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 The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers. This dossier gathers the 2 products (0 approved), 1 trial, 6 pathways and 1 resistance route in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
Catalytic subunit of PRC2, writes H3K27me3.
- Epithelioid sarcoma (INI1 loss)
- Follicular lymphoma
- Castration-resistant prostate cancer
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Sarcomas | >90% | INI1 (SMARCB1) loss in epithelioid sarcoma (EZH2 dependency) | Tazemetostat withdrawn March 2026 | FDA |
| Diffuse large B-cell lymphoma | 20-25% | EZH2 Y641 mutation in follicular/GCB lymphoma | Tazemetostat withdrawn March 2026 | Wikipedia |
| Prostate cancer | n/a | Overexpression in CRPC; no threshold | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Products by modality and phase
Browse products →| Modality | Phase 3 | Withdrawn or failed |
|---|---|---|
| Small molecule 2 |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| MEVPRO-1 NCT06551324 | 3 | Recruiting | mCRPC after abiraterone: mevrometostat + enzalutamide vs physician's choice (enzalutamide or docetaxel) |
Resistance routes that involve this target
Unaddressed routes →Schlafen-11 is required for replication-stress-induced death; its epigenetic silencing confers resistance to TOP1 (and platinum) agents.
- ATR/CHK1 inhibitors re-sensitise SLFN11-low cells preclinically
- EZH2 inhibition to restore SLFN11 (preclinical)
Pathways where it is a node
Pathway-to-drug matrix →- Cancer stem cells & phenotypic plasticityNode: EZH2, SWI/SNF, TP53/RB1 loss · 2 druggable nodes
Some cancer cells behave like stem cells: they can regrow the whole tumour, resist treatment, and switch identities. This plasticity explains why tumours come back and why some lung and prostate cancers transform into a different cancer type under therapy.
Which nodes have drugs → - Cold tumours: immune deserts and exclusionNode: CXCL9/10 silenced (EZH2) · 6 druggable nodes
Tumours come in three immune weathers: inflamed (T cells inside, checkpoint drugs work), excluded (T cells stuck at the edge), and desert (no T cells at all). Most common cancers are excluded or desert, and turning them 'hot' is the central problem of immunotherapy.
Which nodes have drugs → - Drug-tolerant persister cellsNode: KDM5A, H3K27me3, YAP, NF-κB · 3 druggable nodes
Even when a drug wipes out 99% of a tumour, a few cells survive without any resistance mutation: they go quiet, stop dividing, and wait. These persisters are the seed of relapse. They are hard to kill precisely because they are not doing much, but they have their own weaknesses.
Which nodes have drugs → - Epigenetic reprogrammingNode: Histone marks (EZH2, KMT2A, H3K27M) · 3 druggable nodes
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.
Which nodes have drugs → - Lineage plasticity & neuroendocrine transformationNode: SOX2, EZH2, ASCL1/NEUROD1 · 5 druggable nodes
Under pressure from a drug that blocks its identity (the androgen receptor in prostate cancer, EGFR in lung cancer), a tumour can change what kind of cell it is, becoming a small-cell neuroendocrine cancer that no longer needs the blocked signal. It is the ultimate escape: not a new mutation in the engine, but a new engine.
Which nodes have drugs → - SWI/SNF chromatin remodellingNodes: SMARCB1 loss → EZH2, PRC2 (EZH2) antagonism · 2 druggable nodes
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.
Which nodes have drugs →
Companion diagnostics and assays
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →Query for this target: (TITLE:"EZH2" OR ABSTRACT:"EZH2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about EZH2, not a curated reading list.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/ezh2.json. Licence CC BY 4.0.