Targeting the c-Met/FZD8 Signaling Axis Eliminates Patient-Derived Cancer Stem-Like Cells in Head and Neck Squamous Carcinomas Scientists report that silencing c-Met is sufficient to suppress sphere formation, tumor initiation and metastatic properties of head and neck-cancer stem-like cells (CSC). Pharmacologic inhibition of c-Met with the selective inhibitor PF-2341066 preferentially targeted CSC and synergized with conventional chemotherapy to improve efficacy in a mouse xenograft model of head and neck squamous carcinomas, impeding tumor growth and reducing metastasis. [Cancer Res] Abstract | Full Article DNMT-Dependent Suppression of MicroRNA Regulates the Induction of GBM Tumor-Propagating Phenotype by Oct4 and Sox2 Researchers show that the reprogramming transcription factors Oct4 and Sox2 induce glioblastoma (GBM) cells to become stem-like and tumor-propagating via a mechanism involving direct DNA methyl transferase (DNMT) promoter transactivation, resulting in global DNA methylation- and DNMT-dependent downregulation of multiple microRNAs. [Oncogene] Abstract A Phase I Dose Escalation and Expansion Study of the Anti-Cancer Stem Cell Agent Demcizumab (Anti-DLL4) in Patients with Previously Treated Solid Tumors This Phase I trial evaluated the safety, pharmacokinetics, pharmacodynamics and of demcizumab, a humanized IgG2 monoclonal antibody targeting the Notch ligand DLL4 in adult patients with advanced malignancies. [Clin Cancer Res] Abstract | Full Article Dual mTORC1/2 Blockade Inhibits Glioblastoma Brain Tumor Initiating Cells In Vitro and In Vivo and Synergizes with Temozolomide to Increase Orthotopic Xenograft Survival Human brain tumor-initiating cell lines with different combinations of endogenous EGFR wild-type, EGFRvIII, and PTEN mutations were used to investigate response to the EGFR inhibitor gefitinib, mTORC1 inhibitor rapamycin, and dual mTORC1/2 inhibitor AZD8055 alone and in combination with temozolomide. [Clin Cancer Res] Abstract SPARC Mediates Metastatic Cooperation between CSC and Non-CSC Prostate Cancer Cell Subpopulations Cancer stem cell (CSC)-enriched subpopulation (M) and non-CSC subpopulation (S) secretomes were compared by stable isotope labeling by amino acids in cell culture. Comparative secretome analysis yielded 213 proteins differentially secreted between M and S cells. [Mol Cancer] Abstract | Full Article CXCL12/CXCR4 Blockade by Oncolytic Virotherapy Inhibits Ovarian Cancer Growth by Decreasing Immunosuppression and Targeting Cancer-Initiating Cells Scientists investigated the antitumor efficacy of a CXCR4 antagonist expressed by oncolytic vaccinia virus against an invasive variant of the murine epithelial ovarian cancer cell line ID8-T. This variant harbors a high frequency of cancer-initiating cells that form multilayered spheroid cells and express the hyaluronan receptor CD44, as well as stem cell factor receptor CD117. [J Immunol] Abstract SOX2 Regulates Self-Renewal and Tumorigenicity of Stem-Like Cells of Head and Neck Squamous Cell Carcinoma Researchers created cells ectopically expressing sex-determining region Y-box (SOX2) from previously established head and neck squamous cell carcinomas (HNSCC) cells and examined the cell proliferation, self-renewal capacity, and chemoresistance of these cells compared with control cells. In addition, they knocked down SOX2 in primary spheres obtained from HNSCC tumor tissue and assessed the attenuation of stemness-associated traits in these cells in vitro and in vivo. [Br J Cancer] Abstract Fibroblasts Induce Expression of FGF4 in Ovarian Cancer Stem-Like Cells/Cancer-Initiating Cells and Upregulate Their Tumor Initiation Capacity Researchers investigated the effects of fibroblasts on tumor-initiating capacity and stem-like properties of ovarian cancer stem-like cells (CSCs)/cancer-initiating cells (CICs). CSCs/CICs were isolated from the ovarian carcinoma cell line HTBoA as aldehyde dehydrogenase 1 high population by the ALDEFLUOR assay. [Lab Invest] Abstract Impairment of Lysosomal Activity as a Therapeutic Modality Targeting Cancer Stem Cells of Embryonal Rhabdomyosarcoma Cell Line RD Scientists isolated rhabdomyosarcoma cancer stem cells (CSC) with stem-like features. Rhabdomyosarcoma CSC showed higher invasive ability and a reduced cytotoxicity to doxorubicin in comparison to native cells, through a mechanism unrelated to the classical multidrug resistance process. [PLoS One] Full Article Chaetocin Antileukemia Activity against Chronic Myelogenous Leukemia Cells Is Potentiated by Bone Marrow Stromal Factors and Overcomes Innate Imatinib Resistance Bone marrow stromal cytokines and growth factors did not inhibit imatinib activities when TonB210 cells expressing Bcr-Abl were cotreated with chaetocin. Chaetocin showed similar activities against leukemic stem cells-enriched chronic myelogenous leukemia (CML) cell populations isolated from a murine transplant model of CML blast crisis that were phenotypically negative for lineage markers and positive for Sca-1 and c-Kit. [Oncogenesis] Full Article  |