Epigenetic Pharmacology in Precision Oncology: DNA Methyltransferase and Histone-Targeting Therapies from Molecular Mechanisms to Clinical Translation — A Narrative Review
DOI:
https://doi.org/10.68041/medsc.v1i1/03Keywords:
Chromatin Assembly and Disassembly, DNA Methylation, Epigenomics, Histone Deacetylase Inhibitors, Molecular Targeted Therapy, Neoplasms, Precision MedicineAbstract
Epigenetic changes contribute to cancer initiation, progression, and therapeutic resistance, as they control the expression of genes without affecting their DNA sequence. Epigenetic regulators are potential targets for precision oncology as they are involved in the progression of tumors, immune escape, and resistance to therapy, all of which are associated with aberrant DNA methylation and chromatin modifications. DNA methyltransferase (DNMT) inhibitors and histone-targeting drugs like histone deacetylase (HDAC) inhibitors have been clinically beneficial, particularly in hematological malignancies. However, they have a limited number of drawbacks, such as lack of specificity, toxicity, resistance, and lack of predictive biomarkers. With recent developments in multi-omics profiling, single-cell epigenomics, and targeted epigenome editing, more personalized therapeutic strategies are becoming a reality. This narrative review outlines the molecular mechanisms, clinical applications, and drawbacks in the use of DNA methyltransferase and histone-targeting therapies, and introduces novel strategies for patient selection based on biomarkers and for combination therapy. The combination of epigenomic technologies and precision medicine strategies could enable more effective therapeutic strategies and help develop more targeted, more durable types of cancer therapies.
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