Abstract 1031: XenoSarc: Patient-derived xenograft (PDX) models of soft tissue sarcoma (STS)—an update on a preclinical platform for early drug testing
Authors: Wozniak Agnieszka , Cornillie Jasmien , Gebreyohannes Yemarshet K. , Wang Yannick , Wellens Jasmien , Vanleeuw Ulla , Hompes Daphne , Stas Marguerite , Sinnaeve Friedl , Wafa Hazem , Debiec-Rychter Maria , Sciot Raf , Schöffski Patrick 
Published: August 2018

Background: STS constitutes a rare family of mesenchymal tumors with more than 70 subtypes described. The limited treatment options available for advanced STS underline the need for reliable preclinical models to test novel therapeutic strategies.

Methods: Panel of PDX models was established by subcutaneous implantation of fresh tumor specimens in immunodeficient, athymic nude NMRI mice. Once tumor growth was observed, pieces of tumor were re-transplanted to next generations of animals. At each passage tumor fragments were collected for detailed characterization. A model was considered established after observing stable histological and molecular features for at least two passages.

Results: Between 09/2011 and 11/2017, 228 STS samples from 203 consenting patients treated at University Hospitals Leuven, Belgium, have been transplanted. Thirty-three stable PDX models have been established, maintaining the histopathological and molecular features of the original tumor. Detailed clinical information about a donor patient, including sensitivity to given therapy, is linked to every model. Higher engraftment rate was observed in samples collected from patients who developed metastasis throughout the course of disease (38% vs. 23%, p&lt;0.05). Moreover, patients whose tumor successfully engrafted had significantly poorer overall survival (OS) than those whose tumor did not grow in mice (median OS 83 vs. 259 months; p&lt;0.05). XenoSarc platform includes models of gastrointestinal stromal tumor (6 models), myxofibrosarcoma (6), leiomyosarcoma (5), dedifferentiated liposarcoma (4), malignant peripheral nerve sheath tumor (2), synovial sarcoma (1), pulmonary artery intimal sarcoma (1), CIC-DUX4 fusion-positive round cell sarcoma (1), epithelioid haemangioendothelioma (1), mesenchymal chondrosarcoma (1), pleomorphic rhabdomyosarcoma (1), telangiectatic extraskeletal osteosarcoma (1), and high-grade undifferentiated pleomorphic sarcoma (3). These models are well-characterized, with detailed data on copy number changes and expression profile. In addition we have constructed tissue microarray (TMA), which can be used for target identification. 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, 17 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, Yannick Wang, Jasmien Wellens, Ulla Vanleeuw, Daphne Hompes, Marguerite Stas, Friedl Sinnaeve, Hazem Wafa, 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 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1031.