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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Epithelioid sarcoma is a rare soft tissue cancer that has lost a gene brake called SMARCB1, leaving it dependent on the enzyme EZH2. Surgery cures localised tumours. The EZH2 inhibitor tazemetostat was approved in 2020 and withdrawn worldwide in March 2026 after secondary blood cancers in a lymphoma trial; the dependency it proved is still a target in development, and chemotherapy remains in use.
Epithelioid sarcoma is defined by loss of SMARCB1 (INI1), a core subunit of the SWI/SNF chromatin-remodelling complex, in over 90 percent of cases. SWI/SNF loss makes cells dependent on the antagonistic polycomb repressive complex 2 and its catalytic subunit EZH2, a synthetic-lethal relationship demonstrated in preclinical models and confirmed in patients. The distal (classic) type presents as slow-growing nodules on the hands and forearms of young adults and is often misdiagnosed as a benign lesion; the proximal type, in the pelvis, perineum and trunk, is larger and more aggressive, with rhabdoid features. Both spread to lymph nodes, which is unusual for sarcomas, and to lung.
Localised disease is treated with wide resection and radiotherapy according to soft tissue sarcoma principles; sentinel node evaluation is considered because of nodal spread. Conventional chemotherapy (anthracycline, ifosfamide, gemcitabine-docetaxel) has modest activity. Tazemetostat received FDA accelerated approval in January 2020 for metastatic or locally advanced epithelioid sarcoma not eligible for complete resection, on the basis of the single-arm EZH-202 cohort (objective responses in a minority, but durable, with a benign safety profile). The confirmatory randomised trial EZH-301 adds tazemetostat to doxorubicin in the first line; it was meant to decide whether the accelerated approval would be converted, but Ipsen withdrew the drug in all indications on 9 March 2026 after the SYMPHONY-1 follicular lymphoma trial's data monitoring committee flagged secondary haematologic malignancies (18 of 318 patients, 5.7%, per the FDA safety communication).
| Setting | Approach | Guideline |
|---|---|---|
| Localised | Wide resection with negative margins plus radiotherapy for large, deep or close-margin tumours; lymph node assessment considered because of nodal spread. | NCCN Category 2A |
| Advanced or metastatic | Anthracycline-based chemotherapy; tazemetostat (accelerated approval 2020, EZH-202) was withdrawn from all markets in March 2026 after SYMPHONY-1 showed excess secondary blood cancers, so the EZH2 option is gone; clinical trial enrolment encouraged. | NCCN Category 2A |