Abstract
Autophagy is a process essential for cellular energy consumption, survival, and defense mechanisms. The role of autophagy in several types of human cancers has been explicitly explained; however, the underlying molecular mechanism of autophagy in glioblastoma remains ambiguous. Autophagy is thought to be a “double-edged sword”, and its effect on tumorigenesis varies with cell type. On the other hand, autophagy may play a significant role in the resistance mechanisms against various therapies. Therefore, it is of the utmost importance to gain insight into the molecular mechanisms deriving the autophagy-mediated therapeutic resistance and designing improved treatment strategies for glioblastoma. In this review, we discuss autophagy mechanisms, specifically its pro-survival and growth-suppressing mechanisms in glioblastomas. In addition, we try to shed some light on the autophagy-mediated activation of the cellular mechanisms supporting radioresistance and chemoresistance in glioblastoma. This review also highlights autophagy’s involvement in glioma stem cell behavior, underlining its role as a potential molecular target for therapeutic interventions.
Highlights
Introduction published maps and institutional affilGliomas are the primary tumors of the central nervous system (CNS), which displays highly heterogeneous features
epidermal growth factor (EGFR) is recognized as a driving receptor tyrosine kinase (RTK) in glioblastoma and induces multiple oncogenic signaling, which accounts for approximately 60% of glioblastoma cases [14]
Our study suggests that some glioma stem cells (GSC), including those isolated from patients, showed a decreased or increased expression of Beclin 1 in comparison with normal astrocytes [203]
Summary
The cells to to avoid avoidcell celldeath deathininthe thepresence presenceofofchemotherapeutics chemotherapeuticsis is knownasaschemoresistance. Co-treatment with CQ and bevacizumab, which are known autophagy inhibitors, reduced the growth of tumor These experimental findings reveal a unique means of resistance to anti-angiogenic therapy, where cell survival is promoted by hypoxia-mediated autophagy [23]. Shen et al suggested that implementing small molecule inhibitor ZD6474 (Vandetanib) could induce autophagy in glioma cells to overcome the cytoprotective adaptive response against chemotherapy [134] Their findings suggested ZD6474 induced autophagy in U251 and U87 cells, mediated through the PI3K/Akt/mTOR signaling pathways. NVP-BEZ235 in combination with CQ inhibited autophagy and induced a reduction in tumor growth in vivo [135] These findings describe the potential of inhibiting the PI3K/mTOR pathway to target autophagy-mediated chemoresistance in glioblastomas. These finding indicated the importance of CASC2 lncRNA as a potential therapeutic target for therapeutic intervention [137]
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