College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Department of Microbiology & Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Int J Mol Sci. 2022 Aug 19;23(16):9345. doi: 10.3390/ijms23169345.
Osteosarcoma (OSA) is the most common bone tumor in both humans and dogs and has a nearly ten-fold higher incidence in dogs than humans. Despite advances in the treatment of other cancers, the overall survival rates for OSA have stagnated for the past four decades. Therefore, there is a great need to identify novel and effective treatments. We screened a series of tyrosine kinase inhibitors and selected sorafenib, a multi-kinase inhibitor, for further evaluation alone and in combination with cisplatin, carboplatin, and doxorubicin on canine and human OSA cell lines. Our data point to synergistic effects when sorafenib is combined with doxorubicin, but not when combined with cisplatin or carboplatin, in both human and canine OSA. Based on current findings, clinical trials using a combination of doxorubicin and sorafenib in proof-of-concept studies in dogs are warranted. These studies can be carried out relatively quickly in dogs where case load is high and, in turn, provide useful data for the initiation of clinical trials in humans.
骨肉瘤（OSA）是人类和犬类中最常见的骨肿瘤，犬类的发病率比人类高近十倍。尽管其他癌症的治疗取得了进展，但过去四十年来，OSA 的总体生存率一直停滞不前。因此，非常有必要寻找新的有效治疗方法。我们筛选了一系列酪氨酸激酶抑制剂，并选择多激酶抑制剂索拉非尼进行进一步评估，分别评估了其单独使用以及与顺铂、卡铂和阿霉素联合使用对犬和人骨肉瘤细胞系的效果。我们的数据表明，索拉非尼与阿霉素联合使用具有协同作用，但与顺铂或卡铂联合使用时则没有这种作用，无论是在人骨肉瘤还是犬骨肉瘤中都是如此。基于目前的研究结果，在狗身上进行联合使用阿霉素和索拉非尼的概念验证研究的临床试验是合理的。这些研究可以在狗身上相对较快地进行，因为狗的病例数较多，从而为在人类中启动临床试验提供有用的数据。
