Generation and characterization of patient-derived xenografts from patients with osteosarcoma

Abstract

BackgroundStandard therapy of osteosarcoma (OS) rests on cytotoxic regimes, which dramatically limits the further improvement in the prognosis of patients with OS. Preclinical models of OS are extremely urgent to break this impasse. Materials and MethodsHere, we describe our experience of developing patient-derived tumor xenografts (PDXs) using surgical samples from patients with OS. All the xenografts growing subcutaneously in mice will be identified pathologically and genetically. Furthermore, we explored the consistency of the drug sensitivity between the PDX models and corresponding patients against specific regimens. ResultsWe generated nine OS PDXs from 21 surgical resections of primary OS tumors, with an engraftment rate of 42.9 %. Morphological and immunohistochemical (SATB2, MDM2, CDK4, and Ki67) studies and whole-exome sequencing showed a remarkable similarity between the patient’s tumor and corresponding PDX, which was maintained over several passages in mice. A therapeutic combination of Pirarubicin and Cisplatin was tested against two OS PDX models, in which the corresponding patient was insensitive and sensitive to the regimen, respectively. ConclusionThe panel of OS PDX models faithfully mirrored morphologic and genetic features of OS, representing reliable models to test therapeutic approaches.