LAUSR

Omacetaxine mepesuccinate (OMX), also known as homoharringtonine, is a protein translation inhibitor approved for use in chronic myeloid leukemia. Recent studies suggest OMX may be effective against other cancer types with high rates of protein translation, and may be successful against protein targets that are difficult to inhibit by reducing their translation rates. Using both canine and human osteosarcoma (OS) cell lines, we have investigated the efficacy of OMX against osteosarcoma and expression of c-MYC. OMX provides significant growth inhibition of OS cells with IC50 values in the low nanomolar range. OMX also reduces migration and invasion capabilities of OS cells. Strikingly, we observed reduction in levels of c-MYC protein in most canine and human OS cell lines after OMX exposure. This reduction was both dose and time dependent. We also investigated the efficacy of OMX against OS in an orthotopic mouse OS model. OMX is a promising candidate for treatment of OS in both dogs and humans, and potentially additional cancers dependent on c-MYC. Citation Format: Kristen B. Farrell, Douglas H. Thamm. Omacetaxine reduces c-MYC expression and demonstrates antitumor effects in osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6233.