Epigenetic reprogramming
Cells can change behaviour without changing their DNA sequence, by rewriting the chemical tags that decide which genes are read. Cancers silence brakes and antigens this way, and switch identity under drug pressure. Unlike mutations, tags can be erased.
Diagram
Pick a product above a diagram to see the nodes it hits and the escape routes below the block. Hover or tap any node or arrow for what it is; every node opens its target, glossary entry or the pathway page. Violet boxes are druggable targets.
The genome is the book; epigenetics is the highlighting and the pages stapled shut. Cancer staples shut the safety chapters and highlights the growth chapters. Epigenetic drugs pull staples.
A librarian who unlocks shelves on request. When one librarian is fired the other covers both shifts; fire the second and the library stops working. That second librarian is the drug target.
What happens
In plain words, then the glossary entries the stage rests on. Chapter 2, How a cell becomes cancer: Cancer is evolution inside a body.
Cells can change behaviour without changing their DNA sequence, by rewriting the chemical tags that decide which genes are read. Cancers silence brakes and antigens this way, and switch identity under drug pressure. Unlike mutations, tags can be erased.
Epigenetic reprogramming. Cancer changes not just its genes but how they are read: chemical tags on DNA and histones silence guardians and awaken growth programmes. Unlike mutations, these changes are reversible, which is the hope behind epigenetic drugs.
SWI/SNF chromatin remodelling. A machine that opens and closes DNA so genes can be read. One in five cancers has a broken part (ARID1A, SMARCA4, PBRM1), and losing one part often creates a dependence on its twin, which is the basis for new synthetic-lethal drugs.
The molecular players
The proteins and genes at this stage, with their role and how many products act on each. Listed players come from the atlas; drawn players sit as nodes in the diagrams above.
A metabolic enzyme whose mutant form produces a molecule that scrambles how genes are read; blocking it slows brain tumours and leukaemias.
EZH2 is an enzyme that silences genes. The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers.
A gene fusion that drives an aggressive leukaemia in infants and adults. It cannot be blocked directly, but the scaffold protein it depends on (menin) can.
A scaffold protein that certain leukaemias need to keep their genes switched on; the first drug against it was approved in 2024.
Where medicines act
Products grouped by the node they hit, most advanced first, with the cancers an approved product is linked to. Pick one above the diagram to see it light up.
- VorasidenibApprovedGlioma & glioblastomaAstrocytoma, IDH-mutant (grades 2 to 4)Oligodendroglioma, IDH-mutant and 1p/19q-codeleted
- EnasidenibApprovedAcute myeloid leukaemiaIDH1- and IDH2-mutated acute myeloid leukaemiaSinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma
- IvosidenibApprovedAcute myeloid leukaemiaBiliary tract cancer (cholangiocarcinoma)IDH1- and IDH2-mutated acute myeloid leukaemia
- OlutasidenibApprovedAcute myeloid leukaemiaIDH1- and IDH2-mutated acute myeloid leukaemia
- Oncomine Dx Target TestApprovedNon-small-cell lung cancerBiliary tract cancer (cholangiocarcinoma)
- HMPL-306Phase 3
- SafusidenibPhase 3
- TQB3454Phase 3
- TazemetostatWithdrawn
- MevrometostatPhase 3
- XNW5004Phase 2
How tumours escape
Records tied to this stage that describe resistance, evasion or tolerance. The resistance atlas lists the routes class by class.
- early clinicalclinicRead the spinal fluid to track brain tumours without opening the skull
Fluid taken from the lower back contains DNA from brain tumours. Testing it can diagnose, monitor and detect resistance without brain surgery.
- preclinical evidenceresearchDesign drug pairs where resisting one makes you vulnerable to the other
Choose two treatments so that whatever the tumour does to escape the first, it becomes easier to kill with the second. The immune system is a good candidate partner.
- 2023translationalAUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutationNaturechanged practice
- 2022reviewHallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cellsCancer Discovery
Measured by
Biomarkers, tests and assays in the corpus that read this stage in a patient.
Open questions
What is not known at this stage: the atlas's own questions, the bottlenecks it bears on, and the ideas in the corpus that try to answer them.
- Why do epigenetic drugs work in blood cancers and rarely in solid tumours?
- Can epigenetic editing switch a single silenced gene back on in patients?
- early clinicalindustryAn open-science consortium on the undruggable drivers, open until a candidate
Companies and public funders would pool money and scientists to crack the hardest cancer proteins, such as MYC and mutant p53, sharing everything openly until there is a real drug candidate, then competing on the final product.
- early clinicalresearchGroup trials by broken mechanism, not by organ or single mutation
Rare cancers often share a broken cellular machine even when they arise in different organs. Grouping patients by that shared fault makes trials possible.
- early clinicalMenin inhibitors for infant KMT2A-rearranged ALL
Infant leukaemia is driven almost entirely by KMT2A fusions, which menin inhibitors were built to attack. Add them to the new blinatumomab-containing backbone.
- early clinicalresearchUnmask hidden antigens with a short epigenetic course before immunotherapy
Low doses of drugs that change how DNA is packaged can make cancer cells display more of what marks them as abnormal, potentially waking up immunotherapy in cold tumours.
- preclinical evidenceresearchBlock the chemical switch that lets cells hide from treatment
Cells that survive treatment do so by changing which genes they use, not their DNA. Drugs that block that change may stop survivors from forming at all.
- speculativeregulatorDevelop drugs in children first when the target is a children's target
Children wait years for drugs because adult trials come first, even when the target belongs to a childhood cancer. Some drugs should start with children.
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2023translationalAUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutationNaturechanged practice
- 2023rctINDIGO: vorasidenib, the first targeted drug for IDH-mutant low-grade gliomaNew England Journal of Medicinechanged practice
- 2022reviewHallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cellsCancer Discovery
- 2020reviewMammalian SWI/SNF Chromatin Remodeling Complexes: Emerging Mechanisms and Therapeutic StrategiesTrends in genetics
- 2017translationalRecurrent IDH2 R172X mutations in sinonasal undifferentiated carcinomaModern Pathologychanged practice
- 2016reviewEpigenetic Determinants of CancerCold Spring Harbor perspectives in biology
src/data/mechanics-atlas.ts). Players, medicines, escape routes, tests, ideas and papers are resolved from the knowledge graph at build time through the stage's pathways, targets and terms, so every item here has its own page and sources. Where a section is missing, the corpus has no record tied to the stage yet. Nothing here is medical advice; see about and methodology. Stage 2.4 of 56.