Abstract A004: Establishing the First Integrated Research Infrastructure and Preclinical Models for EWSR1 Fusion-Positive Myoepithelial Carcinoma

Abstract Myoepithelial carcinoma (MEC) is an ultra-rare malignancy, with an incidence of 0.013/100,000, characterized by aggressive clinical behavior and the absence of established therapies. MEC can affect adult and pediatric populations, with adult disease more commonly seen in the salivary gland and pediatric disease more commonly seen in soft tissues. In pediatric cases, recurrent gene fusions—most frequently involving EWSR1 with partners such as KLF15—define MEC as a fusion-driven cancer. Despite this, progress has been impeded by limited biospecimen availability, lack of coordinated research infrastructure, and absence of validated preclinical models. To address these barriers, cureMEC: The Myoepithelial Carcinoma Project was established in 2022 as a patient-driven nonprofit dedicated to advancing translational research in MEC. In collaboration with the Rare Cancer Research Foundation (RCRF) and Pattern.org, cureMEC has developed the first dedicated MEC biorepository and integrated data platform, enabling specimen collection, molecular profiling, and open research access. Through strategic partnerships, MEC samples are now included in large-scale fusion-cancer initiatives encompassing transcriptomics, proteomics, and drug-screening pipelines. Early efforts have yielded the first coordinated biobanking network for MEC, capturing clinically annotated specimens across multiple institutions, including at least 75 cases so far. Two novel MEC cell lines and a patient-derived xenograft (PDX) model have been generated and molecularly validated for EWSR1-KLF15 and related fusions. These models will be used to validate EWSR1-KLF15 as a recurrent fusion in MEC and will be probed for differential surface-protein expression patterns that may represent potential therapeutic targets. Parallel high-throughput drug-repurposing studies are being launched to assess sensitivity patterns across fusion-defined models. cureMEC is establishing the first integrated research ecosystem for MEC, centered on fusion biology and patient partnership. By coupling coordinated biospecimen infrastructure with proteogenomic discovery, this initiative is creating essential tools to elucidate MEC pathogenesis and accelerate the development of targeted therapies. This model demonstrates how patient-driven collaborations can rapidly advance research for fusion-positive rare cancers and catalyze progress toward clinical translation. Citation Format: Jamie D. Barber, Barbara Van Hare, Naomi Natale, Michael Casaus. Establishing the First Integrated Research Infrastructure and Preclinical Models for EWSR1 Fusion-Positive Myoepithelial Carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Fusion-Positive Cancer: From Discovery to Therapy; 2026 Jan 13-15; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(1_Suppl):Abstract nr A004.