Supplementary Figure 3 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism

Supplemental Figure 3. Analysis of drug pairs, triplets, and quadruplet CHOP confirms antagonistic interactions by the Bliss Independence model. A) Effect of CHOP combination measured at concentrations from 0 to 200% of Csustained, compared with Bliss Independence model computed from monotherapy effects, in four PTCL cell lines: KHYG-1, Ki-JK, MTA, SU-DHL-1. Blue shading represents 95% confidence interval (n=8 replicates). B) Relationship between observed cell viability, and predicted viability from Bliss Independence model, for all possible pairs, triplets, and quadruplets of drugs in CHOP across four PTCL cell lines (n=237 points across concentration range up to 500% Csustained; each point is an average of 8 measurements). All combinations containing antagonistic pairs CH or HO are colored in blue; all other combinations in red. Lines of best fit show that, as a group, combinations containing the drug pairs CH or HO (blue line) are antagonistic compared with the Bliss independence model (black line) (P = 6×10-34, Student’s t-test, n=117), and also more antagonistic than all combinations without CH or HO (red line) (P = 3×10-14, Student’s t-test, n=237). Overall, all CHOP measurements (blue and red combined) are antagonistic compared with the Bliss independence model (black line), with an average slope of 0.79 (P = 7×10-35, Student’s t-test, n=237). C) Histogram depicting the difference in observed and expected log-kills (-log10(relative viability) for all interactions involving CH or HO (blue), and all remaining interactions (red)).