Effective drug combinations identified by pan-cancer cell line screening

A new paper published on Cancer Discovery features the largest cancer drug combination screening ever made on cell lines. Authors tested 109 combinations in more than 750 cancer cell lines, describing three actionable combinations confirmed in vitro and in vivo, with a focus on hematologic cancers and apoptotic targets.

Researchers screened 109 drug combinations of 37 individual drugs and investigational agents across 755 cell lines covering 41 cancer types. Drugs covered diverse targets and mechanisms of action with a particular focus on compounds targeting genome integrity, apoptosis, and the cell cycle, which had potential for broad activity in a pan-tumor panel and which were of interest for clinical development. From more than 68,000 combination:cell line pairs tested, authors aimed to identify candidate combinations with the greatest potential to be taken forward into clinical development. Therefore, they identified combination:cell line pairs with high activity and combination benefit/synergy beyond single-agent activity, with clearly defined patient populations, rationale for tolerability based on tumor type and combination-specific “emergent” biomarkers, and exposures relevant to clinical doses. The majority of the active combinations were active in multiple cancer types: specifically, nineteen combinations were active in more than 50% of cancer types. By using their prioritization framework, researchers identified three active and cancer-type selective top scoring combinations and produced an exceptionally data-rich resource. «Our approach is designed to optimize preclinical interpretation with a focus on actionability. Rather than simply selecting combinations which elicited the greatest synergy, we shortlisted combinations that were highly active, more effective than monotherapy alone, and cancer-type selective. Our study provides a rich resource and identifies actionable combinations as a starting point toward achieving the goal of developing rational combinations to improve treatment options for patients», authors conclude.