Cancer Stem Cell News Volume 8.21 | June 5 2019

TOP STORY

New Markers for Human Ovarian Cancer That Link Platinum Resistance to the Cancer Stem Cell Phenotype and Define New Therapeutic Combinations and Diagnostic Tools

Scientists used bioinformatics analysis of public databases and RT-qPCR to quantitate the relative gene expression profiles of ovarian tumors. Many of the dysregulated genes were CSC factors, and they analyzed its relation to therapeutic resistance in human primary tumors. They also performed clustering and in vitro analyses of therapy cytotoxicity in tumorspheres. [J Exp Clin Cancer Res] Full Article

(Ranked by impact factor of the journal)

Controlling Distinct Signaling States in Cultured Cancer Cells Provides a New Platform for Drug Discovery

Investigators cultured three primary human brain cancer cell lines under three different culture conditions that maintained low, medium, and high hairy and enhancer of split 3 (HES3) expression and characterized gene regulation and mechanical phenotype in these states. They assessed gene expression regulation following HES3 knockdown in the HES3-high conditions. [FASEB J] Abstract | Press Release

Cancer Stem Cells Contribute to Angiogenesis and Lymphangiogenesis in Serous Adenocarcinoma of the Ovary

Using spheroids as an in vitro model for CSCs, scientists evaluated their role in primary malignant cells (PMCs) in ascites from previously untreated patients with high-grade serous adenocarcinoma of ovary and cell lines. Spheroids from PMCs grown under specific conditions showed significantly higher expression of endothelial, pericyte and lymphatic endothelial markers. [Angiogenesis] Abstract

The NFL-TBS.40–63 Peptide Targets and Kills Glioblastoma Stem Cells Derived from Human Patients and Also Targets Nanocapsules into These Cells

The authors showed that the peptide entered in brain tumor-initiating cells and demonstrated an anti-tumor effect by inhibiting their proliferation and inducing their death through an alteration of their microtubule network and cell-cell adhesion, and a decrease in the self-renewal ability of these cancer stem cells. [Int J Pharm] Abstract | Graphical Abstract

Combining 1,3-Ditriazolyl-Benzene and Quinoline to Discover a New G-Quadruplex Interactive Small Molecule Active against Cancer Stem-Like Cells

Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′-(4,4’‐(1,3-phenylene)bis(1H-1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) (1d) showed the greater activity. Importantly, dose-response curves showed that 1d was cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemo-resistance. [ChemMedChem] Abstract

A Novel Bispecific c-MET/CTLA-4 Antibody Targeting Lung Cancer Stem Cell-Like Cells with Therapeutic Potential in Human Non-Small-Cell Lung Cancer

Investigators showed that bispecific antibody-5 (BsAb-5) could inhibit hepatocyte growth factor (HGF) mediated tumor development, including proliferation, migration, and apoptosis, serving as an inhibitory cellular mesenchymal-to-epithelial transition factor (c-MET) antibody. Mechanisms responsible for BsAb-5 in CD166⁺ lung CSCs included inducing c-MET degradation and inhibition of HGF-stimulated c-MET-Notch pathway. [Biosci Rep] Full Article

CD146 Is Highly Expressed in Glioma Stem Cells and Acts as a Cell Cycle Regulator

CD146 knockdown in glioma stem cells (GSCs) significantly compromised cell growth. Cell cycle analysis revealed that most of the CD146 and CD133 double-positive cells were in the G2/M phase. Ectopic expression of CD146 in parental glioma cells resulted in cell cycle arrest of most differentiated cells in G0/G1 phase. In contrast, ectopic expression of CD146 in GSCs resulted in an increase in the number of CD133-positive cells in the G2/M phase. [J Neurooncol] Abstract

Single-Cell RNA Sequencing Reveals the Impact of Chromosomal Instability on Glioblastoma Cancer Stem Cells

The authors performed single-cell RNA sequencing on a chromosomally unstable glioblastoma CSC line and a control normal, diploid neural stem cell line to investigate the impact of copy number variation due to chromosomal instability on gene expression. [BMC Med Genomics] Full Article

Linkage between EMT and Stemness State through Molecular Association between TWIST1 and NY-ESO1 in Esophageal Squamous Cell Carcinoma

A number of cancer testis antigens can induce epithelial mesenchymal transition (EMT) process and promote CSC characteristics. Investigators analyzed the correlation between NY-ESO1 and TWIST1 in esophageal squamous cell carcinoma (ESCC), as well as their impact on the EMT process. [Biochimie] Abstract

Semaphorin-7A on Exosomes: A Promigratory Signal in the Glioma Microenvironment

Scientists describe that semaphorin7A is exposed on glioma-associated stem cell-exosomes’ surface and signals to glioma stem cells (GSCs) through integrin β1. This interaction activated focal adhesion kinase into GSC and increased their motility, in a patient-based in vitro model. [Cells] Abstract

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p63 at the Crossroads between Stemness and Metastasis in Breast Cancer

Investigators provide a broad picture on the physiological role of p63, in maintaining the basal epithelial identity, as well as its involvement in breast cancer progression, emphasizing its relevance in tumor cell invasion and stemness. [Int J Mol Sci] Full Article

Hypoxia- and MicroRNA-Induced Metabolic Reprogramming of Tumor-Initiating Cells

The authors summarize the current knowledge on environmental stress factors and how they affect the metabolism of tumor-initiating cells (TICs), with a special focus on miRNA- and hypoxia-induced effects on colon TICs. [Cells] Abstract | Download Full Article

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Medicenna Presents Clinical Validation of the IL4 Receptor as a Biomarker for MDNA55 in Recurrent Glioblastoma

The presentation by Dr. Dina Randazzo of Duke University School of Medicine and a Principal Investigator in the Phase IIb clinical trial MDNA55-05, which recently completed its enrollment, focused on the development of a new biomarker test for the interleukin-4 (IL4) receptor that may enable better selection and superior treatment outcomes for patients with recurrent glioblastoma, a highly aggressive and uniformly fatal form of brain cancer. [Press release from Medicenna Therapeutics Corp. discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Adastra Pharmaceuticals Announces Positive Interim Data from Phase Ib Clinical Trial of Zotiraciclib in the Treatment of Recurrent Malignant Gliomas

Adastra Pharmaceuticals, Inc. announced interim data from a Phase Ib trial of the company’s lead clinical candidate, zotiraciclib, in combination with temozolomide for the treatment of recurrent malignant gliomas. [Press release from Adastra Pharmaceuticals, Inc. (PR Newswire Association LLC.) discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Ziopharm Oncology Provides Positive Clinical Data for Controlled IL-12 for the Treatment of Recurrent Glioblastoma

Ziopharm Oncology, Inc. announced the presentation of new interim analyses of clinical data from two ongoing substudies in its Controlled IL-12 platform, or Ad-RTS-hIL-12 plus veledimex, both as monotherapy and in combination with a PD-1 inhibitor, for the treatment of recurrent or progressive glioblastoma multiforme in adults. [Press release from Ziopharm Oncology, Inc. discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Radiographic Analysis of VB-111 Phase II and III Clinical Trials in Recurrent Glioblastoma Shows Survival Benefit Associated with Objective Responses and Distinct Signature of VB-111 Activity

VBL Therapeutics announced that MRI data from VB-111 Phase II and Phase III studies in recurrent GBM, presented, showed a survival benefit associated with objective responses to the compound and a distinct signature of VB-111 activity. [Press release from VBL Therapeutics discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Origenis GmbH Announces Research Collaboration with US Cancer Center

Origenis GmbH announced that the company has entered into a collaboration with Memorial Sloan Kettering Cancer Center, New York, targeting glioblastoma, a rare but fatal brain cancer. Under the research and collaboration agreement, Origenis will use its proprietary AI platform for drug discovery and development. [Origenis GmbH] Press Release

BioTheryX Announces FDA Approval of IND Application to Initiate Phase I Clinical Trial in Relapsed or Refractory Acute Myeloid Leukemia

BioTheryX, Inc. announced that the FDA has cleared BioTheryX’s Investigational New Drug (IND) application for BTX-A51, an oral multi-kinase inhibitor, for the treatment of patients with relapsed/refractory acute myeloid leukemia or high-risk myelodysplastic syndrome. [BioTheryX, Inc. (PR Newswire Association LLC)] Press Release

US FDA Approves Supplemental New Drug Application Adding Overall Survival Data for XOSPATA^® (Gilteritinib)

Astellas Pharma Inc. announced that the FDA approved a supplemental New Drug Application to update the US product labeling for XOSPATA^® to include final analysis data from the ADMIRAL trial. The data demonstrated improvement in Overall Survival in those treated with gilteritinib monotherapy versus salvage chemotherapy in adult patients with relapsed or refractory acute myeloid leukemia with an FMS-like tyrosine kinase 3 mutation. [Astellas Pharma Inc.] Press Release

NIH Has Referred 16 Allegations of Foreign Influence on US Research to Investigators

The National Institutes of Health (NIH) has referred 16 allegations related to foreign influence of US-funded research to investigators and contacted 61 research institutions about such concerns, federal health officials said at a hearing. [STAT News] Editorial

Hungarians Protest against Proposed Government Takeover of Science

Thousands of scientists and their supporters marched through the streets of Budapest on 2 June to protest against a proposed law that would give the Hungarian government direct control of the country’s top research institutes. [Nature News] Editorial

NEW 6^th Annual European Congress on Clinical and Translational Medicine
October 18-20, 2019
Vienna, Austria

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

NEW Tier I Canada Research Chair – Precision & Molecular Oncology (University of Calgary)

Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University)

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)

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