Corrigendum: Animal models in osteosarcoma

Preclinical In Vivo Modeling of Pediatric Sarcoma—Promises and Limitations

“…Inactivation of Tp53 alone or together with Rb in Prx-1 positive cells (mesenchymal/skeletal progenitors) Osx , Col1A1 , or Og2 positive cells (pre-osteoclasts and osteoclasts) generates OS with high penetrance often leading to metastatic disease [ 100 , 101 , 102 , 103 , 104 , 105 , 106 ]. For a detailed summary of genetically engineered mouse models for OS, see Figure S1 , and recent reviews provided by Guijarro et al [ 107 ] and Uluçkan et al [ 108 ].…”

“…Most importantly, they provided an opportunity to evaluate new treatment options, and indeed the development of treatment strategies in dogs and humans has mutually benefited both species [ 164 ]. Although canines have been instrumental for OS research, it is worth noting that OS in dogs occurs exclusively in old age, not entirely mimicking the human disease that peaks in adolescence [ 107 ].…”

The Role of Pre-Clinical 3-Dimensional Models of Osteosarcoma

“…Initial rodent models for OS were developed by exposing the tibia to chemical and radioactive carcinogens, which produced histologically accurate tumours and can still be utilised to represent the DNA damage effect on pathogenesis [ 27 ]. Despite the success in generating this model, it does not represent the sporadic and spontaneous generation of this disease in humans and is not routinely used to represent the aetiology of OS [ 10 ]. The establishment of immunocompromised mice allowed for the inoculation of a variety of human OS cell lines; these can be injected subcutaneously, although the inoculation of OS cell lines or cell grafts directly into the femur are considered more therapeutically relevant as subcutaneous injection only allows for ectopic bone formation.…”

“…The introduction of gene targeting technologies allowed for the development of transgenic mice. There are several genetically modified mouse models for OS; most are based on the P53 and Rb mutations [ 10 ]. When mice were generated with mutations in the Rb gene alone, it was found that the Rb gene is essential for normal mouse development, with some strains producing serious defects, making breeding difficult [ 34 ].…”

“…In younger patients, OS most commonly invades the metaphyses of long bones, including the proximal tibia, humerus and distal femur [ 9 ]. These tumours have the ability to produce metastases that translocate and form most frequently in the lungs [ 10 ]. Five year event free survival rates for OS are reported to be approximately 50%, but are much lower in patients with metastatic disease, who have a 5 year event free survival rate of 30% [ 11 ].…”