Monique Courtade-Saîdi and Solène Evrard
Glioblastoma stem cells (GSCs) are implicated in the aggressiveness and recurrence of glioblastoma. This team has shown that GSCs can transdifferentiate into cells with endothelial characteristics (called TDECs) and that irradiation potentiates the pro-angiogenic functions of these TDECs. Thus, these TDECs could also participate in the formation of new vessels essential for tumour cells, particularly in residual tumours and during recurrence after irradiation. The Tie2 signalling pathway has been implicated in this mechanism (Deshors P et al. Cell Death Dis 2019;10:816), thus opening the way to new therapeutic approaches. In addition, a transcriptomic study has identified other pathways potentially involved in this transdifferentiation. Within the framework of this project, inhibitors of these pathways are now being studied in vitro and in vivo with a view to their transfer to the clinic.
The research will focus on the impact of this transdifferentiation during tumour development in orthotopic xenograft models. In parallel, the signalling pathways corresponding to the potentially involved molecules that have been identified will be explored. It will thus be possible to test the effect of more specific pharmacological inhibitors of this angiogenic pathway and their potentiation by irradiation.