EGFR/FOXO3a/BIM signaling pathway determines chemosensitivity of BMP4-differentiated glioma stem cells to temozolomide

Abstract

Brain cancer: Stem cell properties may determine chemotherapy success The properties of individual glioma stem cells (GSCs) may influence the success of chemotherapy in tackling aggressive brain cancer. GSCs promote tumor growth and chemotherapy resistance in glioblastoma tumors. One potential treatment approach uses bone morphogenetic proteins to induce GSCs to differentiate into less harmful cells. Once the GSC population has dwindled, chemoresistance reduces in many but not all cases. Jakub Mieczkowski, Bozena Kaminska and co-workers at the Nencki Institute of Experimental Biology in Warsaw, Poland, conducted experiments on patient-derived glioblastoma cell cultures. They found that samples with high expression levels of the epidermal growth factor receptor (EGFR) protein in GSCs showed heightened sensitivity to the chemotherapy drug temozolomide after differentiation. Conversely, low levels of EGFR resulted in chemoresistance being maintained after differentiation, which may explain the failure of chemotherapy in some patients.