Cancer Stem Cell News Volume 8.23 | Jun 19 2019

TOP STORY

Glioma Stem Cell Specific Super Enhancer Promotes Polyunsaturated Fatty Acid Synthesis to Support EGFR Signaling

Glioma stem cells epigenetically upregulated ELOVL2, a key polyunsaturated fatty acid synthesis enzyme. Targeting ELOVL2 inhibited glioblastoma cell growth and tumor initiation. ELOVL2 depletion altered cellular membrane phospholipid composition, disrupted membrane structural properties, and diminished EGFR signaling through control of fatty acid elongation. [Cancer Discov] Abstract

(Ranked by impact factor of the journal)

Loss of EZH2 Reprograms BCAA Metabolism to Drive Leukemic Transformation

Researchers showed that EZH2 and NRasG12D mutations cooperatively induced progression of myeloproliferative neoplasms to highly penetrant, transplantable and lethal myeloid leukemias in mice. EZH1, an EZH2 homolog, was indispensable for EZH2-deficient leukemia-initiating cells and constituted an epigenetic vulnerability. [Cancer Discov] Abstract

Non-Proteolytic Ubiquitination of Hexokinase 2 by HectH9 Controls Tumor Metabolism and Cancer Stem Cell Expansion

Investigators showed that HectH9 deficiency impeded tumor glucose metabolism and growth by hexokinase 2 (HK2) inhibition. The HectH9/HK2 pathway regulated CSC expansion and CSC-associated chemoresistance. Histological analyses showed that HectH9 expression was upregulated and correlated with disease progression in prostate cancer. [Nat Commun] Full Article

Multiple Cancer Pathways Regulate Telomere Protection

Scientists found that inhibition of several kinases of the Ras pathway, including ERK and MEK, recapitulated the effects of Trf1 genetic deletion, including induction of telomeric DNA damage, telomere fragility, and inhibition of cancer stemness. They showed that both bRAF and ERK2 kinases phosphorylatd TRF1 in vitro and that these modifications were essential for TRF1 location to telomeres in vivo. [EMBO Mol Med] Full Article | Press Release | Graphical Abstract

Transcriptomic Analysis Reveals That BMP4 Sensitizes Glioblastoma Tumor-Initiating Cells to Mechanical Cues

The authors showed that tumor-initiating cell (TIC) differentiation induced by bone morphogenetic protein 4 (BMP4) suppressed expression of proteins relevant to extracellular matrix signaling and sensitized TIC spreading to matrix stiffness. [Matrix Biol] Abstract

ALDH1A1 in Patient-Derived Bladder Cancer Spheroids Activates Retinoic Acid Signaling Leading to TUBB3 Overexpression and Tumor Progression

CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), a critical enzyme that synthesizes retinoic acid (RA), was abundantly expressed in patient-derived cancer cells (PDCs). ALDH1A1 inhibitors and shRNAs repressed both PDC proliferation and spheroid formation, whereas all-trans RA could rescue ALDH1A1 shRNA-suppressed spheroid formation. [Int J Cancer] Abstract

s-SHIP Promoter Expression Identifies Mouse Mammary Cancer Stem Cells

Researchers showed that in mammary tumors originating in bitransgenic mice, s-SHIP promoter expression enriched a rare cell population with CSC activity as demonstrated by sphere-forming assays in vitro and limiting dilution transplantation in vivo. These s-SHIP-positive CSCs were characterized by lower expression of delta-like non-canonical Notch ligand 1, a negative regulator of the Notch pathway. [Stem Cell Reports] Full Article

Heart Failure Drug Proscillaridin A Targets MYC Overexpressing Leukemia through Global Loss of Lysine Acetylation

Proscillaridin A anticancer activity was investigated against a panel of human leukemia and solid tumor cell lines with different MYC expression levels, overexpression in vitro systems and leukemia stem cells. RNA-sequencing and differentiation studies were used to characterize transcriptional and phenotypic changes. [J Exp Clin Cancer Res] Full Article

A Role for Kinesin-1 Subunits KIF5B/KLC1 in Regulating Epithelial Mesenchymal Plasticity in Breast Tumorigenesis

Investigators found kinesin family member 5B (KIF5B) to be expressed in triple negative-basal-like/claudin low breast cancer subtype and to be an inducer of epithelial-mesenchymal transition (EMT), stemness, invasiveness, tumor formation and metastatic colonization. [EBioMedicine] Full Article

Aquaporin 3 Maintains the Stemness of CD133⁺ Hepatocellular Carcinoma Cells by Activating STAT3

Scientists proved the carcinogenesis roles of aquaporin 3 (AQP3) in hepatocellular carcinoma and demonstrated that AQP3 promoted the stem cell-like properties of hepatoma cells by regulating CD133 expression. [Cell Death Dis] Full Article

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The Molecular Markers of Cancer Stem Cells in Head and Neck Tumors

As CSCs have been implicated in tumor cell survival, progression, and response to therapy, the identification of this tumor subpopulation would have important therapeutic and prognostic implications. [J Cell Physiol] Abstract

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Medicenna Presents Preliminary Top-Line Clinical Results from Their Phase IIb Trial of MDNA55 in Recurrent Glioblastoma

Medicenna Therapeutics Corp. presented preliminary top-line clinical results from their Phase IIb trial of MDNA55, an IL4-guided toxin, in patients with recurrent glioblastoma, the most common and uniformly fatal form of brain cancer. [Press release from Medicenna Therapeutics Corp. discussing research presented at the 2019 Immuno-Oncology Pharma Congress, Boston] Press Release

BeiGene and SpringWorks Therapeutics Announce the Formation of MapKure to Develop BGB-3245, an Investigational, Selective Next-Generation RAF Kinase Inhibitor

MapKure intends to develop BGB-3245, an investigational, oral, selective small molecule inhibitor of monomer and dimer forms of activating B-RAF mutations including V600 BRAF mutations, non-V600 B-RAF mutations, and RAF fusions. These mutations and fusions have been identified in a number of solid tumors to be drivers of cancer growth, including in non-small cell lung cancer, colorectal cancer, thyroid cancer, and brain tumors. [SpringWorks Therapeutics, Inc.] Press Release

Tolero Pharmaceuticals Announces First Patient Dosed with Investigational Agent TP-0903 in Phase I/II Study in Patients with Previously Treated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Tolero Pharmaceuticals, Inc. announced that the first patient has been dosed in a Phase I/II study evaluating the investigational agent TP-0903, an AXL receptor tyrosine kinase inhibitor, in patients with previously treated chronic lymphocytic leukemia and small lymphocytic lymphoma. [Tolero Pharmaceuticals, Inc.] Press Release

Regorafenib to Be Tested in Brain Cancer Patients in Multi-Arm Cooperation Trial

Bayer announced that the regorafenib arm of the platform trial “GBM AGILE” opened for enrollment in the US for patients with newly diagnosed and recurrent glioblastoma (GBM), the most aggressive and common form of primary brain cancer. This marks the start of an international, innovative study with a seamless Phase II/III design set up to rapidly identify effective therapies for patients with GBM; sponsored by the Global Coalition for Adaptive Research, with Bayer supporting the trial with drug supply and grants. [Bayer AG] Press Release

Daiichi Sankyo’s VANFLYTA^® Receives Approval in Japan for the Treatment of Relapsed/Refractory FLT3-ITD AML

Daiichi Sankyo Company, Limited announced that the Ministry of Health, Labor and Welfare (MHLW) of Japan has approved VANFLYTA^®, an oral FLT3 inhibitor, for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML), as detected by an MHLW-approved test. [Daiichi Sankyo Company, Limited] Press Release

Japan Becomes the First Country to Approve Roche’s Personalised Medicine Rozlytrek

Roche announced that Japan’s Ministry of Health, Labour and Welfare has approved Rozlytrek^® for the treatment of adult and paediatric patients with neurotrophic tyrosine receptor kinase fusion-positive, advanced recurrent solid tumors. [F. Hoffmann-La Roche Ltd] Press Release

Beactica Wins Grant to Develop Combination Therapy for Glioblastoma

Beactica AB announced that it has been awarded a grant of 2.8 million Swedish Krona from SweLife and Medtech4Health for its project focused on finding effective therapies for glioblastoma, an aggressive form of brain cancer. The compound developed by Beactica, BEA-17, recently showed indication of efficacy in an in vivo proof-of-principle study. [Beactica AB] Press Release

Mill Creek Life Sciences Receives Grant from Regenerative Medicine Minnesota for Development of Dendritic Cell Vaccine

Mill Creek Life Sciences, LLC. has received a one-year $100,000 grant from Regenerative Medicine Minnesota titled: “Development of Technology for the Large-scale Production of a Novel Dendritic Cell Vaccine for the Treatment of Glioblastoma.” [Mill Creek Life Sciences, LLC. (PR Newswire Association LLC.)] Press Release

Africa’s Science Academy Leads Push for Ethical Data Use

The African Academy of Sciences has started work on the continent’s first cross-disciplinary guidelines on how to collect, store and share research data and specimens in ways that protect study participants from exploitation and benefit African citizens. [Nature News] Editorial

Trump Issues Executive Order that Could Reduce Scientific Advice

President Donald Trump issued an executive order on June 14 to cut back the number of advisory committees by at least a third by the end of September, according to a statement from the White House. The federal advisory committee system is the formal structure for government agencies to seek advice from experts including scientists. [The Scientist] Editorial

China Announces Hefty Fines for Unauthorized Collection of DNA

China announced a new law restricting the collection and use of genetic resources from people in the country — including biological samples that yield DNA, such as blood, and data gleaned from sequencing them. There will be hefty fines for unauthorized collection or use of genetic material. [Nature News] Editorial

NEW 5^th CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
September 25-28, 2019
Paris, France

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

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

NEW 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)

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)

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