ArticleClinical and translational medicine2022
Functional genomic analysis of epithelioid sarcoma reveals distinct proximal and distal subtype biology.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Epithelioid Sarcoma: A Review and Update.Cancers · 2026Review
- Multi-omics profiling identified two epithelioid sarcoma molecular subtypes with distinct signaling and immune characteristics.Cancer communications (London, England) · 2025Article
- Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers.Nature medicine · 2024Observational
- Translational Aspects of Epithelioid Sarcoma: Current Consensus.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Subclassification of epithelioid sarcoma with potential therapeutic impact.The Journal of pathology · 2023Article
- Functional genomic analysis of epithelioid sarcoma reveals distinct proximal and distal subtype biology.Clinical and translational medicine · 2022Article
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Authors and funding
22 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetastatic epithelioid sarcoma (EPS) remains a largely unmet clinical need in children, adolescents and young adults despite the advent of EZH2 inhibitor tazemetostat.
methodsIn order to realise consistently effective drug therapies, a functional genomics approach was used to identify key signalling pathway vulnerabilities in a spectrum of EPS patient samples. EPS biopsies/surgical resections and cell lines were studied by next-generation DNA exome and RNA deep sequencing, then EPS cell cultures were tested against a panel of chemical probes to discover signalling pathway targets with the most significant contributions to EPS tumour cell maintenance.
resultsOther biologically inspired functional interrogations of EPS cultures using gene knockdown or chemical probes demonstrated only limited to modest efficacy in vitro. However, our molecular studies uncovered distinguishing features (including retained dysfunctional SMARCB1 expression and elevated GLI3, FYN and CXCL12 expression) of distal, paediatric/young adult-associated EPS versus proximal, adult-associated EPS.
conclusionsOverall results highlight the complexity of the disease and a limited chemical space for therapeutic advancement. However, subtle differences between the two EPS subtypes highlight the biological disparities between younger and older EPS patients and emphasise the need to approach the two subtypes as molecularly and clinically distinct diseases.
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