Hypomethylating Agents and Epigenetic Biomarkers: Reprogramming Methylation Patterns in Cancer Therapy.

Abstract

A total of 1,487 records were identified, of which 42 studies met the inclusion criteria. Hypomethylating agents, particularly azacitidine and decitabine, demonstrated therapeutic efficacy in hematologic malignancies and showed growing potential in selected solid tumors. Epigenetic biomarkers were found to be valuable for predicting treatment response, monitoring disease progression, and identifying patients most likely to benefit from methylation-targeted therapies. Combined approaches integrating hypomethylating agents with immunotherapy, targeted therapy, or chemotherapy further enhanced antitumor activity in several clinical settings. A systematic review was conducted in accordance with PRISMA guidelines. Electronic databases including PubMed, Scopus, Web of Science, and the Cochrane Library were searched for studies published between January 2014 and December 2025. Studies evaluating hypomethylating agents, DNA methylation biomarkers, and their clinical relevance in cancer diagnosis, prognosis, and treatment were included. Epigenetic dysregulation, particularly aberrant DNA methylation, plays a central role in cancer initiation, progression, and therapeutic resistance.