Cancer Stem Cell News Volume 6.03 | Jan 25 2017

TOP STORY

Researchers Find New Way to Target Blood Stem Cell Cancers

A protein-sugar molecule, CD99, occurs more frequently than normal on stem cells responsible for blood cancers, including acute myeloid leukemia (AML) and the related myelodysplastic syndromes. Building on this discovery, the authors designed an antibody that recognizes and destroys CD99-covered leukemia cells while sparing normal blood stem cells, a finding confirmed by experiments in human cells and in mice with AML cells. [Press release from NYU Langone Medical Center (PR Newswire Association LLC.) discussing online prepublication in Science Translational Medicine] Press Release | Abstract

(Ranked by impact factor of the journal)

FOXM1 Recruits Nuclear Aurora Kinase A to Participate in a Positive Feedback Loop Essential for the Self-Renewal of Breast Cancer Stem Cells

Investigators report that nuclear Aurora kinase A (AURKA) can be recruited by Forkhead box subclass M1 (FOXM1) as a co-factor to transactivate FOXM1 target genes in a kinase-independent manner. They showed that AURKA and FOXM1 participate in a tightly coupled positive feedback loop to enhance breast cancer stem cells phenotype. [Oncogene] Full Article

Aryl Hydrocarbon Receptor/Cytochrome P450 1A1 Pathway Mediates Breast Cancer Stem Cells Expansion through PTEN Inhibition and β-Catenin and Akt Activation

Scientists designed this study to a) determine the effect of aryl hydrocarbon receptor (AhR) activation and inhibition on breast cancer stem cells (CSCs) development, maintenance, self-renewal, and chemoresistance at the in vitro and in vivo levels and b) explore the role of β-Catenin, PI3K/Akt, and PTEN signaling pathways. The constitutive mRNA expression and cellular content of CYP1A1 and CYP1B1, AhR-regulated genes, were markedly higher in CSCs more than differentiating non-CSCs of five different human breast cancer cells. [Mol Cancer] Full Article

Highly Potent Non-Carboxylic Acid Autotaxin Inhibitors Reduce Melanoma Metastasis and Chemotherapeutic Resistance of Breast Cancer Stem Cells

Researchers report on inhibitors of autotaxin (ATX) derived by lead optimization of the benzene-sulfonamide in silico hit compound 3. The new analogues provided a comprehensive SAR of the benzene-sulfonamide scaffold that yielded a series of highly potent ATX inhibitors. In particular, compound 3b potently reduced in vitro chemotherapeutic resistance of 4T1 breast cancer stem-like cells to paclitaxel and reduced significantly B16 melanoma metastasis in vivo. [J Med Chem] Abstract

Hepatitis B Virus X Protein Promotes the Stem-Like Properties of OV6⁺ Cancer Cells in Hepatocellular Carcinoma

Investigators showed that the concomitant expression of hepatitis B virus X protein (HBx) and OV6 was closely associated with the clinical outcomes and prognosis of patients with HBV-related hepatocellular carcinoma. HBx was required for the stem-like properties of OV6⁺ liver cancer stem-like cells, including self-renewal, stem cell-associated gene expression, tumorigenicity and chemoresistance. [Cell Death Dis] Full Article

H19/let-7/LIN28 Reciprocal Negative Regulatory Circuit Promotes Breast Cancer Stem Cell Maintenance

Researchers showed that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Mechanistically, they found that H19 functions as a competing endogenous RNA to sponge miRNA let-7, leading to an increase in expression of a let-7 target, the core pluripotency factor LIN28, which is enriched in BCSC populations and breast patient samples. [Cell Death Dis] Full Article

The Role of the Cancer Stem Cell Marker CD271 in DNA Damage Response and Drug Resistance of Melanoma Cells

Investigators observed high cell surface and total levels of nerve growth factor receptor/CD271, a marker of melanoma-initiating cells, in sub-populations of chemoresistant cell lines. CD271 expression was increased in drug-sensitive cells but not resistant cells in response to DNA-damaging chemotherapeutics etoposide, fotemustine and cisplatin. [Oncogenesis] Full Article

Bisacodyl and Its Cytotoxic Activity on Human Glioblastoma Stem-Like Cells. Implication of Inositol 1,4,5-Triphosphate Receptor Dependent Calcium Signaling

Researchers performed a differential screening of the Prestwick Chemical Library of approved drugs on both proliferating and quiescent glioblastoma stem-like cells and identified bisacodyl as a cytotoxic agent with selectivity for quiescent glioblastoma stem-like cells. They further characterized bisacodyl activity and show its efficacy in vitro on clonal macro-tumorospheres, as well as in vivo in glioblastoma mouse models. [Biochim Biophys Acta] Abstract

Progressive Enrichment of Stemness Features and Tumor Stromal Alterations in Multistep Hepatocarcinogenesis

The authors investigated the expression status of stemness markers and tumor stromal changes in B viral carcinogenesis, which is the main etiology of hepatocellular carcinoma (HCC) in Asia. Stemness features were progressively acquired during hepatocarcinogenesis in combination with enrichment of stromal cells. The stemness features and tumor stromal alterations also peaked in less differentiated or larger HCCs. [PLoS One] Full Article

Systemic T Cells Immunosuppression of Glioma Stem Cell-Derived Exosomes Is Mediated by Monocytic Myeloid-Derived Suppressor Cells

Scientists investigated the immunomodulatory properties of glioma-stem cells (GSC)-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes. In unfractionated PBMCs, GSC-derived exosomes inhibited T cell activation, proliferation and Th1 cytokine production, and did not affect cell viability or regulatory T-cell suppression ability. [PLoS One] Full Article

MicroRNA-145 Inhibits Tumorigenesis and Invasion of Cervical Cancer Stem Cells

High expression of miR-145 indicates a good prognosis in cancer patients, but its role in cervical cancer stem cells (CCSCs) is not known. The authors showed that expression of miR-145 and core stem cell transcription factors, Sox2, Nanog and Oct4, are associated with the pluripotency of CCSCs, with increased expression of miR-145 after cervical tumorsphere differentiation. [Int J Oncol] Abstract

Identifying and Targeting Cancer Stem Cells in the Treatment of Gastric Cancer

Because gastric cancer can originate from cancer stem cells (CSCs), the authors review current targets of signaling pathways for CSCs in gastric cancer that are being studied in clinical trials. These pathways are known to regulate the self-renewal and differentiation process in gastric CSCs. A better understanding of the clinical results of trials that target gastric CSCs will lead to better outcomes for patients with gastric cancer. [Cancer] Abstract

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

Boston Biomedical Presents Clinical Data on First-in-Class Cancer Stemness Inhibitor Napabucasin

Boston Biomedical presented data from two clinical studies for its lead investigational compound, napabucasin. In a Phase Ib/II study of napabucasin – an orally administered investigational agent designed to inhibit cancer stemness pathways by targeting STAT3 – colorectal cancer patients who were FOLFIRI-naïve and those previously treated with FOLFIRI showed signs of anti-cancer activity when napabucasin was administered in combination with FOLFIRI with and without bevacizumab. [Press release from Boston Biomedical discussing research presented at the 2017 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, San Francisco] Press Release | Abstract 1 | Abstract 2

OncoMed Initiates Enrollment of Phase Ib Clinical Trial of Brontictuzumab for the Treatment of Metastatic Colorectal Cancer Patients

OncoMed Pharmaceuticals, Inc. announced dosing of the first patient in a Phase Ib clinical trial of brontictuzumab plus chemotherapy in patients with metastatic colorectal cancer. [OncoMed Pharmaceuticals, Inc.] Press Release

Statement from FDA Commissioner Robert Califf, M.D. Announcing FDA Oncology Center of Excellence Launch

The U.S. Food and Drug Administration (FDA) established the Oncology Center of Excellence and appointed Dr. Richard Pazdur as its director. This will make oncology the first disease area to have a coordinated clinical review of drugs, biologics and devices across the agency’s three medical product centers. [U.S. Food and Drug Administration] Press Release

Candidates from Ethiopia, United Kingdom, and Pakistan Will Compete for WHO’s Top Slot

The World Health Organization (WHO) announced who will be up for election to the post of director-general in May. They are: former Ethiopian health minister and minister of foreign affairs Tedros Adhanom Ghebreyesus; British physician and United Nations official David Nabarro; and Pakistani cardiologist and former science minister Sania Nishtar. [ScienceInsider] Editorial

Memo Freezing NIH Communications with Congress Triggers Jitters

Is the National Institutes of Health (NIH) part of the clampdown by the Trump administration on communications at science agencies? That’s how some are reacting to White House directive telling NIH to halt correspondence with public officials and hold off on new policies. But some observers say the NIH directive is not unusual for a new administration. [ScienceInsider] Editorial

NEW 4^th Immunotherapy of Cancer Conference
March 20-22, 2017
Prague, Czech Republic

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

NEW Research Fellow – Cancer and Stem Cell Biology (National University of Singapore)

Research Associate/Assistant – Leukemia & Stem Cell Biology (King’s College London)

Principal Scientist – Oncology (Janssen)

Postdoctoral Research – Cancer Genetics and Epigenetics (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Brain Cancer Stem Cells (University of Alabama at Birmingham)

Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Viruses & Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Liver Cancer and Developmental Biology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cell Cycle Control and Tumorigenesis (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Ubiquitin System and Cancer (Fred Hutchinson Cancer Research Center)

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