Small animal models for the study of bone sarcoma pathogenesis: characteristics, therapeutic interests and limitations

Osteosarcoma, Ewing sarcoma and chondrosarcoma are the three main entities of bone sarcoma which collectively encompass more than 50 heterogeneous entities of rare malignancies. In contrast to osteosarcoma and Ewing sarcoma which mainly affect adolescents and young adults and exhibit a high propensity to metastasise to the lungs, chondrosarcoma is more frequently observed after 40 years of age and is characterised by a high frequency of local recurrence. The combination of chemotherapy, surgical resection and radiotherapy has contributed to an improved outcome for these patients. However, a large number of patients still suffer significant therapy related toxicities or die of refractory and metastatic disease. To better delineate the pathogenesis of bone sarcomas and to identify and test new therapeutic options, major efforts have been invested over the past decades in the development of relevant pre-clinical animal models. Nowadays, in vivo models aspire to mimic all the steps and the clinical features of the human disease as accurately as possible and should ideally be manipulable. Considering these features and given their small size, their conduciveness to experiments, their affordability as well as their human-like bone-microenvironment and immunity, murine pre-clinical models are interesting in the context of these pathologies. This chapter will provide an overview of the murine models of bone sarcomas, paying specific attention for the models induced by inoculation of tumour cells. The genetically-engineered mouse models of bone sarcoma will also be summarized.