Abstract 1752: Search for effective therapies for canine and human osteosarcoma using novel therapeutic agents
2014; American Association for Cancer Research; Volume: 74; Issue: 19_Supplement Linguagem: Inglês
10.1158/1538-7445.am2014-1752
ISSN1538-7445
AutoresYa-Ting Yang, Ewa Bartczak, Vilma Yuzbasiyan‐Gurkan,
Tópico(s)Veterinary Oncology Research
ResumoAbstract Osteosarcoma (OS) is the most common primary bone tumor of both humans and dogs. Despite advances in treatment of other cancers, the survival rates for OS have stagnated for the past decades. Therefore, there is a great need to identify novel and effective treatments. Several classes of novel small molecules with anti-tumor activities have become available in the last few years. Among these are tyrosine kinase inhibitors (TKIs) which are a class of potential anti-tumor medications that are able to inhibit kinase activity of many receptor tyrosine kinases. Another class of molecules target inhibition of the proteasome which induces cell death through various mechanisms. We hypothesized that one or more of such drugs would be effective against canine and human OS cell lines. Our preliminary data identified three TKIs (sunitinib, sorafenib, gefitinib), and a proteasome inhibitor (bortezomib) as having good growth inhibition effects in 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. We then determined the exact IC50 concentration of each drug, capable of inhibiting proliferation by 50%. The IC50 values of bortezomib range from 0.01 to 0.22 μM and the values for sorafenib were from 6 to nearly 9 μM across different cell lines tested, which were all within or close to achievable plasma concentration and tolerable levels. In addition, sunitinib, sorafenib, and bortezomib were shown to decrease cell migration ability in the wound healing assay. With the promising results from in vitro studies, these small molecule inhibitors are good candidates for further evaluation in treating human and canine OS. Citation Format: Yating Yang, Ewa Bartczak, Vilma Yuzbasiyan-Gurkan. Search for effective therapies for canine and human osteosarcoma using novel therapeutic agents. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1752. doi:10.1158/1538-7445.AM2014-1752
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