Autophagy modulating agents as chemosensitizers for cisplatin therapy in cancer

Invest New Drugs. 2021 Apr;39(2):538-563. doi: 10.1007/s10637-020-01032-y. Epub 2020 Nov 7.

Abstract

Although cisplatin is one of the most common antineoplastic drug, its successful utilisation in cancer treatment is limited by the drug resistance. Multiple attempts have been made to find potential cisplatin chemosensitisers which would overcome cancer cells resistance thus improving antineoplastic efficacy. Autophagy modulation has become an important area of interest regarding the aforementioned topic. Autophagy is a highly conservative cellular self-digestive process implicated in response to multiple environmental stressors. The high basal level of autophagy is a common phenomenon in cisplatin-resistant cancer cells which is thought to grant survival benefit. However current evidence supports the role of autophagy in either promoting or limiting carcinogenesis depending on the context. This encourages the search of substances modulating the process to alleviate cisplatin resistance. Such a strategy encompasses not only simple autophagy inhibition but also harnessing the process to induce autophagy-dependent cell death. In this paper, we briefly describe the mechanism of cisplatin resistance with a special emphasis on autophagy and we give an extensive literature review of potential substances with cisplatin chemosensitising properties related to autophagy modulation.

Keywords: Autophagy; Cancer resistance; Cisplatin; Combination therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Autophagic Cell Death / drug effects
  • Autophagic Cell Death / physiology
  • Autophagy / drug effects*
  • Autophagy / physiology*
  • Cell Survival / physiology
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Epigenesis, Genetic / physiology
  • Humans
  • Lysosomes / drug effects
  • Lysosomes / physiology
  • Neoplasms / drug therapy

Substances

  • Antineoplastic Agents
  • Cisplatin