A pan-cancer screen identifies drug combination benefit in cancer cell lines at the individual and population level

• DOI: 10.1016/j.xcrm.2024.101687
• Publication Date: 2024-08-20T14:49:53Z
• Authors: Daniel J. Vis; Patricia Jaaks; Nanne Aben; Elizabeth A. Coker; Syd Barthorpe; Alexandra Beck; Caitlin Hall; James Hall; Howard Lightfoot; Ermira Lleshi; Tatiana Mironenko; Laura Richardson; Charlotte Tolley; Mathew J. Garnett; Lodewyk F.A. Wessels
• Keywords: BLISS; Cancer cell lines; Combination therapy

Combining drugs can enhance their clinical efficacy, but the number of possible combinations and inter-tumor heterogeneity make identifying effective challenging, while existing approaches often overlook clinically relevant activity. We screen one largest cell line panels (N = 757) with 51 identify responses at level individual lines tissue populations. establish three response classes to model cellular effects beyond monotherapy: synergy, Bliss additivity, independent drug action (IDA). Synergy is rare (11% responses) frequently efficacious (>50% viability reduction), whereas IDA are more frequent less efficacious. introduce "efficacious combination benefit" (ECB) describe high-efficacy classified as either Bliss, or IDA. ECB biomarkers in vitro show that predicts patient-derived xenografts better than synergy alone. Our work here provides a valuable resource framework for preclinical evaluation development treatments.