# Hallmark (2022): non-mutational epigenetic reprogramming

Source: https://onco.cc/terms/nonmutational-epigenetic-reprogramming/  
OnCo record `nonmutational-epigenetic-reprogramming` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cancers can change behaviour, including becoming drug-tolerant, without any new mutation, by rewriting the chemical tags that control which genes are read.

## Summary

Non-mutational epigenetic reprogramming, a hallmark added in 2022, is the capacity of cancers to change their phenotype, including becoming drug-tolerant, without any new mutation, by rewriting the chemical tags that control which genes are read. It covers drug-tolerant persister states, microenvironment-induced chromatin changes and epigenetic silencing of tumour suppressors and antigens, described in the Epigenetic reprogramming and SWI/SNF chromatin remodelling pathways. The changes are reversible in principle, so Epigenetic drugs (hypomethylating agents, HDAC, EZH2 and BET inhibitors) and epigenetic priming before immunotherapy are the responses, read out by DNA methylation profiling. Readers meet it from the Hallmarks of Cancer overview and the Epigenetic therapy roadmap.

## Fields

- Kind: Term
- Last checked: 2026-09-08
- Tags: hallmark

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer
- Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022): https://doi.org/10.1158/2159-8290.CD-21-1059

## Connected records

- technologies: [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)](https://onco.cc/technologies/epigenetic-drugs/)
- pathways: [Drug-tolerant persister cells](https://onco.cc/pathways/drug-tolerant-persisters/), [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [SWI/SNF chromatin remodelling](https://onco.cc/pathways/swi-snf-chromatin/)
- terms: [Epigenetic progenitor theory: cancer without a first mutation](https://onco.cc/terms/epigenetic-progenitor-theory/), [Hallmarks of Cancer](https://onco.cc/terms/hallmarks-of-cancer/), [Hallmarks of cancer as a synthesis of the theories](https://onco.cc/terms/hallmarks-synthesis/)
- key papers: [Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells](https://onco.cc/key-papers/paper-hallmarks-new-dimensions-cancer-discov-2022/)
- roadmaps: [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/)

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