Deciphering the Role of Autophagy in Treatment of Resistance Mechanisms in Glioblastoma

Int J Mol Sci. 2021 Jan 28;22(3):1318. doi: 10.3390/ijms22031318.

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.

Keywords: autophagy; chemoresistance; glioblastoma; glioma stem cells; molecular targets; radioresistance.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Autophagy
  • Autophagy-Related Proteins / metabolism*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / radiotherapy
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism*
  • Glioblastoma / radiotherapy
  • Humans
  • Radiation Tolerance*
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Autophagy-Related Proteins