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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 The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers.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.
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 The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers.
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 The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers.
Catalytic subunit of PRC2, writes H3K27me3.
3 products aim at EZH2: small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Tumour-associated overexpression: HPA finds the RNA tissue enhanced in normal bone marrow, lymphoid tissue, testis, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA EZH2: RNA tissue enhanced (bone marrow 24 nTPM, lymphoid tissue 34 nTPM, testis 25 nTPM); high antibody staining in 5 normal tissues; highest cancer staining skin cancer (12 of 12 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Sarcomas (soft tissue, bone, GIST), Prostate cancer); Open Targets associates it with 2 specific cancer types at or above 0.5 (diffuse large B-cell lymphoma, follicular lymphoma). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas EZH2 tissue; Human Protein Atlas EZH2 pathology; Open Targets ENSG00000106462 associations
First described 1996. Earliest sequence paper UniProt cites for the protein: Chen et al, Genomics, 1996, "Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Catalytic subunit of PRC2, writes H3K27me3.
RNA: tissue enhanced (bone marrow 24 nTPM, lymphoid tissue 34 nTPM, testis 25 nTPM), detected in many normal tissues.
Medium: Appendix, Bronchus, Cervix, Colon, Duodenum, Endometrium, Esophagus, Fallopian tube.
Medium only: thyroid cancer.
HPA EZH2 tissue · HPA EZH2 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| 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.
XNW5004 is an experimental small-molecule drug from Evopoint Biosciences in phase 2 trials for follicular lymphoma and prostate cancer, aimed at EZH2.
It gives the PD-L1-negative mesenchymal subtype, the group immunotherapy leaves behind, a mechanistic route back to immune visibility, and explains why immune infiltration and subtype are coupled.
The piece that turns a research classification into something a trial can use on one person's biopsy, with a probability attached rather than a flat label. It is the reason genetics-directed lymphoma trials became possible at all.
The genetic nosology that precision-medicine trials in diffuse large B-cell lymphoma now use to pick patients. It gives a mechanism, not just a label: two of the four subtypes point at a drug class that already exists.
It turned neuroendocrine transformation from a pathological curiosity into a mechanism with a genotype and a candidate intervention, and it is the reason EZH2 inhibitors are in prostate cancer trials at all.
Query for this target: (TITLE:"EZH2" OR ABSTRACT:"EZH2" OR TITLE:"PRC2" OR ABSTRACT:"PRC2") 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.
Shares Hallmark (2022): unlocking phenotypic plasticity, Cancer stem cell theory and phenotypic plasticity, Cancer stem cells & phenotypic plasticity, Epigenetic progenitor theory: cancer without a first mutation and the tag epigenetic.
Shares Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome and the tag epigenetic.
Shares Group trials by broken mechanism, not by organ or single mutation, Epigenetic progenitor theory: cancer without a first mutation, Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome, Epigenetic reprogramming and the tag epigenetic.
Shares Cell of origin in practice: Hans against expression profiling, and what it changes, The germinal centre reaction, LymphGen and the genetic clusters of large B-cell lymphoma, The germinal centre: why lymphoma starts where antibodies are made.
Shares Cell of origin in practice: Hans against expression profiling, and what it changes, Assign first-line treatment in diffuse large B-cell lymphoma by genetic subtype, not by a three-antibody stain, LymphGen and the genetic clusters of large B-cell lymphoma, A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications.
Shares The germinal centre reaction, The germinal centre: why lymphoma starts where antibodies are made, FLIPI, FLIPI2 and POD24 (follicular lymphoma risk), Cell of origin (GCB vs ABC).
Shares Cell of origin in practice: Hans against expression profiling, and what it changes, Assign first-line treatment in diffuse large B-cell lymphoma by genetic subtype, not by a three-antibody stain, LymphGen and the genetic clusters of large B-cell lymphoma, A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications.
Shares EZH2 gain-of-function mutation (Tyr646, originally Tyr641), Cell of origin in practice: Hans against expression profiling, and what it changes, MicroRNAs in cancer, Assign first-line treatment in diffuse large B-cell lymphoma by genetic subtype, not by a three-antibody stain.