Figure 3
From: Drug-based perturbation screen uncovers synergistic drug combinations in Burkitt lymphoma
Landscape of synergistic drug combinations in BL. (A) Heatmap shows clustering based on CI across cell lines (n = 15). We observed cell lines with dominant combination effects (BJAB and BL-60), as well as drug combinations leading to synergistic effects across cell lines, i.e. deforolimus and idelalisib or SNS-032 and OTX015. Multiple combinations showed cell line dependent effects where combinations lead to both synergistic and antagonistic effects (e.g. Salina, Séraphine). CI values for Gumbus, BL-7 and BL-41 were excluded from the analysis due to high toxicity of the combination drugs, which resulted in unreliable determination of drug interactions. (B) Bar plot summarizes median CIs across 18 cell lines for all 96 combinations tested in the combination assay reveal synergistic combinations. Dashed lines correspond to the definitions of drug interaction (<0.85 = synergistic; >1.15 = antagonistic). Error bars indicate interquartile range. The analysis yields few antagonistic and 20 synergistic combinations. Most synergistic combinations were identified for OTX015. (C) Median dose-response curves for combinations with the lowest CI: MK-2206 with ibrutinib; MK-2206 with idelalisib and SNS-032 with OTX015 (n = 18 cell lines). The marked area between the combination curve (green) and single agent curves (blue, red) indicates the drug interaction.
