A pan-cancer screen identifies drug combination benefit in cancer cell lines

This study, a collaboration between researchers from the Netherlands Cancer Institute, Wellcome Sanger Institute (UK), Delft University of Technology, and Oncode Institute, outlines a comprehensive pan-cancer screening to identify effective drug combinations across diverse cancer cell lines. Screening 51 drug combinations in 757 cell lines, the team classified responses into synergy, Bliss additivity, and independent drug action (IDA), recognizing that effective responses extend beyond traditional synergy.

A key concept introduced is efficacious combination benefit (ECB), which identifies combinations that achieve over 50% cell viability reduction, regardless of interaction type. ECB proved more predictive of response in patient-derived xenografts (PDX) than synergy alone, offering a more robust framework for preclinical evaluation.

Top-performing combinations include:

AZD7762 + Gemcitabine: Effective with high synergy rates in the large intestine, esophagus, and endometrium cells.

Navitoclax + Axitinib: Showed strong synergy in bladder cancer cell lines.

MK-1775 + Cisplatin: Displayed high Bliss efficacy across soft tissue, thyroid, kidney, and nervous system cancers.

Trametinib + LGK974: Demonstrated robust IDA across many tissue types.

Olaparib + Temozolomide: Increased efficacy in bone cancers when stratified by biomarkers.

This collaborative work provides a valuable preclinical framework for exploring drug combinations with high ECB scores across cancer types, guiding future clinical applications based on biomarker-driven selection.

Reference

Vis DJ, Jaaks P, Aben N, Coker EA, Barthorpe S, Beck A, Hall C, Hall J, Lightfoot H, Lleshi E, Mironenko T, Richardson L, Tolley C, Garnett MJ, Wessels LFA. A pan-cancer screen identifies drug combination benefit in cancer cell lines at the individual and population level. Cell Rep Med. 2024 Aug 20;5(8):101687. doi: 10.1016/j.xcrm.2024.101687. PMID: 39168097; PMCID: PMC11384948.