Autophagy in Cancer: Regulation by Small Molecules

Trends Pharmacol Sci. 2018 Dec;39(12):1021-1032. doi: 10.1016/j.tips.2018.10.004.

Abstract

During times of stress, autophagy is a cellular process that enables cells to reclaim damaged components by a controlled recycling pathway. This mechanism for cellular catabolism is dysregulated in cancer, with evidence indicating that cancer cells rely on autophagy in the hypoxic and nutrient-poor microenvironment of solid tumors. Mounting evidence suggests that autophagy has a role in the resistance of tumors to standard-of-care (SOC) therapies. Therefore, there is significant interest in the discovery of small molecules that can safely modulate autophagy. In this review, we describe recent advances in the identification of new pharmacological compounds that modulate autophagy, with a focus on their mode of action, value as probe compounds, and validation as potential therapeutics.

Keywords: autophagosome; autophagy; cancer; kinase; oncology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Autophagy / drug effects*
  • Autophagy-Related Proteins / antagonists & inhibitors
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Antineoplastic Agents
  • Autophagy-Related Proteins
  • Protein Kinase Inhibitors