Targeting autophagy in colorectal cancer: An update on pharmacological small-molecule compounds

Drug Discov Today. 2022 Aug;27(8):2373-2385. doi: 10.1016/j.drudis.2022.05.011. Epub 2022 May 16.

Abstract

Autophagy, an evolutionarily highly conserved cellular degradation process, plays the Janus role (either cytoprotective or death-promoting) in colorectal cancer, so the targeting of several key autophagic pathways with small-molecule compounds may be a new therapeutic strategy. In this review, we discuss autophagy-associated cell death pathways and key cytoprotective autophagy pathways in colorectal cancer. Moreover, we summarize a series of small-molecule compounds that have the potential to modulate autophagy-associated cell death or cytoprotective autophagy for therapeutic purposes. Taken together, these findings demonstrate the Janus role of autophagy in colorectal cancer, and shed new light on the exploitation of a growing number of small-molecule compounds to target autophagy in future cancer drug discovery.

Keywords: Autophagy; Autophagy-associated cell death; Colorectal cancer; Cytoprotective autophagy; Small-molecule compound.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Autophagy
  • Colorectal Neoplasms* / drug therapy
  • Drug Discovery
  • Humans
  • Signal Transduction

Substances

  • Antineoplastic Agents