Epigenetic modulation in cancer drug discovery: promising targets and clinical applications

Epigenetic modulation has emerged as a central strategy that can change the fate of tumour cells to offer more rational and precise approaches by modulating reversible changes in chromatin structure, regulating gene expression without altering DNA sequence. Many reports have indicated the contributions of abnormal epigenetic alterations, particularly DNA methylation and histone modification patterns, as well as their association with non-coding RNA interactions during cancer emergence, development or resistance to standard therapies. Ongoing studies on various inhibitors also demonstrate encouraging preclinical results and potent inhibitory activity. Furthermore, combining epigenetic medicines with conventional treatment approaches such as chemotherapy and radiotherapy is proven to improve therapeutic efficacy in resistant cases of various malignancies. This article also briefly reviews RNA modifications (epitranscriptomics, such as m6A and m5C), novel acetylation modifications, chromosomal interaction studies, and the role of AlphaFold. The present review further illustrates these translational challenges and future opportunities in epigenetic drug development, while shedding light on the necessity of developing predictive biomarkers capable of informing personalized therapies to reduce off-target effects. The ability to target epigenetic modulators has the potential to improve patient outcomes and increase treatment options when coupled with traditional guidelines, as evidenced by on-going clinical trials and FDA approvals.