Advances in the Delivery and Development of Epigenetic Therapeutics for the Treatment of Cancer

Gene expression at the transcriptional level is altered by epigenetic modifications such as DNA methylation, histone methylation, and acetylation, which can upregulate, downregulate, or entirely silence genes. Pathological dysregulation of epigenetic processes can result in the development of cancer, neurological problems, metabolic disorders, and cardiovascular diseases. It is of promising therapeutic interest to find medications that target these epigenetic alterations. Despite the enormous amount of work that has been done in this area, very few molecules have been approved for clinical purposes. This article provides a comprehensive review of recent advances in epigenetic therapeutics for cancer, with a specific focus on emerging delivery and development strategies. Various delivery systems, including pro-drugs, conjugated molecules, nanoparticles (NPs), and liposomes, as well as remedial strategies such as combination therapies, and epigenetic editing, are being investigated to improve the efficacy and specificity of epigenetic drugs (epi-drugs). Furthermore, the challenges associated with available epi-drugs and the limitations of their translation into clinics have been discussed. Target selection, isoform selectivity, physiochemical properties of synthesized molecules, drug screening, and scalability of epi-drugs from preclinical to clinical fields are the major shortcomings that are addressed. This Review discusses novel strategies for the identification of new biomarkers, exploration of the medicinal chemistry of epigenetic modifiers, optimization of the dosage regimen, and design of proper clinical trials that will lead to better utilization of epigenetic modifiers over conventional therapies. The integration of these approaches holds great potential for improving the efficacy and precision of epigenetic treatments, ultimately benefiting cancer patients.