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Review
. 2023 Jan 11;15(1):6.
doi: 10.1186/s13148-022-01419-z.

Drugging the epigenome in the age of precision medicine

Taylor Feehley  1 , Charles W O'Donnell  1 , John Mendlein  2 , Mahesh Karande  1 , Thomas McCauley  3
Affiliations
Review

Drugging the epigenome in the age of precision medicine

Taylor Feehley et al. Clin Epigenetics. .

Abstract

Background: Modulating the epigenome has long been considered a potential opportunity for therapeutic intervention in numerous disease areas with several approved therapies marketed, primarily for cancer. Despite the overall promise of early approaches, however, these drugs have been plagued by poor pharmacokinetic and safety/tolerability profiles due in large part to off-target effects and a lack of specificity.

Results: Recently, there has been marked progress in the field on a new generation of epigenomic therapies which address these challenges directly by targeting defined loci with highly precise, durable, and tunable approaches. Here, we review the promise and pitfalls of epigenetic drug development to date and provide an outlook on recent advances and their promise for future therapeutic applications.

Conclusions: Novel therapeutic modalities leveraging epigenetics and epigenomics with increased precision are well positioned to advance the field and treat patients across disease areas in the coming years.

Keywords: Epigenetics; Epigenomics; Precision; Specificity; Therapeutics.

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Conflict of interest statement

TF, CWO, MK, and TM are employees of Omega Therapeutics, and that JM is an employee of Flagship Pioneering and a member of the Board of Directors of Omega Therapeutics.

Figures

Fig. 1
Fig. 1
Precision epigenomic therapies have the potential to improve efficacy and tolerability. Early epigenomic therapies are limited by a lack of specificity, leading to off-target effects and more narrow therapeutic utility, as well as more limited tunability and durability. Precision therapies that act at discrete, specific loci should mitigate these challenges while delivering on the therapeutic promise of epigenomic modulation
Fig. 2
Fig. 2
The evolution of epigenetic and epigenomic therapies. The first epigenetic therapeutics were first discovered in the 1960s but the first approval did not come until the early 2000s. Development in the field has accelerated markedly over the past 20 years, with epigenomic programming being the most recent advance. Green = DNMT inhibitor milestones; orange = HDAC inhibitor milestones; purple = 3rd generation epigenetic therapeutic milestones; blue = epigenomic programming milestones
See this image and copyright information in PMC

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