SWI/SNF chromatin remodeling complex and PRC2 histone methyltransferase play an important role in regulating gene expression in normal cells. EZH2 is the catalytic subunit of PRC2. In the previous study, EZH2 upregulation is associated with dysfunction of the SWI/SNF in cancer cells. SMARCB1 gene encodes INI1 protein, which is one of the important subunits of SWI/SNF. In 50 to 80% epithelioid sarcoma, loss of INI1 protein expression or biallelic SMARCB1 gene mutation had been found. Tazemetostat, an EZH2 inhibitor, has been shown the anti-tumor activity in advanced solid tumors. In a phase II study, 62 patients with INI1/SMARCB1-negative epithelioid sarcoma were received tazemetostat treatment. The ORR was 15% (9/62). The PFS was 5.5 months. The OS was 19.0 months. 26% of patients had disease control for more than 32 weeks. Based on these results, the FDA approved the treatment of tazemetostat for advanced epithelioid sarcoma.
Lancet Oncol. 2020 Nov;21(11):1423-1432