Therapeutic targeting of DNA methylation alterations in cancer
Document Type
Journal Article
Publication Date
4-1-2024
Journal
Pharmacology & therapeutics
Volume
258
DOI
10.1016/j.pharmthera.2024.108640
Keywords
Cancer; DNA methylation; DNMT inhibitor, epigenetic
Abstract
DNA methylation is a critical component of gene regulation and plays an important role in the development of cancer. Hypermethylation of tumor suppressor genes and silencing of DNA repair pathways facilitate uncontrolled cell growth and synergize with oncogenic mutations to perpetuate cancer phenotypes. Additionally, aberrant DNA methylation hinders immune responses crucial for antitumor immunity. Thus, inhibiting dysregulated DNA methylation is a promising cancer therapy. Pharmacologic inhibition of DNA methylation reactivates silenced tumor suppressors and bolster immune responses through induction of viral mimicry. Now, with the advent of immunotherapies and discovery of the immune-modulatory effects of DNA methylation inhibitors, there is great interest in understanding how targeting DNA methylation in combination with other therapies can enhance antitumor immunity. Here, we describe the role of aberrant DNA methylation in cancer and mechanisms by which it promotes tumorigenesis and modulates immune responses. Finally, we review the initial discoveries and ongoing efforts to target DNA methylation as a cancer therapeutic.
APA Citation
Lee, Abigail V.; Nestler, Kevin A.; and Chiappinelli, Katherine B., "Therapeutic targeting of DNA methylation alterations in cancer" (2024). GW Authored Works. Paper 4794.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4794
Department
Microbiology, Immunology, and Tropical Medicine