Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

Immunology. 2020 Mar;159(3):257-278. doi: 10.1111/imm.13160. Epub 2019 Dec 22.

Abstract

Chloroquines are 4-aminoquinoline-based drugs mainly used to treat malaria. At pharmacological concentrations, they have significant effects on tissue homeostasis, targeting diverse signaling pathways in mammalian cells. A key target pathway is autophagy, which regulates macromolecule turnover in the cell. In addition to affecting cellular metabolism and bioenergetic flow equilibrium, autophagy plays a pivotal role at the interface between inflammation and cancer progression. Chloroquines consequently have critical effects in tissue metabolic activity and importantly, in key functions of the immune system. In this article, we will review the work addressing the role of chloroquines in the homeostasis of mammalian tissue, and the potential strengths and weaknesses concerning their use in cancer therapy.

Keywords: Autophagy; chloroquine; drug repurposing; inflammation; lysosome; neoplasm.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Autophagy / drug effects*
  • Chloroquine / adverse effects
  • Chloroquine / therapeutic use*
  • Humans
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Signal Transduction
  • Tumor Hypoxia
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • Inflammation Mediators
  • Chloroquine