Cancer Stem Cell News Volume 8.19 | May 22 2019

TOP STORY

Cysteine Depletion Targets Leukemia Stem Cells through Inhibition of Electron Transport Complex II

Given the role of cysteine in driving leukemia stem cell (LSC) energy production scientists tested cysteine depletion as a potential therapeutic strategy. Using a novel cysteine-degrading enzyme they demonstrated selective eradication of LSCs, with no detectable effect on normal hematopoietic stem/progenitor cells. [Blood] Abstract

(Ranked by impact factor of the journal)

The Antibiotic Clofoctol Suppresses Glioma Stem Cell Proliferation by Activating KLF13

Investigators took advantage of glioma stem cells (GSCs) as a cell model to perform high-throughput drug screening and the antibiotic, clofoctol, was identified as the most effective compound, showing reduction of colony-formation and induction of apoptosis in GSCs. Moreover, growth of tumors was inhibited in vivo after clofoctol treatment in primary patient-derived xenografts and transgenic xenografts. [J Clin Invest] Abstract | Full Article | Graphical Abstract

MEK Inhibitors Activate Wnt Signaling and Induce Stem Cell Plasticity in Colorectal Cancer

Truncating mutations of APC generated by CRISPR/Cas9 strongly synergized with MEK inhibitors in enhancing Wnt responses in isogenic colorectal cancer (CRC) models. Using patient-derived CRC organoids, the authors showed that MEK inhibition led to increased Wnt activity, elevated LGR5 levels and enrichment of gene signatures associated with stemness and cancer relapse. [Nat Commun] Full Article | Press Release

Wnt/IL-1β/IL-8 Autocrine Circuitries Control Chemoresistance in Mesothelioma Initiating Cells by Inducing ABCB5

Researchers clarify if and by which mechanisms the chemoresistant phenotype of malignant pleural mesothelioma (MPM)-initiating cells (ICs) was due to specific stemness-related pathways. They generated MPM ICs from primary MPM samples and compared the gene expression and chemo-sensitivity profile of IC and differentiated/adherent cells of the same patient. [Int J Cancer] Abstract

Nalbuphine Suppresses Breast Cancer Stem-Like Properties and Epithelial-Mesenchymal Transition via the AKT-NFκB Signaling Pathway

Nalbuphine suppressed cancer stem-like traits and epithelial-mesenchymal transition (EMT) in both breast cancer cells and mouse xenograft tumor tissues. Additionally, activation of AKT reversed the nalbuphine-induced inhibition of cancer stem-like properties, tumorigenesis and EMT. [J Exp Clin Cancer Res] Full Article

miR-29b/Sp1/FUT4 Axis Modulates the Malignancy of Leukemia Stem Cells by Regulating Fucosylation via Wnt/β-Catenin Pathway in Acute Myeloid Leukemia

Transcriptional inhibitor actinomycin D or translational inhibitor cycloheximide prevented leukemia stem cell (LSC) progression, and Sp1 was identified as the efficient regulator of FUT4 transcription. Moreover, miR-29b directly affected the binding of Sp1 and FUT4 promoter region, which further mediated LSC proliferation, apoptosis and drug-resistance through fucosylated-CD44 via the activation of the Wnt/β-catenin pathway. [J Exp Clin Cancer Res] Full Article

Combination of 5-Fluorouracil and Thymoquinone Targets Stem Cell Gene Signature in Colorectal Cancer Cells

Two principle stem cell regulatory pathways WNT/β-Catenin and PI3K/AKT were found to be downregulated after Combi and hybrid treatment. Furthermore, both treatments strikingly eliminated CD133⁺ CSC population, accompanying the depleted self-renewal capacity by eradicating long-term propagated 3D tumor cell spheres at sub-toxic doses. [Cell Death Dis] Full Article

Central Role of IP₃R2-Mediated Ca²⁺ Oscillation in Self-Renewal of Liver Cancer Stem Cells Elucidated by High-Signal ER Sensor

Investigators found that niche factor-stimulated Ca²⁺ oscillation was a signature feature of CSC-enriched Hep-12 cells and purified α2δ1⁺ CSC fractions from hepatocellular carcinoma cell lines. In Hep-12 cells, the Ca²⁺ oscillation frequency positively correlated with self-renewal potential. [Cell Death Dis] Full Article

Pre-Clinical Evaluation of Minnelide as a Therapy for Acute Myeloid Leukemia

Treatment with triptolide led to a significant decrease in the colony forming ability of acute myeloid leukemia cell lines as well as in the expression of stem cell markers. Additionally, it resulted in the cell cycle arrest in the G1/S phase with significant downregulation of c-Myc, a major transcriptional regulator mediating cancer cell growth and stemness. [J Transl Med] Full Article

Dichloroacetate Affects Mitochondrial Function and Stemness-Associated Properties in Pancreatic Cancer Cell Lines

Dichloroacetate (DCA) caused enhancement of reactive oxygen species production, mtDNA, and of the mitophagy-marker LC3B-II in two cell lines but reduced mitochondrial fusion markers only in BXPC-3. Notably, DCA downregulated the expression of the cancer stem cells markers CD24/CD44/EPCAM only in PANC-1 but inhibited spheroid formation/viability in both cell lines. [Cells] Full Article

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Repurposing Drugs as Pro-Oxidant Redox Modifiers to Eliminate Cancer Stem Cells and Improve the Treatment of Advanced Stage Cancers

The authors explore the repurposing of old drugs that cause pro-oxidative overload to overcome onset of resistance to chemotherapy and enhance chemotherapeutic responses, particularly against metastatic cancer. [Med Res Rev] Abstract

Overlapping Migratory Mechanisms between Neural Progenitor Cells and Brain Tumor Stem Cells

A better understanding of the intersection between neural progenitor cells and brain tumor stem cells (BTSCs) will provide a better comprehension of BTSCs’ invasive capacity and the molecular mechanisms that govern their migration and eventually lead to the development of new therapies to improve the prognosis of patients with malignant gliomas. [Cell Mol Life Sci] Abstract

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Kazia Enters Clinical Collaboration for Metastatic Brain Cancer with Alliance for Clinical Trials in Oncology

Kazia Therapeutics Limited announced that it has entered into a collaboration with the Alliance for Clinical Trials in Oncology Foundation. Alliance will launch a multi-centre Phase II study to investigate the potential use of Kazia’s investigational new drug, GDC-0084, alongside several other targeted cancer therapies, in the treatment of brain metastases. [Kazia Therapeutics Limited] Press Release

AbbVie Provides Update on Depatuxizumab Mafodotin (Depatux-M), an Investigational Medicine for Newly Diagnosed Glioblastoma, an Aggressive Form of Brain Cancer

AbbVie announced the Phase III INTELLANCE-1 study of depatuxizumab mafodotin in patients with newly diagnosed glioblastoma, whose tumors have epidermal growth factor receptor amplification, demonstrated no survival benefit for patients receiving Depatux-M at an interim analysis. [AbbVie Inc.] Press Release

Tocagen’s Toca 5 Pivotal Phase III Clinical Trial in Patients with Recurrent Brain Cancer Continues without Modification at Planned Interim Analysis

Tocagen Inc. announced the Toca 5 Phase III clinical trial evaluating Toca 511 & Toca FC in patients with recurrent high grade glioma continues without modification following a planned interim analysis of data conducted by an Independent Data Monitoring Committee. [Tocagen Inc.] Press Release

Cellectar Expands Third Cohort of Its Phase II CLOVER-1 Study of CLR 131

Cellectar Biosciences, Inc. announced that initial results from the third cohort of its ongoing Phase II CLOVER-1 study of CLR 131 have exceeded its pre-specified performance criteria. As a result, the company will expand the number of chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytic lymphoma and marginal zone lymphoma patients it will enroll in the cohort. [Cellectar Biosciences, Inc.] Press Release

Lixte Biotechnology’s LB-100 to Be Evaluated by the National Cancer Institute in a Clinical Study of LB-100’s Ability to Enter Recurrent Glioblastoma Multiforme Brain Tumors

Lixte Biotechnology Holdings, Inc. announced the opening of a pharmacologic study of the ability of its lead clinical compound, LB-100, to enter the brain and penetrate recurrent glioblastoma multiforme tumors in patients in which surgical removal of their cancers is indicated. The study is being conducted by the National Cancer Institute under a Cooperative Research and Development Agreement with Lixte. [Lixte Biotechnology Holdings, Inc. (GlobeNewswire, Inc.)] Press Release

Mustang Bio and Nationwide Children’s Hospital Receive Orphan Drug Designation for MB-108 (Oncolytic Virus C134) for the Treatment of Malignant Glioma

Mustang Bio, Inc. and Nationwide Children’s Hospital announced that the FDA has granted Orphan Drug Designation to MB-108 for the treatment of malignant glioma, a type of brain cancer with a median survival of less than 18 months. Nationwide Children’s has exclusively licensed oncolytic virus C134 to Mustang. [Mustang Bio, Inc.] Press Release

How European Scientists Will Spend €100 Billion

Politicians don’t win prizes for speed, but the European Union’s parliament and the leaders of its member states made record time this year when they hammered out an agreement that could supply researchers in Europe with more than €100 billion (US$113 billion) over seven years. [Nature News] Editorial

National Cancer Institute Will Stop Funding Nanotechnology Centers

The end to funding represents a “natural transition” from putting dedicated support into an emerging field to becoming a more mature research field that fits in with other cancer fields, says Piotr Grodzinski of the National Cancer Institute’s Nanodelivery Systems and Devices Branch, which oversees the Centers of Cancer Nanotechnology Excellence, to Science. [The Scientist] Editorial

NSF, NASA, NIST Would Get Funding Boosts under House Spending Bill

The National Science Foundation (NSF) would get a 7% budget increase, and NASA a 3.8% bump, under a 2020 spending bill approved by an appropriations panel of the US House of Representatives. The bill rejects cuts to those and other federal research agencies proposed by President Donald Trump’s administration. [ScienceInsider] Editorial

NEW 20^th Asia-Pacific Prostate Cancer Conference
September 24-26, 2019
Melbourne, Australia

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

NEW Faculty Positions – Cancer Research (The University of Texas MD Anderson Cancer Center)

Postdoctoral Position – Cancer Biology (Washington University School of Medicine)

BIH Johanna Quand Professorships for Women Scientists – Open Topic (Stiftung Charité and The Berlin Institute of Health)

Postdoctoral Fellow Position – Stem Cells in Colon Cancer (Vanderbilt University Medical Center)

Postdoctoral Position – Tumor Metabolism, Stem Cell Biology & Circadian Clock Distruption (University of California Irvine)

Principal Investigator – Cancer Research (Zhejiang University)

Research Associates – Cell Competition in Cancer (University of Bristol)

Postdoctoral Research Position – Molecular Biology and Cancer Research (Augusta University)

Postdoctoral Fellowship – Cancer and Glioma Stem Cell Biology (Cornell University)

Postdoctoral Fellow – Glioblastoma Multiforme Research (Max Delbrück Center for Molecular Medicine)

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