A Novel Combination Therapy Approach Targeting STAT3 and Autophagy in Glioblastoma

Abstract

The aggressive brain cancer glioblastoma (GBM) is notoriously resistant to radiotherapy and chemotherapy, which drives tumor recurrence and relapse. GBM cells are highly addicted to STAT3 (signal transducer and activator of transcription 3) and STAT3 inhibition blocks GBM-driven tumor growth. STAT3 regulates macroautophagy/autophagy, a central player in GBM pathobiology. Although autophagy suppression has been implicated in the pathophysiology of GBM, it is unknown if modulation of autophagy can reduce GBM tumorigenesis. Based on observations from our recent study, the answer appears to be yes, and we propose a therapeutic strategy for dual inhibition of STAT3 and MTOR, or STAT3 and ULK1 to target GBM tumorigenesis and chemoresistance.

Keywords

• ampkα
• apoptosis
• caspase 3
• cathepsin d
• lc3-i/lc3-ii
• mtorc1
• rad001 (everolimus)
• ulk1