Targeting epigenetic regulators to overcome drug resistance in cancers

• Published in: Signal transduction and targeted therapy Vol. 8; no. 1; pp. 69 - 24
• Main Authors: Wang, Nan, Ma, Ting, Yu, Bin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.02.2023; Nature Publishing Group
• Subjects: 631/154; 631/92; Cancer Research; Cell Biology; DNA methylation; Drug Resistance; Epigenesis, Genetic - genetics; Epigenetics; Histone Demethylases - genetics; Histones; Histones - genetics; Humans; Internal Medicine; Jumonji Domain-Containing Histone Demethylases - genetics; Jumonji Domain-Containing Histone Demethylases - metabolism; Medicine; Medicine & Public Health; Neoplasms - drug therapy; Neoplasms - genetics; Nucleotide sequence; Oncology; Pathology; Review; Review Article; RNA modification; siRNA; Tumors
• ISSN: 2059-3635; 2095-9907; 2059-3635
• DOI: 10.1038/s41392-023-01341-7

Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic regulation mechanisms, DNA methylation, histone modification, and non-coding RNA regulation have been well studied. Increasing evidence has shown that aberrant epigenetic regulations contribute to tumor resistance. Therefore, targeting epigenetic regulators represents an effective strategy to reverse drug resistance. In this review, we mainly summarize the roles of epigenetic regulation in tumor resistance. In addition, as the essential factors for epigenetic modifications, histone demethylases mediate the histone or genomic DNA modifications. Herein, we comprehensively describe the functions of the histone demethylase family including the lysine-specific demethylase family, the Jumonji C-domain-containing demethylase family, and the histone arginine demethylase family, and fully discuss their regulatory mechanisms related to cancer drug resistance. In addition, therapeutic strategies, including small-molecule inhibitors and small interfering RNA targeting histone demethylases to overcome drug resistance, are also described.