Abstract 3689: Comparative oncology drug discovery for Osteosarcoma in dogs and humans

Introduction: The purpose of this study was to identify FDA approved drugs that initiate cell death or growth arrest in canine and human osteosarcoma (OS) cell lines in vitro followed by confirmation of anticancer activity in these cell lines. The ultimate objective of this comparative oncology project is to identify promising agents for the treatment of osteosarcoma in dogs and humans, a disease in which survival rates have remained low and stagnant for the last three decades. Procedures: A library of 2,328 FDA approved drugs was screened for activity in 2 canine and 2 human OS cell lines, as well as in 1 corresponding normal cell line. Cell viability was measure using the Cell Titer-Glo™ Luminescent Cell Viability Assay (Promega). FDA approved drugs meeting pre-determined screening criteria for activity, selectivity, and potency were selected for confirmatory studies. Effects on cell proliferation were confirmed using cell counting using trypan blue exclusion performed over a 10 day period. Effects on cell cycle and apoptosis were performed using propidium iodide staining and flow cytometry. Summary: Nine FDA approved drugs were identified based on activity and selectivity. Auranofin, a FDA approved rheumatoid arthritis agent, was selected for cell proliferation and cell cycle evaluation due to its IC50 value in control cells in comparison to OS cell lines. Auranofin displayed cytostatic effects in canine and human OS cell lines at low doses and drugs appeared to induce G2 arrest in treated cells. Conclusions: Auranofin is an FDA approved drug that demonstrates promising, selective anticancer activity in canine and human OS cell lines. The next steps are to determine whether this agent possesses additive or synergistic activity in combination with anticancer agents that have already demonstrated clinical activity in dogs and humans with OS. In vivo preclinical proof of concept will be determined in mouse xenograft studies and dogs with spontaneous OS for promising drug combinations. Subsequently, we hope to rapidly translate preclinical proof of concept findings to human OS patients. Citation Format: Joy M. Fulbright, Kathleen Neville, Melinda Broward, Tyce A. Bruns, Anuradha Roy, Peter McDonald, Megan Ottomeyer, Douglas H. Thamm, Tomoo Iwakuma. Comparative oncology drug discovery for Osteosarcoma in dogs and humans. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3689. doi:10.1158/1538-7445.AM2015-3689