The potential of emerging therapeutics for epithelioid sarcoma

ABSTRACT

Introduction: Epithelioid sarcoma (ES) is a rare malignancy of mesenchymal origin that accounts for <1% of soft tissue sarcomas. Research in ES has been limited by its rarity, and there are no standardized treatment recommendations.

Areas covered: A PubMed search for the key terms including epithelioid sarcoma, chemotherapy, systemic therapy and abstracts were reviewed for reports on chemotherapy treatment and outcomes in ES. There were no prospective trials limited to ES. Available data included case reports, single-institution retrospective series, and multi-institutional retrospective analyses. Small, retrospective series have identified a role for palliative chemotherapy, though overall outcomes remain poor for patients with metastatic disease. Over 90% of tumors are known to exhibit loss of Integrase Interactor 1 (INI1), and there is emerging interest in utilizing this as a potential therapeutic target. Additional signaling pathways including mammalian target of rapamycin (mTOR) and epidermal growth factor (EGF) have been implicated in the pathogenesis of ES.

Expert opinion: Given the limited efficacy of traditional cytotoxic agents, the development of novel treatment strategies is an area of unmet need. As the understanding of the pathogenic mechanisms in epithelioid sarcoma improves, targeting of critical pathways may produce promising treatments in the future.

KEYWORDS:

• Epithelioid sarcoma
• INI1
• SMARCB1
• drug therapy

Article highlights

• ES is a rare soft tissue sarcoma with high risk of loco-regional recurrence and metastatic disease despite adequate surgical resection.

• There is limited data from small retrospective investigations on the benefit of systemic chemotherapy in the metastatic setting.

• Based on available data, one chemotherapy regimen is not clearly superior. Therefore, there is no best standard chemotherapy treatment for ES.

• Loss of INI1 is found in the vast majority of ES and is known to play a key role in its pathogenesis, making this a potential therapeutic target.

• Further research into the biology of ES is needed to allow the development of targeted therapies with the goal of developing a standard of care and ultimately improving patient outcomes.

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Declaration of interest

R Chugh is Medical Advisory Board member for Epizyme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper is not funded.