Cytotoxic autophagy in cancer therapy

Int J Mol Sci. 2014 Jun 5;15(6):10034-51. doi: 10.3390/ijms150610034.

Abstract

Autophagy is a process of cellular self-digestion, whereby the cell degrades subcellular materials in order to generate energy and metabolic precursors in order to prolong survival, classically under conditions of nutrient deprivation. Autophagy can also involve the degradation of damaged or aged organelles, and misfolded or damaged proteins to eliminate these components that might otherwise be deleterious to cellular survival. Consequently, autophagy has generally been considered a prosurvival response. Many, if not most chemotherapeutic drugs and radiation also promote autophagy, which is generally considered a cytoprotective response, in that its inhibition frequently promotes apoptotic cells death. Furthermore, it has been shown that conventional chemotherapeutic drugs and radiation alone rarely induce a form of autophagy that leads to cell death. However, there are multiple examples in the literature where newer chemotherapeutic agents, drug combinations or drugs in combination with radiation promote autophagic cell death. This review will describe autophagic cell death induced in breast tumor cells, lung cancer cells as well as glioblastoma, demonstrating that it cannot be concluded that stress induced autophagy is, of necessity, cytoprotective in function.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Autophagy* / drug effects
  • Autophagy* / radiation effects
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology*
  • Brain / radiation effects
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / radiotherapy
  • Breast / drug effects
  • Breast / metabolism
  • Breast / pathology
  • Breast / radiation effects
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / radiotherapy
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Glioblastoma / radiotherapy
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung / radiation effects
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / radiotherapy

Substances

  • Antineoplastic Agents