Epigenetic enzyme inhibitors targeting DNA, histone, and RNA methylation: Mechanisms and therapeutic applications in cancer.

Epigenetic modifications, such as DNA methylation, histone methylation, and RNA methylation, dynamically regulate gene transcription and play critical roles in cellular differentiation, development, and disease, especially cancer. Inhibitors targeting the enzymes responsible for these modifications have emerged as promising cancer therapies. For instance, DNMT inhibitors (e.g., azacitidine, decitabine) can reactivate tumor suppressor genes via demethylation; HMT inhibitors like tazemetostat and EPZ-5676 modulate chromatin structure to exert anti-tumor effects; and RNA methyltransferase inhibitors such as STM2457 disrupt RNA metabolism to suppress tumor growth. Despite encouraging preclinical and clinical results, challenges including toxicity and drug resistance remain obstacles to broader clinical application. This review summarizes recent advances in epigenetic inhibitor development to support the design of safer and more effective targeted cancer therapies.