Epigenetic modifications: Key players in cancer heterogeneity and drug resistance

Transl Oncol. 2024 Jan:39:101821. doi: 10.1016/j.tranon.2023.101821. Epub 2023 Nov 4.

Abstract

Cancer heterogeneity and drug resistance remain pivotal obstacles in effective cancer treatment and management. One major contributor to these challenges is epigenetic modifications - gene regulation that does not involve changes to the DNA sequence itself but significantly impacts gene expression. As we elucidate these phenomena, we underscore the pivotal role of epigenetic modifications in regulating gene expression, contributing to cellular diversity, and driving adaptive changes that can instigate therapeutic resistance. This review dissects essential epigenetic modifications - DNA methylation, histone modifications, and chromatin remodeling - illustrating their significant yet complex contributions to cancer biology. While these changes offer potential avenues for therapeutic intervention due to their reversible nature, the interplay of epigenetic and genetic changes in cancer cells presents unique challenges that must be addressed to harness their full potential. By critically analyzing the current research landscape, we identify knowledge gaps and propose future research directions, exploring the potential of epigenetic therapies and discussing the obstacles in translating these concepts into effective treatments. This comprehensive review aims to stimulate further research and aid in developing innovative, patient-centered cancer therapies. Understanding the role of epigenetic modifications in cancer heterogeneity and drug resistance is critical for scientific advancement and paves the way towards improving patient outcomes in the fight against this formidable disease.

Keywords: Cancer heterogeneity; Chromatin remodeling; DNA methylation; Drug resistance; Epigenetic modifications; Epigenetic therapies; Gene expression regulation; Histone modifications.