XenoSarc:用于早期药物测试的患者来源的软组织肉瘤(STS)异种移植(PDX)模型的综合平台。

P. Schöffski, Britt Van Renterghem, J. Cornillie, Yanni Wang, Y. Gebreyohannes, Che-Jui Lee, J. Wellens, U. Vanleeuw, Madita Nysen, D. Hompes, M. Stas, F. Sinnaeve, H. Wafa, B. Topal, T. Verbelen, M. Debiec-Rychter, R. Sciot, A. Wozniak
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引用次数: 1

摘要

37背景:STS是一个罕见的异质性肿瘤家族,有70多种亚型。鉴于治疗选择有限,迫切需要可靠的临床前模型,尤其是STS的孤儿亚型。方法:通过皮下植入无胸腺NMRI小鼠的新鲜肿瘤标本建立PDX模型。生长中的肿瘤块被重新移植到下一代小鼠身上。在每个传代时收集片段用于组织学/分子表征。在观察到至少2个传代的稳定特征后,认为模型已经“建立”。储存离体小鼠组织样本,通过免疫组织化学/流式细胞术进行表征,并用于体外药物测试。结果:2011-2019年间,来自301名自愿患者的329份样本被移植;建立了56个模型,另外16个模型处于早期通过阶段。关于供体和肿瘤的临床信息(包括对标准和实验药物的敏感性)是可用的。该平台包括去分化脂肪模型(10个模型)、粘纤维模型(8个)、平滑肌模型(7个)、滑膜模型(2个)、内膜模型(2)、CIC阳性圆细胞模型(1个)、间充质软骨模型(1)、骨外骨模型(1种)、粘液样脂肪模型(1份)、粘炎性成纤维细胞模型(一份)、横纹肌模型(2份)和高级未分化多形性肉瘤模型(7份),以及GIST模型(8份),MPNST(4)和上皮样血管内皮瘤(1)。模型具有良好的特征,可以获得关于拷贝数变化(低覆盖率全基因组测序)和基因表达谱(RNA-Seq)的分子信息。我们还从异种移植物中构建了组织微阵列,用于临床前研究的靶点识别和模型选择。异种移植物可用于新型药物的体内测试,其结果已成为许多前瞻性临床试验的基本原理。结论:XenoArc为研究包括超罕见实体在内的多种肉瘤亚型的生物学提供了机会,是临床STS试验准备中早期药物筛选的宝贵工具。该平台维护良好,并不断扩展,可供学术界和工业界的合作者使用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
XenoSarc: A comprehensive platform of patient-derived xenograft (PDX) models of soft tissue sarcoma (STS) for early drug testing.
37 Background: STS is a family of rare, heterogeneous tumors with > 70 subtypes. There is an urgent need for reliable preclinical models, especially for orphan subtypes of STS, given the limited treatment options. Methods: A panel of PDX models was established by s.c. implantation of fresh tumor specimens in athymic NMRI mice. Growing pieces of tumor were re-transplanted to next generations of mice. At each passage fragments were collected for histological/molecular characterization. A model was considered “established” after observing stable features for at least 2 passages. Ex-mouse tissue samples were stored, characterized by immunohistochemistry/flow cytometry and used for in vitro drug testing. Results: Between 2011-2019, 329 samples from 301 consenting patients were transplanted; 56 models are established, 16 additional models are in early passaging. Clinical information about donor and tumor (including sensitivity to standard and experimental agents) is available. The platform includes models of dedifferentiated lipo- (10 models), myxofibro- (8), leiomyo- (7), synovial (2), intimal (2), CIC-positive round cell (1), mesenchymal chondro- (1), extraskeletal osteo- (1), myxoid lipo- (1), myxoinflammatory fibroblastic (1), rhabdomyo- (2) and high-grade undifferentiated pleomorphic sarcoma (7), as well as GIST (8), MPNST (4) and epithelioid hemangioendothelioma (1). Models are well-characterized, with molecular information on copy number changes (low-coverage whole genome sequencing) and gene expression profile (RNA-Seq) available. We also constructed tissue microarrays from the xenografts which are used for target identification and model selection for preclinical studies. Xenografts are available for in vivo testing of novel agents, and results already served as a rationale for a number of prospective clinical trials. Conclusions: XenoSarc offers opportunities for studying the biology of a variety of sarcoma subtypes including ultra-rare entities and is a valuable tool for early drug screening in preparation of clinical STS trials. The platform is well maintained and continuously expanded, and available to collaborators from academia and industry.
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审稿时长
20 weeks
期刊介绍: The Journal of Global Oncology (JGO) is an online only, open access journal focused on cancer care, research and care delivery issues unique to countries and settings with limited healthcare resources. JGO aims to provide a home for high-quality literature that fulfills a growing need for content describing the array of challenges health care professionals in resource-constrained settings face. Article types include original reports, review articles, commentaries, correspondence/replies, special articles and editorials.
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