Abstract 2949: Synergistic effects of tyrosine kinase inhibitors and conventional chemotherapeutics on canine and human osteosarcoma cells

Osteosarcoma (OS) 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 treatment of other cancers, the overall survival rates for OS have stagnated for the past decades. Therefore, there is a great need to identify novel and effective treatments. In the past few years, several classes of novel small molecules with anti-tumor activities have become available. Among them, we selected tyrosine kinase inhibitors (TKIs) with potential anti-tumor medications to evaluate the effects of treating OS. In our previous studies, two TKIs (sunitinib and sorafenib) showed good growth inhibition effects at low concentrations on three canine OS cell lines (D17, Abrams, and Gracie) and two human OS cell lines (SAOS2 and U2OS) in a series of drug screening assay. In addition to viability, migration, and invasion ability of OS cells were decreased by these two TKIs. Furthermore, we investigated the effect of combing one of the TKIs with current chemotherapeutics for OS. We determined the combination index to assess whether sorafenib and sunitinib have synergistic effects with conventional chemotherapeutics including cisplatin, carboplatin, or doxorubicin. Data from our cell lines point to synergistic effects of sorafenib combined with doxorubicin, but not when combined with cisplatin or carboplatin in both human and canine OS. Combination studies with sunitinib are ongoing. Based on current findings, clinical trials using 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 initiation of clinical trials in humans. Citation Format: Ya-Ting Yang, Vilma Yuzbasiyan-Gurkan. Synergistic effects of tyrosine kinase inhibitors and conventional chemotherapeutics on canine and human osteosarcoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2949.