Luca X Zampieri, Martina Sboarina, Andrea Cacace, Debora Grasso, Léopold Thabault, Loïc Hamelin, Thibaut Vazeille, Elodie Dumon, Rodrigue Rossignol, Raphaël Frédérick, Etienne Sonveaux, Florence Lefranc, Pierre Sonveaux
Glioblastoma represents the highest grade of brain tumors. Despite maximal resection surgery associated with radiotherapy and concomitant followed by adjuvant chemotherapy with temozolomide (TMZ), patients have a very poor prognosis due to the rapid recurrence and the acquisition of resistance to TMZ. Here, initially considering that TMZ is a prodrug whose activation is pH-dependent, we explored the contribution of glioblastoma cell metabolism to TMZ resistance. Using isogenic TMZ-sensitive and TMZ-resistant human glioblastoma cells, we report that the expression of O6-methylguanine DNA methyltransferase (MGMT), which is known to repair TMZ-induced DNA methylation, does not primarily account for TMZ resistance...
November 3, 2021: International Journal of Molecular Sciences