Abstract 1354: Developing 384-well and 1536-well cell growth inhibition assay workflow for screening drug-drug combination in tumor cell lines

Abstract

Abstract Drug combination has been widely used in treating the most debilitating diseases such as cancer. The ideal drug-drug combination will broaden and/or deepen therapeutic efficacy while overcoming resistance and unwanted off-target effects. We have developed a 384-well combination compound plating method in 8×7 format (8 dilutions of Drug A and 7 dilutions of Drug B), and screened a number of compound pairs that showed synergistic effect in inhibiting tumor cell growth in either suspension or solid tumor lines. Compound vehicle DMSO was used as negative control and puromycin treatment as positive control for calculating% inhibition, and both HSA and Bliss independence synergy models were applied for calculating synergy scores. As 384-well 8×7 format contains one compound pair per plate, we aimed to increase the throughput by developing 384-well 5×5 format (5 dilutions of Drug A and 5 dilutions of Drug B) which contains 3 drug pairs per plate, and 1536-well 8×7 and 5×5 format which contains 4 and 12 drug pairs per plate, respectively. We compared EC50s and synergy scores generated from 384-well and 1536-well with both 8×7 and 5×5 formats, single agent EC50s within combination pairs were generally within 3 fold difference and synergy scores are largely consistent. Therefore, we have validated and enabled higher throughput drug-drug combination screen by using 384-well 5×5, 1536-well 8×7, or 5×5 format. The high-throughput method presented here can be readily adopted for combination studies in other disease areas. Citation Format: Yvonne Li, Mike Ma, Julie Chan, Yang Tian, Nikos Pagratis, Derek Stonich, Victor Chen, Louis Zhang, Mark Kenney. Developing 384-well and 1536-well cell growth inhibition assay workflow for screening drug-drug combination in tumor cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1354.