Cancer Stem Cell News Volume 7.29 | Jul 25 2018

TOP STORY

Targeting Stromal Remodeling and Cancer Stem Cell Plasticity Overcomes Chemoresistance in Triple Negative Breast Cancer

Stromal treatment of patient-derived xenografts with smoothened inhibitors downregulated CSC markers expression and sensitized tumors to docetaxel, leading to markedly improved survival and reduced metastatic burden. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Metabolic Reprogramming by Dual AKT/ERK Inhibition through Imipridones Elicits Unique Vulnerabilities in Glioblastoma

Imipridones affected energy metabolism by suppressing both glycolysis and oxidative phosphorylation, which was accompanied by a compensatory activation of the serine-one carbon-glycine (SOG) pathway, involving the transcription factor ATF4. Interference with the SOG pathway through novel inhibitors of PHGDH resulted in synergistic cell death induction in vitro and in vivo. [Clin Cancer Res] Abstract

A SIRT1-Centered Circuitry Regulates Breast Cancer Stemness and Metastasis

Researchers identifed a SIRT1-PRRX1-KLF4-ALDH1 circuitry, which coupled CSCs, chemo-resistance, metastasis and aging. Pro-longevity protein SIRT1 deacetylated and stabilized the epithelial-to-mesenchymal-transition inducer PRRX1, which inhibited the transcription of core stemness factor KLF4. KLF4 inhibitor kenpaullone sensitized breast cancer cells and xenograft tumors to paclitaxel and improved therapeutic effects. [Oncogene] Full Article

USP17 Mediates Macrophage-Promoted Inflammation and Stemness in Lung Cancer Cells by Regulating TRAF2/TRAF3 Complex Formation

TNFR-associated factor (TRAF) 2-binding and TRAF3-binding motifs were identified in ubiquitin-specific peptidase 17 (USP17), through which it interacted with and disrupted the TRAF2/TRAF3 complex. This stabilized its client proteins, enhanced inflammation and stemness in cancer cells, and promoted macrophage recruitment. [Oncogene] Full Article

The Long Non-Coding RNA n339260 Promotes Vasculogenic Mimicry and Cancer Stem Cell Development in Hepatocellular Carcinoma

The authors demonstrated that expression of the lncRNA, n339260, was associated with CSCs phenotype in hepatocellular carcinoma, and n339260 level correlated with the vasculogenic mimicry (VM), metastasis, and shorter survival time in an animal model. Using a short hairpin RNA approach, n339260 was silenced in tumor cells, and knockdown of n339260 was associated with reduced VM and CSCs. [Cancer Sci] Abstract

HDAC Inhibitor Suppresses Proliferation and Tumorigenicity of Drug-Resistant Chronic Myeloid Leukemia Stem Cells through Regulation of Hsa-miR-196a Targeting BCR/ABL1

Scientists documented the essential role of the interplay between histone deacetylases, the polycomb group proteins, pluripotency transcription factors and the cell cycle machinery in the viability, oncogenicity and therapy evasion of imatinib mesylate-resistant CD34+/CD38- chronic myeloid leukemia stem cells. [Exp Cell Res] Abstract | Graphical Abstract

miR-140-5p Inhibits the Proliferation and Enhances the Efficacy of Doxorubicin to Breast Cancer Stem Cells by Targeting Wnt1

Investigators demonstrated that miR-140-5p was frequently downregulated in breast cancer stem cells (BCSCs), and miR-140-5p mimics could inhibit the proliferation of BCSCs. miR-140 mimics could enhance the sensitivity of BCSCs to doxorubicin through the Wnt1/ABCB1 pathway both in vitro and in vivo. [Cancer Gene Ther] Abstract

CLT030, a Leukemic Stem Cell–Targeting CLL1 Antibody-Drug Conjugate for Treatment of Acute Myeloid Leukemia

C-type lectin domain family 12 member A (CLL1)-antibody-drug conjugate (CLT030) inhibited in vitro leukemic stem cell colony formation and demonstrated robust in vivo efficacy in acute myeloid leukemia (AML) cell tumor models and tumor growth inhibition in the AML patient-derived xenograft model. [Blood Adv] Full Article | Press Release | Graphical Abstract

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Dysregulation of Iron Metabolism in Cancer Stem Cells

The authors describe the alterations of iron homeostasis occurring in CSCs, which in general are characterized by high intracellular iron content. They also discuss iron-dependent mechanisms as druggable pathways, as iron chelators have been considered for tumor therapy and new molecules currently proposed and studied as antineoplastic drugs may impinge on iron and its capacity to promote oxidative stress to have therapeutic value in cancer. [Free Radic Biol Med] Abstract | Graphical Abstract

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

Rally Foundation for Childhood Cancer Research Makes Second Grant to National Brain Tumor Society

National Brain Tumor Society announced that it will receive a $100,000 Rally for Research Grant from the Rally Foundation for Childhood Cancer Research to support the organization’s Defeat Pediatric Brain Tumors Research Collaborative. [National Brain Tumor Society] Press Release

FDA Grants Approval of TIBSOVO^®, the First Oral, Targeted Therapy for Adult Patients with Relapsed/Refractory Acute Myeloid Leukemia and an IDH1 Mutation

Agios Pharmaceuticals, Inc. announced that TIBSOVO^® was granted approval from the US FDA for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA approved test. [Agios, Inc.] Press Release

Tolero Pharmaceuticals Advances Investigational Agent Alvocidib into Second Stage of Phase II Zella 201 Study in Patients with Relapsed Refractory MCL-1-Dependent AML

Tolero Pharmaceuticals, Inc. announced that it has initiated the second stage of the Phase II Zella 201 study evaluating the efficacy and safety of alvocidib, a potent CDK9 inhibitor, in combination with cytarabine and mitoxantrone in patients with relapsed or refractory MCL-1-dependent acute myeloid leukemia (AML). [Tolero Pharmaceuticals, Inc.] Press Release

Innovest Global Announces Patent is Approved for StemVax Therapeutics

Innovest Global Inc. reports that the patent application for the technology being developed by StemVax Therapeutics was approved. The patent is granted under the category of “Cancer Antigens”, and related to the “treatment of cancer using vaccination therapy”. [Innovest Global, Inc.] Press Release

Third Retraction for Harvard Cancer Biologist

Nature has issued a retraction of a cancer study, seven years after its publication, citing issues with two figures and the unavailability of original data for them. [The Scientist] Editorial

New Evidence USCIS Policies Increased Denials Of H-1B Visas

New data show that in 2017, U.S. Citizenship and Immigration Services (USCIS) denied many more H-1B petitions and issued numerous costly Requests for Evidence to stop highly educated foreign nationals from working in America. [Forbes Media LLC] Editorial

UK Labs Made 1.9 Million Transgenic Animals Last Year

The production of genetically modified animals for research has leveled off in UK laboratories, after a decade that saw a 37% rise in the number bred. Last year, 1.9 million of these animals were produced, about the same as the year before, according to annual statistics released by the UK government. [Nature News] Editorial

NEW 60^th American Society of Hematology (ASH) Annual Meeting & Exposition
December 1-4, 2018
San Diego, California, United States

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

NEW Group Leader Positions – Precision Medicine (Italian Institute for Genomic Medicine)

Postdoctoral Fellow – Cancer Research (The University of Texas MD Anderson Cancer Center)

Postdoctoral Scholar – Statistical Bioinformatics (The University of Iowa)

Postdoctoral Positions – Gene Regulation and/or Cancer Biology (University of North Carolina at Chapel Hill School of Medicine)

Postdoctoral Researcher – Cancer Stem Cells and Epitranscriptomics (University of California San Diego)

Postdoctoral Fellowship – Structure-Based Studies for a Search of New Drug Leads for Leukemia Treatment (European Molecular Biology Laboratory)

Postdoctoral Scientist – Drug Discovery & Cancer Stem Cell Biology (Cancer Research UK Manchester Institute)

Postdoctoral Fellow – Cancer Biology (Children’s Cancer Therapy Development Institute)

Tenure-Track Faculty Positions – Various (The Ohio State University)

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

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

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