Targeting DNA methyltransferases in non-small-cell lung cancer

Semin Cancer Biol. 2022 Aug;83:77-87. doi: 10.1016/j.semcancer.2021.01.005. Epub 2021 Jan 21.


Despite the advances in treatment using chemotherapy or targeted therapies, due to static survival rates, non-small cell lung cancer (NSCLC) is the major cause of cancer-related deaths worldwide. Epigenetic-based therapies have been developed for NSCLC by targeting DNA methyltransferases (DNMTs) and histone-modifying enzymes. However, treatment using single epigenetic agents on solid tumours has been inadequate; whereas, treatment with a combination of DNMTs inhibitors with chemotherapy and immunotherapy has shown great promise. Dietary sources of phytochemicals could also inhibit DNMTs and cancer stem cells, representing a novel and promising way to prevent and treat cancer. Herein, we will discuss the different DNMTs, DNA methylation profiling in NSCLC as well as current demethylating agents in ongoing clinical trials. Therefore, providing a concise overview of future developments in the field of epigenetic therapy in NSCLC.

Keywords: DNA methylation; DNA methyltransferases; Demethylating agents; Dietary phytochemicals; Non-small cell lung cancer.

Publication types

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

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • DNA
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • Epigenesis, Genetic
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics


  • Antineoplastic Agents
  • DNA
  • DNA Modification Methylases