Cancer Stem Cell News Volume 5.15 | Apr 20 2016

Gastric Lgr5⁺ Stem Cells Are the Cellular Origin of Invasive Intestinal-Type Gastric Cancer in Mice
Researchers deleted Smad4 and PTEN in murine gastric lucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5⁺) stem cells by the inducible Cre-LoxP system and marked mutant Lgr5⁺ stem cells and their progeny with Cre-reporter Rosa26^tdTomato. Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer were found in the gastric antrum with the loss of Smad4 and PTEN. [Cell Res] Full Article

A Long Non-Coding RNA Targets microRNA miR-34a to Regulate Colon Cancer Stem Cell Asymmetric Division
Researchers report a novel long non-coding RNAs (lncRNAs), Lnc34a that is enriched in colon cancer stem cells and initiates asymmetric division by directly targeting the microRNA miR-34a to cause its spatial imbalance. [eLife] Abstract | Full Article Download

Use of a MCL-1 Inhibitor Alone to De-Bulk Melanoma and in Combination to Kill Melanoma Initiating Cells
Researchers examined the effects of the MCL-1 (BCL-2 family anti-apoptotic protein) inhibitor SC-2001 in killing non melanoma-initiating-cells, and melanoma-initiating-cells (MICs). Even at high doses, SC-2001 does not effectively eliminate MICs. In contrast, the combination of SC-2001 with ABT-737 (a BCL-2/BCL-XL/BCL-W inhibitor) significantly decreases ALDH⁺ cells, disrupts primary spheres, and inhibits the self-renewability of MICs. [Oncotarget] Full Article

Optimized Dissociation Protocol for Isolating Human Glioma Stem Cells from Tumorspheres via Fluorescence-Activated Cell Sorting
Five commonly used digestion reagents, Liberase-TL, trypsin, TrypLE, Accutase, and non-enzymatic cell dissociation solution, were used to dissociate glioma tumorspheres derived from two primary glioma specimens and the cell lines U87 and T98G. The dissociation time, cell viability, retention of CD133, and stemness capacity were assessed. [Cancer Lett] Abstract

Twist-Mediated Epithelial-Mesenchymal Transition Promotes Breast Tumor Cell Invasion via Inhibition of Hippo Pathway
Investigators report that Twist overexpression increased expression of PAR1, an upstream regulator of the Hippo pathway; PAR1 promotes invasion, migration, and cancer stem cell-like properties in breast cancer by activating the transcriptional co-activator TAZ. [Sci Rep] Full Article

Parthenolide and DMAPT Exert Cytotoxic Effects on Breast Cancer Stem-Like Cells by Inducing Oxidative Stress, Mitochondrial Dysfunction and Necrosis
Researchers report the production of mammospheres from three lines of triple-negative breast cancers cells and demonstrate that both parthenolide and its soluble analog dimethylaminoparthenolide (DMAPT) suppressed this production and induced cytotoxic effects in breast cancer stem-like cells, derived from dissociation of mammospheres. [Cell Death Dis] Full Article

The Influence of miR-34a Expression on Stemness and Cytotoxic Susceptibility of Breast Cancer Stem Cells
Scientists showed that miR-34a, as a tumor suppressor, could separately reduce the stemness of breast cancer stem cells (BCSCs) and activate the cytotoxic susceptibility of BCSCs to natural killer cells in vitro via down regulating the expression of Notch1 signaling molecules. [Cancer Biol Ther] Abstract

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MEI Pharma Announces New Clinical Data from First-in-Human Study of ME-401, A Next Generation Oral PI3K Delta Inhibitor
MEI Pharma, Inc. announced new clinical data from a first-in-human study of MEI Pharma’s investigational drug candidate, ME-401, a next generation oral PI3K delta inhibitor. The data suggest that ME-401 has an excellent pharmacokinetic and pharmacodynamic profile and the potential for an improved therapeutic window compared to other PI3K delta inhibitors. [Press release from MEI Pharma, Inc. discussing research presented at the American Association for Cancer Research (AACR) 2016 Annual Meeting, New Orleans] Press Release

Preclinical Data Presented At AACR Indicate Pacritinib’s Potential To Eradicate Therapy-Resistant Leukemia Stem Cells Residing In Bone Marrow Microenvironment
CTI BioPharma Corp. announced findings from an investigator-sponsored preclinical study indicating that pacritinib, an inhibitor of JAK2, FLT3, IRAK1 and CSF1R, may be effective in reducing survival of myelofibrosis and acute myeloid leukemia repopulating cells. Further, this study also demonstrated that the combination of pacritinib at low nanomolar concentrations with dasatinib may eliminate self-renewing leukemia stem cells in blast crisis of chronic myeloid leukemia with minimal toxicity toward normal progenitors. [Press release from CTI BioPharma Corp. discussing research presented at the American Association for Cancer Research (AACR) 2016 Annual Meeting, New Orleans] Press Release

DelMar Pharmaceuticals Updates Ongoing Phase I/II Refractory GBM Clinical Trial with VAL-083
DelMar Pharmaceuticals, Inc. presented updated data from an ongoing Phase I/II clinical trial in refractory glioblastoma multiforme with its lead anti-cancer product candidate, VAL-083 (dianhydrogalactitol). [Press release from DelMar Pharmaceuticals, Inc. discussing research presented at the American Association for Cancer Research (AACR) 2016 Annual Meeting, New Orleans] Press Release

Tocagen Presents Positive Preclinical, Proof-of-Mechanism Data
Tocagen Inc. announced positive preclinical, proof-of-mechanism data involving Toca 511 and 5-fluorocytosine were presented. The data demonstrate the potential for this investigational therapy to be used in combination with checkpoint inhibitors, specifically anti-PD-1 or anti-CTLA-4 antibodies, and as a potential treatment for metastatic colorectal cancer. [Press release from Tocagen Inc. discussing research presented at the American Association for Cancer Research (AACR) 2016 Annual Meeting, New Orleans] Press Release

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Onkos Surgical Enters Into Partnership with Vivex Biomedical, Inc.
Onkos Surgical and Vivex Biomedical, Inc. have come together to provide a portfolio of tissue products to support the needs of musculoskeletal oncologists and their patients. [Onkos Surgical] Press Release

Diplomat to Dispense VENCLEXTA™ for the Treatment of Chronic Lymphocytic Leukemia
Diplomat Pharmacy, Inc. announced that it is now filling prescriptions for VENCLEXTA™ (venetoclax). VENCLEXTA™ was recently approved by the U.S. Food and Drug Administration for the treatment of people with chronic lymphocytic leukemia who have received at least one prior therapy, including those with 17p deletion. [Diplomat Pharmacy, Inc.] Press Release

FDA Grants Orphan Drug Exclusivity to EVOMELA™ (Melphalan) for Injection, Indicated for Multiple Myeloma
Spectrum Pharmaceuticals announced that the U.S. Food and Drug Administration Office of Orphan Products Development has granted seven years of orphan drug exclusivity for EVOMELA for use as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma. [Spectrum Pharmaceuticals] 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 Full Professorship – Radiopharmaceutical Development (German Cancer Research Center)

Postdoctoral Fellow – Prostate Epithelial Homeostasis and Carcinogenesis (Baylor College of Medicine)

Senior Scientist – Immune-Oncology (PTM Biolabs Inc.)

Research Technician – Nutrition and Cancer (St. Anne’s University Hospital)

Postdoctoral Fellowship – Cancer Research (Universitat Pompeu Fabra)

Postdoctoral Fellow – Cancer Stem Cell Research (Fred Hutchinson Cancer Research Center)

Director – Cancer Genomics (Ontario Institute for Cancer Research)

Postdoctoral Fellow – Cancer Genomics (The Cancer Institute of New Jersey)

Postdoctoral Fellow – Breast and Ovarian Cancer (Johns Hopkins University School of Medicine)

Postdoctoral Fellow – Division of Cancer Biology (Case Western Reserve University)

Tenure Track Position – Cancer Biology (University of Texas MD Anderson Cancer Center)

Postdoctoral Fellowship – Various Projects (University of Cincinnati)

PhD Studentship – Peptide Receptors in Cancer Stem Cells (Exiris/Bielefeld University)

Postdoctoral Fellowship – Cancer Stem Cell Biology (McGill University Health Center)

Translational Research Scientist – Hematology and Oncology (University of Chicago)

Faculty Position – Cancer Research (Various Areas) (The Jackson Laboratory)

Staff Scientist – Cell Therapy Process Development (Fred Hutchinson Cancer Research Center)

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