Targeting mitophagy to overcome chemoresistance in ovarian and brain cancers

In Oncology, chemoresistance is often responsible for therapeutic failure. In this work where we used human cancer models, we investigated whether precise metabolic changes could account for chemoresistance. Not only in cisplatin-resistant ovarian cancer but also in temozolomide-resistant glioblastoma, we evidenced highly oxidative chemoresistant phenotypes depending on mitophagy. Consequently, inhibiting either mitophagy by more largely blocking autophagy or cell respiration by targeting Complex I in the electron transport chain with olaparib allowed to resensitize cancer cells to cisplatin and/or to temozolomide. We propose that these two approaches used in combination therapies with selected forms of chemotherapy would be attractive for countering cancer chemoresistance.
(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022