Purpose of review Epithelioid sarcoma (ES) is one of the ultra-rare subtypes of soft tissue sarcomas, with an incidence <0.5 new cases/million/year. It is characterized by loss of SMARCB1 expression, a member of chromatin remodelling complexes, leading to transcriptional dysregulation and dependence on the PRC2 complex, with its histone methyltransferase EZH2. This review summarizes the current therapeutic landscape of ES and explores advances in its molecular characterization as well as potential new treatment options. Recent findings Loss of SMARCB1 in ES is mostly related to homozygous deletion of its locus in chromosome 22. Lack of SMARCB1 leads to global transcriptional changes and the identification of two distinct molecular subtypes that closely resemble the classical and proximal histological subtypes of ES. Transcriptional analyses revealed new potential therapeutic targets, including MYC, mTOR, and TEK. Dependence on EZH2 led to the approval of the EZH2 inhibitor tazemetostat for the treatment of advanced ES; however, multiple resistance mechanisms that decreased its activity have been characterized, and its use recently discontinued due to unexpected secondary hematological malignancies. Summary Despite progress in understanding ES biology, treatment options are limited, and prognosis remains poor. Further studies are needed, but the rarity of the disease limits opportunities for conducting dedicated clinical trials or broader molecular characterization.
Sobczuk et al. (Tue,) studied this question.