The role of drug-metabolizing enzymes in synthetic lethality of cancer

Pharmacol Ther. 2022 Dec:240:108219. doi: 10.1016/j.pharmthera.2022.108219. Epub 2022 May 27.

Abstract

Drug-metabolizing enzymes (DMEs) have shown increasing importance in anticancer therapy. It is not only due to their effect on activation or deactivation of anticancer drugs, but also because of their extensive connections with pathological and biochemistry changes during tumorigenesis. Meanwhile, it has become more accessible to discovery anticancer drugs that selectively targeted cancer cells with the development of synthetic lethal screen technology. Synthetic lethal strategy makes use of unique genetic markers that different cancer cells from normal tissues to discovery anticancer agents. Dysregulation of DMEs has been found in various cancers, making them promising candidates for synthetic lethal strategy. In this review, we will systematically discuss about the role of DMEs in tumor progression, the application of synthetic lethality strategy in drug discovery, and a link between DMEs and synthetic lethal of cancer.

Keywords: Cancer therapy; Drug discovery; Drug metabolizing enzymes (DMEs); Synthetic lethality; Tumor progression.

Publication types

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

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Drug Discovery
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Synthetic Lethal Mutations

Substances

  • dimethylethylsilylimidazole
  • Antineoplastic Agents