuticals)

Team Leader – Immune-Oncology (Fondation Toulouse Cancer Sante)

Postdoctoral Fellow – Adaptive T-Cell Therapy for Cancer (Memorial Sloan Kettering Cancer Center)

Postdoctoral Fellow – Myeloid Cells in Cancer Patients (The Wistar Institute)

Faculty Position – Multidisciplinary Research Programs (St. Jude Children’s Research Hospital)

Postdoctoral Fellow – Genome and Epigenome of Pediatric Cancer (St. Jude Children’s Research Hospital)

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