Abstract 2016: HDAC inhibition significantly reduces primary and lung metastatic osteosarcoma progression

Osteosarcoma (OS) is the most common bone malignancy in adolescents. At the time of initial diagnosis, approximately 15% of the patients present with metastatic disease in lungs. Prognosis for this cohort is grim with 5-year overall survival rates at 30%. Frustratingly, these statistics have changed little over the past three decades, in part due to the lack of progress in identifying effective therapies and difficulty in coordinating robust clinical trials in this relatively rare malignancy. To address this, we previously screened 54 FDA approved drugs against 5 different OS cell lines and identified the histone deacetylase inhibitor (HDAC), panobinostat (Pano) as having potent effects in vitro. Here, we explore whether Panobinostat is effective in preventing multiple stages of OS progression in vivo using the K7M2 and SAOS2LM7 pre-clinical models of the disease. Pano prevents the growth of primary OS and lung metastasis. Mice were intratibially inoculated with K7M2-Luc cells and then treated with vehicle (n=11) or panobinostat (n=10; 10 mg/kg for all in vivo studies). Tumor growth was measured by bioluminescence (RLU). The clinical endpoint was 1x106RLU (IVIS-200). Primary OS growth was significantly slower in the panobinostat treated group (p Citation Format: Niveditha Nerlakanti, Jeremy McGuire, Diana Yu, Damon R. Reed, Conor C. Lynch. HDAC inhibition significantly reduces primary and lung metastatic osteosarcoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2016.