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Review
. 2025 Feb 26;44(1):37.
doi: 10.1007/s10555-025-10253-7.

Epigenetic drugs in cancer therapy

Amila Suraweera  1 , Kenneth J O'Byrne  2   3 , Derek J Richard  2
Affiliations
Review

Epigenetic drugs in cancer therapy

Amila Suraweera et al. Cancer Metastasis Rev. .

Abstract

Genetic and epigenetic modifications of DNA are involved in cancer initiation and progression. Epigenetic modifications change chromatin structure and DNA accessibility and thus affect DNA replication, DNA repair and transcription. Epigenetic modifications are reversible and include DNA methylation, histone acetylation and histone methylation. DNA methylation is catalysed by DNA methyltransferases, histone acetylation and deacetylation are catalysed by histone acetylases and deacetylases, while histone methylation is catalysed by histone methyltransferases. Epigenetic modifications are dysregulated in several cancers, making them cancer therapeutic targets. Epigenetic drugs (epi-drugs) which are inhibitors of epigenetic modifications and include DNA methyltransferase inhibitors (DNMTi), histone deacetylase inhibitors (HDACi), histone methyltransferase inhibitors (HMTi) and bromodomain and extra-terminal motif protein inhibitors (BETi), have demonstrated clinical success as anti-cancer agents. Furthermore, the combination of epi-drugs with standard chemotherapeutic agents has demonstrated promising anti-cancer effects in pre-clinical and clinical settings. In this review, we discuss the role of epi-drugs in cancer therapy and explore their current and future use in combination with other anti-cancer agents used in the clinic. We further highlight the side effects and limitations of epi-drugs. We additionally discuss novel delivery methods and novel tumour epigenetic biomarkers for the screening, diagnosis and development of personalised cancer treatments, in order to reduce off-target toxicity and improve the specificity and anti-tumour efficacy of epi-drugs.

Keywords: Cancer therapy; DNA methyltransferase inhibitors; Epigenetic drugs; Histone deacetylase inhibitors; Histone methyltransferase inhibitors.

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Conflict of interest statement

Declarations. Competing interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
A schematic illustration depicting the role of DNA methyltransferases (DNMT), histone demethylases (HDM), histone methyltransferase (HMT), histone acetyltransferases (HAT) and histone deacetylases (HDAC), and names and mechanism of action of FDA approved DNA methyltransferase inhibitors (DNMTi), histone methyltransferase inhibitors (HMTi) and histone deacetylase inhibitors (HDACi)
See this image and copyright information in PMC

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