Establishment and Characterization of a Panel of Patient-Derived Soft Tissue Sarcoma (Sts) Xenograft Models for in Vivo Testing of Novel Therapeutic Approaches

Abstract

ABSTRACT Aim: STS constitutes a rare, heterogeneous family of tumours of mesenchymal origin. The limited treatment options available for advanced STS underline the need for reliable preclinical models to test novel therapeutic strategies. Methods: Patient-derived xenografts were established in nu/nu NMRI mice by subcutaneous implantation of fresh, surgically resected tumour specimens from consenting patients with STS treated at University Hospitals Leuven. We mainly focused on STS subtypes which harbour specific genetic alterations (e.g. translocations, gene amplifications). Once tumour growth was observed, pieces of tumour were re-transplanted to a next generation of mice. At each passage tumour fragments were collected for histological and molecular characterization. Specific genomic alterations were confirmed in subsequent passages by fluorescence in situ hybridization. A STS xenograft model was considered to be established after observing stable histological and molecular features for at least two passages. Results: Until now we have transplanted a total of 65 patient-derived STS samples. We were able to successfully establish 12 well-characterized STS models maintaining the features of the original tumour: myxofibrosarcoma (3 models); dedifferentiated liposarcoma (2); synovial sarcoma (2); epithelioid haemangioendothelioma (1); malignant peripheral nerve sheath tumour (1); mesenchymal chondrosarcoma (1); leiomyosarcoma (1) and sarcoma not otherwise specified (1). Some of these models have already been successfully used for in vivo testing of novel agents including tyrosine kinase inhibitors or cytotoxic prodrugs. In addition, 12 other xenografts are still in early stages of engraftment, not yet fulfilling our criteria of “established model”. Conclusions: Our newly established STS xenografts maintain the histological and molecular characteristics of the original patient sample, therefore offering a promising preclinical platform for testing anti-cancer drugs. The availability of models of some ultra-rare entities would also allow us to study the biology of these diseases. Disclosure: All authors have declared no conflicts of interest.