PO.SHP01.02 · 科学与健康政策
构建首个针对肌上皮癌的综合研究生态系统和临床前模型平台
Building the first comprehensive research ecosystem and preclinical model platform for myoepithelial carcinoma
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
肌上皮癌（MEC）是一种极为罕见、临床侵袭性强的恶性肿瘤（发病率 0.013/100,000），可影响儿童和成人，发生于多种解剖部位，最常见于唾液腺和软组织。尽管其病情严重，MEC 仍严重研究不足，缺乏既定的治疗标准，且历来对生物标本、分子数据或疾病相关模型的获取有限。虽然反复出现的基因融合（最常涉及 EWSR1 与 ATF1、KLF15、KLF17、PBX1 和 POU5F1 等伙伴基因）定义了一部分儿童和青壮年病例，但 MEC 总体上表现出尚未被系统性表征的显著生物学异质性。为应对长期存在的进展障碍，cureMEC：肌上皮癌项目于 2022 年启动，作为一项由患者驱动的研究倡议，致力于构建跨分子亚型研究 MEC 所需的基础设施。cureMEC 与罕见癌症研究基金会（RCRF）和 Pattern.org 合作，建立了首个专门的 MEC 生物样本库和整合的临床-分子数据平台，支持系统性标本采集、多组学分析和开放获取的研究参与。MEC 生物标本现已被纳入涵盖转录组学、蛋白质组学和高通量药物筛选流程的大规模项目。早期成果包括创建了首个协调一致的 MEC 生物样本库网络，建立了两个新的 MEC 细胞系，并鉴定了一个经分子确认携带 EWSR1-KLF15 的患者来源异种移植（PDX）。这些模型将支持 EWSR1 驱动的肿瘤发生的机制研究、用于识别治疗靶点的表面蛋白图谱绘制，以及跨融合定义情境的高通量药物再利用筛选。这些努力共同建立了首个针对 MEC 的整合研究生态系统，将患者伙伴关系、生物标本基础设施和蛋白基因组学发现结合起来。该模式展示了患者驱动的合作如何能够为极罕见癌症迅速构建基础性科学资源，创造出阐明疾病机制并加速靶向疗法开发所需的工具。
查看英文原文 English abstract
Myoepithelial carcinoma (MEC) is an ultra-rare, clinically aggressive malignancy (incidence 0.013/100,000) that affects both children and adults and arises in diverse anatomic sites, most commonly the salivary gland and soft tissues. Despite its severity, MEC remains profoundly understudied, with no established therapeutic standards and historically limited access to biospecimens, molecular data, or disease-relevant models. Although recurrent gene fusions, most frequently involving EWSR1 with partners such as ATF1, KLF15, KLF17, PBX1, and POU5F1, define a subset of pediatric and young adult cases, MEC overall exhibits substantial biological heterogeneity that has yet to be systematically characterized. To address longstanding barriers to progress, cureMEC: The Myoepithelial Carcinoma Project was launched in 2022 as a patient-driven research initiative dedicated to building the foundational infrastructure required to study MEC across molecular subtypes. In partnership with the Rare Cancer Research Foundation (RCRF) and Pattern.org, cureMEC has established the first dedicated MEC biorepository and integrated clinical-molecular data platform, supporting systematic specimen acquisition, multiomic profiling, and open-access research engagement. MEC biospecimens are now incorporated into large-scale programs spanning transcriptomics, proteomics, and high-throughput drug-screening pipelines. Early achievements include creation of the first coordinated MEC biobanking network and establishment of two novel MEC cell lines have been developed and identification of a patient-derived xenograft (PDX) molecularly confirmed to harbor EWSR1-KLF15. These models will support mechanistic studies of EWSR1-driven oncogenesis, surface-protein mapping to identify therapeutic targets, and high-throughput drug-repurposing screens across fusion-defined contexts. Together, these efforts establish the first integrated research ecosystem for MEC, combining patient partnership, biospecimen infrastructure, and proteogenomic discovery. This model demonstrates how patient-driven collaborations can rapidly build foundational scientific resources for ultra-rare cancers, creating the tools necessary to elucidate disease mechanisms and accelerate the development of targeted therapies.
利益披露 Disclosure
J. Barber, None..
N. Natale, None..
M. Casaus, None.