Abstract
Abstract Background: STS constitutes a rare and very heterogeneous family of mesenchymal tumors. The limited treatment options available for advanced STS underline the need for reliable preclinical models to test novel therapeutic strategies. Methods: A panel of patient-derived xenografts (PDX) was established by subcutaneous implantation of fresh, surgically resected or biopsied tumor specimens in immunodeficient, athymic nude NMRI mice. Once tumor growth was observed, pieces of tumor were re-transplanted to next generations of mice. At each passage tumor fragments were collected for histopathological and molecular characterization. A model was considered established after observing stable histological and molecular features for at least two passages. Results: Until now 171 STS samples from consenting patients treated at the University Hospitals, Leuven, Belgium, have been transplanted. Twenty-eight well-characterized, stable PDX models of STS have been established, maintaining the histopathological and molecular features of the original tumor. The detailed clinical information about a donor patient, including sensitivity to standard and experimental drugs, is linked to every model. At this point the XenoSarc platform includes models of gastrointestinal stromal tumor (6 models), myxofibrosarcoma (6), dedifferentiated liposarcoma (3), malignant peripheral nerve sheath tumor (3), synovial sarcoma (1), leiomyosarcoma (4), epithelioid haemangioendothelioma (1), mesenchymal chondrosarcoma (1), pleomorphic rhabdomyosarcoma (1) and high-grade undifferentiated pleomorphic sarcoma (2). From these models we have also available tissue microarray (TMA) as well as data on genomic and/or expression profile including mutations (by RNA-Seq). Some of these models have already been successfully used for in vivo testing of novel agents, including both targeted and cytotoxic (pro-)drugs, and results served as a rationale for several prospective clinical trials. In addition, 24 other xenografts are still in early stages of engraftment, not yet fulfilling our criteria of an “established model”. Conclusion: Our XenoSarc platform contains a number of well-annotated models, characterized by stable histological and molecular features. This platform is a reliable tool for the evaluation of new anticancer treatments for STS and for studying the biology of these rare diseases. The platform is made available to collaborators from academia and industry. Citation Format: Agnieszka Wozniak, Jasmien Cornillie, Yemarshet K. Gebreyohannes, Jasmien Wellens, Lise Vreys, Daphne Hompes, Marguerite Stas, Friedl Sinnaeve, Maria Debiec-Rychter, Raf Sciot, Patrick Schöffski. XenoSarc: Patient-derived xenograft (PDX) models of soft tissue sarcoma (STS), an update on a preclinical platform for early drug testing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4811. doi:10.1158/1538-7445.AM2017-4811
Published Version
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