Cancers, Vol. 11, Pages 359: The Small Molecule Ephrin Receptor Inhibitor, GLPG1790, Reduces Renewal Capabilities of Cancer Stem Cells, Showing Anti-Tumour Efficacy on Preclinical Glioblastoma Models

Cancers, Vol. 11, Pages 359: The Small Molecule Ephrin Receptor Inhibitor, GLPG1790, Reduces Renewal Capabilities of Cancer Stem Cells, Showing Anti-Tumour Efficacy on Preclinical Glioblastoma Models Cancers doi: 10.3390/cancers11030359 Authors: Giovanni Luca Gravina Andrea Mancini Alessandro Colapietro Simona Delle Monache Roberta Sferra Flora Vitale Loredana Cristiano Stefano Martellucci Francesco Marampon Vincenzo Mattei Filip Beirinckx Philippe Pujuguet Laurent Saniere Giocondo Lorenzon Ellen van der Aar Claudio Festuccia Therapies against glioblastoma (GBM) show a high percentage of failure associated with the survival of glioma stem cells (GSCs) that repopulate treated tumours. Forced differentiation of GSCs is a promising new approach in cancer treatment. Erythropoietin-producing hepatocellular (Eph) receptors drive tumourigenicity and stemness in GBM. We tested GLPG1790, a first small molecule with inhibition activity versus inhibitor of various Eph receptor kinases, in preclinical GBM models using in vitro and in vivo assays. GLPG1790 rapidly and persistently inhibited Ephrin-A1-mediated phosphorylation of Tyr588 and Ser897, completely blocking EphA2 receptor signalling. Similarly, this compound blocks the ephrin B2-mediated EphA3 and EphB4 tyrosine phosphorylation. This resulted in anti-glioma effects. GLPG1790 down-modulated the expression of mesenchymal markers CD44, Sox2, nestin, octamer-binding transcription factor 3/4 (Oct3...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research