EZH2
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 The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers.
Tazemetostat was approved in epithelioid sarcoma (2020) and EZH2-mutant follicular lymphoma, but Ipsen withdrew it from all markets and indications on 9 March 2026 after the SYMPHONY-1 trial showed excess secondary haematologic malignancies (FDA alert March 2026). EZH2 inhibition continues to be explored (mevrometostat in prostate cancer; SCLC re-sensitisation), now under a safety cloud.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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 The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers.
- 1 · What it is
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 The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers.
- 2 · What goes wrong in cancer
Catalytic subunit of PRC2, writes H3K27me3.
- 3 · How drugs use it
2 products aim at EZH2: small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Biology
Catalytic subunit of PRC2, writes H3K27me3.
- Epithelioid sarcoma (INI1 loss)
- Follicular lymphoma
- Castration-resistant prostate cancer
How common it is, by cancer
| 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90% | INI1 (SMARCB1) loss in epithelioid sarcoma (EZH2 dependency) | Tazemetostat withdrawn March 2026 | FDA |
| Diffuse large B-cell lymphoma | 20-25% | EZH2 Y641 mutation in follicular/GCB lymphoma | Tazemetostat withdrawn March 2026 | Wikipedia |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.
An epigenetic drug that may re-sensitise prostate cancer to hormone therapy, in three phase 3 trials with enzalutamide.
Tazemetostat was the first EZH2 inhibitor, approved for epithelioid sarcoma and follicular lymphoma in 2020 and withdrawn worldwide in 2026 after secondary blood cancers.
Latest papers
topQuery 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.
Pages like this
not linked directly; found by shared links- TargetMenin
Shares Hallmark (2022): unlocking phenotypic plasticity, Cancer stem cells & phenotypic plasticity, Epigenetic reprogramming, Transcriptional machinery & addiction and the tag epigenetic.
- TargetIDH1 / IDH2
Shares Group trials by broken mechanism, not by organ or single mutation, Epigenetic reprogramming, Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET) and the tag epigenetic.
- TermHallmark (2022): non-mutational epigenetic reprogramming
Shares SWI/SNF chromatin remodelling, Drug-tolerant persister cells, Epigenetic reprogramming, Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET).
- TermHistologic transformation
Shares Hallmark (2022): unlocking phenotypic plasticity, Cancer stem cells & phenotypic plasticity, Lineage plasticity & neuroendocrine transformation, Follicular lymphoma.
- TargetCD79b
Shares Cell of origin (GCB vs ABC), Follicular lymphoma, Diffuse large B-cell lymphoma.
- ProductEnzalutamide
Shares MEVPRO-1, Transcriptional machinery & addiction, Lineage plasticity & neuroendocrine transformation, Prostate cancer.
- Key paperHallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells
Shares Hallmark (2022): unlocking phenotypic plasticity, Cancer stem cells & phenotypic plasticity, Epigenetic reprogramming.
- ProductRevumenib
Shares Cancer stem cells & phenotypic plasticity, Epigenetic reprogramming, Transcriptional machinery & addiction, Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET).