Fig. 3: The used multiplicative survival equation can provide a false positive outcome when a 0.8 threshold is applied.
From: Challenges to determine synergistic drug interactions in mice
A Matrix showing the estimated additive survival based on the fractional product (left panel) and the corresponding synergy as calculated by the mutual non-exclusive median-effect formula of Chou and Talalay (right panel) using 0.8 as a synergy threshold. This shows that a false positive synergistic outcome can be obtained when high efficacies are reached by both drugs (>50% viability loss). This warrants the use of this method in the context of high efficacies. B 3D plot of the calculated mutual non-exclusive median effects using the equation of Chou and Talalay as based on the theoretical fractional product (gray and blue surface). Experimental data that follow an additive pattern are shown in purple. Experimental combinations that show values beyond the expected theoretical additivity and hence, are considered synergistic despite the flaw in the Chou and Talalay equation, are shown in bright colors: MDA-MD231 treated with AZ628 and Gemcitabine (AZD + GEM representing 4 time points shown in dark red), MDA-MD231 treated with Thapsigargin and AZ628 (AZD + THAP representing 2 time points shown in red), CHL1-FM treated with Gemcitabine and CGP-082996 (GEM + GCP representing 3 time points shown in green), U87MG treated with Docetaxel and GNE-317 (DOC + GNE representing 1 time point shown in blue). P-values represent a two-sided student t-test of the measured luminescence (tumor volume) of the drug combination versus the predicted effect calculated from the fractional product according to Webb17.
