Abstract 5590: Screening of pediatric and adult sarcoma cell lines reveals novel patterns of sensitivity toward approved oncology drugs and investigational agents.

Abstract

Abstract Sarcomas represent a heterogeneous group of neglected cancers with significant unmet medical need. To date, large-scale screening of compounds for activity against sarcomas has not been carried out in any systematic fashion to enable drug discovery. Our laboratory has compiled a panel of > 85 human pediatric and adult sarcoma cell lines, a tumor type not represented in the NCI60, and has carried out a high throughput screen of approximately 60 of these lines against the Approved Oncology Drugs (AOD) and Investigational Agents libraries, using inhibition of proliferation as an endpoint. The AOD library is comprised of 93 FDA-approved anticancer agents, and is available from The NCI/DTP Open Chemical Repository. The Investigational Agents library includes about 350 small molecules of interest. The compounds were screened for inhibition of cell proliferation in 9-point concentration response, starting at 10 uM and diluting by half-logs. The cells were cultured in 384-well plates for 24 hrs, at which time compounds were added with a final DMSO concentration of 0.25%. Viability was determined after 96 hrs of exposure using Alamar Blue. The % viability was determined relative to a vehicle-treated control, and this value was plotted relative to compound concentration to determine the EC50. The Ewing sarcoma lines (19) were unexpectedly more sensitive to pemetrexed, cabazitaxel, and floxuridine, and were, as expected, sensitive to topoisomerase 1 inhibitors relative to other sarcomas and to historical NCI60 data. Synovial sarcoma lines were sensitive to vinorelbine, vandetinib, and gemcitabine relative to other sarcomas. Further analyses and findings from the data will be presented. Funded by NCI Contract no. HHSN261200800001E. Citation Format: E. Michael August, Rene Delosh, Julie Laudeman, Chad Ogle, Russell Reinhart, Michael Selby, Thomas Silvers, Joel Morris, Beverly A. Teicher. Screening of pediatric and adult sarcoma cell lines reveals novel patterns of sensitivity toward approved oncology drugs and investigational agents. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5590. doi:10.1158/1538-7445.AM2013-5590