Genetically engineered mouse models and human osteosarcoma

Osteosarcoma (OS) is the most common primary tumour of bone. It is most frequent in children and adolescents with an incidence of 7.3 per 1 million of the population [1]. Although OS is mainly classified as a childhood disease, a second peak of incidence is reported in the elderly population [1]. The majority of OS tumours are situated in the long bones with a small proportion located in the pelvis and axial skeleton [2,3]. OS has a relatively high metastatic rate, with the lung being the most common site of spread.The current treatment for OS revolves around the use of chemotherapy, radiotherapy and the surgical removal of the tumour. The chemotherapeutic regimen for OS patients combines cisplatin, doxorubicin and high doses of methotrexate [4]. Surgical resection is coupled with limb salvage procedures to remove malignant tissue and minimize the impact on quality of life.The lack of new therapeutic options for the management of OS has translated to a stagnation of patient outcomes [5,6]. Survival and prognosis rates have remained largely unchanged in two decades despite increased detection and monitoring afforded by advances in clinical imaging modalities [7-9]. Furthermore, there are difficulties associated with the study of OS in humans, such as recruiting sufficient patients to allow clinical insights in trialing new treatment options. A key component to improving patient outcome will be the development and application of faithful experimental models of human OS. Such models can serve as a preclinical platform for the identification of new therapeutic targets and the in vivo testing and triaging of those proposed for human trials. Experimentally derived interventions could then be developed in in vivo models where therapies can be rigorously evaluated side by side prior to human evaluation. Equally importantly, experimental OS models serve as a means to further understand the genetics and biology of OS with an emphasis on metastatic disease.Robust animal models