Cancer Stem Cell News Volume 8.25 | Jul 3 2019

TOP STORY

Myc Targeted CDK18 Promotes ATR and Homologous Recombination to Mediate PARP Inhibitor Resistance in Glioblastoma

CDK18 knockdown or ATR inhibition in glioblastoma stem-like cells (GSCs) suppressed homologous recombination and conferred PARP inhibitor (PARPi) sensitivity, with ATR inhibitors synergizing with PARPis or sensitizing GSCs. ATR inhibitor VE822 combined with PARPi extended survival of mice bearing GSC-derived orthotopic tumors, irrespective of PARPi-sensitivity. [Nat Commun] Full Article

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TSPAN8 Promotes Cancer Cell Stemness via Activation of Sonic Hedgehog Signaling

Scientists report that TSPAN8 expression was upregulated in breast CSCs, promoted the expression of the stemness genes NANOG, OCT4, and ALDHA1, and correlated with therapeutic resistance. Mechanistically, TSPAN8 interacted with PTCH1 and inhibited the degradation of the SHH/PTCH1 complex through recruitment of deubiquitinating enzyme ATXN3. [Nat Commun] Full Article

Impairing Temozolomide Resistance Driven by Glioma Stem-Like Cells with Adjuvant Immunotherapy Targeting O-Acetyl GD2 Ganglioside

Using patient-derived glioblastoma cells researchers found that glioma stem-like cells over-expressed O-acetyl-GD2. As a result, monoclonal antibody 8B6 immunotherapy significantly increased temozolomide genotoxicity and tumor cell death in vitro by enhancing temozolomide tumor uptake. [Int J Cancer] Abstract

Breast Cancer Stem Cells with Tumor- versus Metastasis-Initiating Capacities Are Modulated by TGFBR1 Inhibition

The authors studied the overlap between metastatic stem cells and tumor-initiating cells in the MMTV-PyMT model. They showed that in the MMTV-PyMT model, Lin^–CD90^–ALDH^high cells retained a high tumor-initiating potential in orthotopic transplants, in contrast to Lin^–CD24⁺CD90⁺, which retained higher metastatic capacity. [Stem Cell Reports] Full Article | Graphical Abstract

IL-32γ Suppresses Lung Cancer Stem Cell Growth via Inhibition of ITGAV-Mediated STAT5 Pathway

Tumor-sphere formation and cell viability assay revealed a greater inhibition of CSC proliferation and antineoplastic activity of IL-32γ in CD133⁺ CSCs as compared with normal cancer cells. The inhibitory effects of IL-32γ on tumor development were associated with inhibition of the STAT5 pathway. In addition, inhibition of STAT5 increased cleavage of caspase-3, but suppressed CD133 expression and colony formation. [Cell Death Dis] Full Article

Comparative Transcriptomic Analysis of Temozolomide Resistant Primary GBM Stem-Like Cells and Recurrent GBM Identifies Up-Regulation of the Carbonic Anhydrase CA2 Gene as Resistance Factor

Scientists describe consistent up-regulation of ccarbonic anhydrase 2 (CA2) not only in temozolomide (TMZ) resistant glioblastoma (GBM) stem-like cells on mRNA and protein level, but also in patient-matched clinical samples of first manifest and recurrent tumors. Co-treatment with the carbonic anhydrase inhibitor acetazolamid sensitized cells to TMZ induced cell death. [Cancers] Full Article

Hormonal Regulation of Patient-Derived Endometrial Cancer Stem-Like Cells Generated by Three-Dimensional Culture

Investigators established long-term culturable patient-derived cancer cells (PDCs) from patient endometrial tumors by spheroid cell culture, which is favorable for the enrichment of CSCs. PDC-derived xenograft tumors were generated in immunodeficient NOG mice. Morphologically, PDCs derived from three distinct patient samples and their xenograft tumors recapitulated the corresponding original patient tumors. [Endocrinology] Abstract

Targeting of Replicating CD133 and OCT4/SOX2 Expressing Glioma Stem Cells Selects a Cell Population That Reinitiates Tumors upon Release of Therapeutic Pressure

The authors determined if a therapeutic strategy specifically targeting glioblastoma (GBM) stem cells (GSCs) would completely eradicate a GBM tumor. In both the in vitro and the in vivo models, ganciclovir therapy targeting proliferating GSCs promoted the survival of a quiescent, stem-like cell pool capable of reproducing the tumor upon release of the therapeutic pressure. [Sci Rep] Full Article

Monospecific Antibody Targeting of CDH11 Inhibits Epithelial-to-Mesenchymal Transition and Represses Cancer Stem Cell-Like Phenotype by Up-Regulating miR-335 in Metastatic Breast Cancer, In Vitro and In Vivo

Researchers demonstrated that exposure to anti-CDH11 antibody suppressed metastasis, reduced CDH11, fibronectin and β-catenin expression, and abrogated the CSC-like traits of metastatic breast cancer (MBC) cells. Ectopic expression of miR-335 suppressed CDH11, β-catenin and vimentin expression, in concert with attenuated metastatic and CSC potentials of the MBC cells; conversely, inhibition of miR-335 resulted in increased metastatic potential. [BMC Cancer] Full Article

Sotrastaurin Attenuates the Stemness of Gastric Cancer Cells by Targeting PKCδ

Investigators found that protein kinase C-δ (PKCδ) positively regulated the metastasis, chemoresistance, and stem cell-like characteristics of gastric cancer cells, and its inhibitor sotrastaurin could rescue the above effects mediated by PKCδ. [Biomed Pharmacother] Abstract

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Cellular and Molecular Biology of Cancer Stem Cells in Melanoma: Possible Therapeutic Implications

Malignant melanoma is a tumor characterized by a very high level of heterogeneity, responsible for its malignant behavior and ability to escape from standard therapies. The authors highlight the molecular and biological features of the subpopulation of CSCs, well known to be characterized by self-renewal properties, deeply involved in triggering the processes of tumor generation, metastasis, progression and drug resistance. [Semin Cancer Biol] Abstract

Ovarian Cancer Stemness: Biological and Clinical Implications for Metastasis and Chemotherapy Resistance

Investigators review the current understanding of the cell-biological mechanisms that regulate ovarian cancer metastasis and chemotherapy resistance, with a pivotal focus on ovarian cancer stem cells, and discuss the potential clinical implications of evolving cancer stem cell research and resultant novel therapeutic approaches. [Cancers] Full Article

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Ziopharm Oncology Initiates Phase II Trial Evaluating Combination Therapy of Controlled IL-12 with Libtayo^® (Cemiplimab-Rwlc) to Treat Patients with Recurrent Glioblastoma

Ziopharm Oncology, Inc. announced the initiation of a Phase II clinical trial evaluating controlled IL-12, in combination with PD-1 antibody Libtayo^® for the treatment of recurrent or progressive glioblastoma multiforme in adults. The multi-center trial will be conducted at approximately ten hospitals specializing in the treatment of brain cancers in the United States. [Ziopharm Oncology, Inc.] Press Release

Precigen Announces First Patient Dosed in Phase I/Ib Study of PRGN-3006 UltraCAR-T™ in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML) or Higher Risk Myelodysplastic Syndrome (MDS)

Precigen, Inc. announced that the first patient has been dosed with PRGN-3006, a first-in-class investigational therapy using Precigen’s non-viral UltraCAR-T™ therapeutic platform. [Precigen, Inc. (PR Newswire Association LLC.)] Press Release

Taiwan to Crack Down on Unauthorized Research Collaborations With Mainland China

According to Taiwan’s Central News Agency, the island’s government is investigating seven researchers for allegedly joining a prestigious program sponsored by the mainland China government to lure academics to the mainland without the necessary permissions. [Nature News] Editorial

India Culls Hundreds More ‘Dubious’ Journals From Government Approved List

A rise in Indian scientists publishing research in low-quality journals prompted the University Grants Commission to create a ‘white list’ of approved journals in 2017. Universities use the list to evaluate researchers for promotion and hiring. [Nature News] Editorial

NEW 5^th International Conference Acute Myeloid Leukemia Molecular and Translational: Advances in Biology and Treatment
October 24-26, 2019
Estoril, Portugal

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NEW Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University)

NEW Postdoctoral Research Position – B-Cell Acute Lymphoblastic Leukemia Research (University of California San Francisco)

Research Scientist – Leukemia Stem/Progenitor Cell Research (MD Anderson Cancer Center)

Postdoctoral Scientist – Cancer Organoids (Rutgers Cancer Institute of New Jersey)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Fellow – Jak-Stat Signaling in Prostate & Pancreatic Cancer (Medical College of Wisconsin)

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)

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