Supplementary Figure 4 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism

Supplemental Figure 4. Drug interactions in CHOP using MuSyC method to distinguish potency and efficacy shifts. A) The MuSyC method analyzes drug combination effects to distinguish between shifts in potency and shifts in efficacy. Shifts in potency from the Bliss model (orange) to observed data (blue) are represented by parameter A, where positive values indicate superior potency and negative values indicate inferior potency. Changes in efficacy are represented by parameter B, where positive values indicate greater inhibition, and negative values indicate less inhibition. B) Example of method for a drug combination with lower efficacy than predicted by the Bliss model. The interaction model (red) is fit from the Bliss model to the experimental data across the length of the curve. The quadrant plot shows the A and B parameters that confer the best fit determined by sum of squares errors. Stronger fits are colored darker blue and the best fit is marked in red. Data shows drug combination CHOP in SU-DHL-1 T-Cell lymphoma cell line, n=8. C) Example of method for a drug combination with higher efficacy than Bliss model predicts. Data shows drug combination leuocorovin-fluorouracil-irinotecan in Lovo Colorectal cancer cell line, n=8. D) Shifts in potency and efficacy for all 11 combinations of agents in CHOP, for each of four Peripheral T-Cell Lymphoma cell lines: KHYG-1, SU-DHL-1, Ki-JK, MTA. Yellow region marks a two-fold difference in potency or efficacy compared with the ‘no interaction’ null hypothesis. Error bars are 95% confidence intervals, n=8.