Abstract 7204: Therapeutic potential of targeting autophagy to overcome chemoresistance in glioblastoma

Abstract Glioblastoma (GBM) is the most malignant subtype of brain tumor in adults, characterized by relentless recurrence and an overall survival of approximately 18 months. Temozolomide (TMZ) has been the basis for current standard of care and represents the control-arm in GBM trials. Despite the use of TMZ having shown promising results in improving patient survival, drug resistance and tumor relapse is almost inevitable. Current literature has provided strong evidence on autophagy modulation as an adjuvant therapy to cytotoxic treatments. By using in vitro and in vivo GBM models, combination regimen with TMZ and an autophagy activator significantly enhanced the cytotoxic effect in tumors that were resistant to chemotherapy. Combined treatment readily induced a mortal autophagy flux in chemo-resistant GBM cells resulted from its high intrinsic autophagy. Our findings suggest that treatment resistant tumors are more sensitive to autophagy activation when compared to treatment-naive tumors. As they often exhibit higher basal level of autophagy after long-term chemotherapy, a mortal autophagy flux can be readily achieved. In conclusion, combination therapy of a cytotoxic drug with autophagy modulator is emerging as a novel therapeutic strategy in the adjuvant setting for cancer patients. Citation Format: Karrie Mei Yee Kiang, Gilberto Ka Kit Leung. Therapeutic potential of targeting autophagy to overcome chemoresistance in glioblastoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 7204.