尤文肉瘤是一种侵袭性儿科癌症，由 EWS::FLI1 融合蛋白驱动，该融合蛋白通过劫持 BAF 染色质重塑复合物来破坏基因表达。该机制的核心是生物分子缩合物的形成，由 EWS 的朊病毒样结构域 (PrLD) 和核心 BAF 亚基 ARID1A 介导。 ARID1A 是 EWS::FLI1 和 BAF 复合物之间的关键接口，其冷凝物形成能力对于驱动肿瘤生长的异常基因表达至关重要。冷凝物活性 ARID1A 的丧失会显着损害肿瘤进展，使其成为潜在的治疗靶点。然而，由于所涉及的相互作用的瞬态性，靶向冷凝物的形成具有挑战性，这使得有效抑制剂的开发变得复杂。这项工作强调了进一步研究旨在破坏尤文肉瘤和其他相关恶性肿瘤中凝结物形成的治疗策略的重要性。© 2024 作者。约翰·威利出版的《分子肿瘤学》

Ewing sarcoma, an aggressive pediatric cancer, is driven by the EWS::FLI1 fusion protein, which disrupts gene expression by hijacking the BAF chromatin remodeling complex. Central to this mechanism is the formation of biomolecular condensates, mediated by the prion-like domains (PrLDs) of EWS and ARID1A, a core BAF subunit. ARID1A serves as a critical interface between EWS::FLI1 and the BAF complex, with its condensate-forming ability essential for the aberrant gene expression that drives tumor growth. The loss of condensate-competent ARID1A significantly impairs tumor progression, identifying it as a potential therapeutic target. However, targeting condensate formation is challenging due to the transient nature of the interactions involved, complicating the development of effective inhibitors. This work underscores the importance of further investigation into therapeutic strategies aimed at disrupting condensate formation in Ewing sarcoma and other related malignancies.© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.