Supplementary Figure 5 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism

Supplemental Figure 5. Short-term adaptive resistance does not affect sequential treatments. MTA cell cultures were treated for 3 days with either 4-H-cyclophosphamide, doxorubicin, vincristine, or no treatment (control). Drugs were administered at concentrations producing 50% growth inhibition. Following treatment, cultures were washed of drug and recovered in drug-free media for 4 days. After recovery, dose responses were measured for 3-day treatments with 4-H-cyclophosphamide, doxorubicin, vincristine, prednisolone, and the CHOP combination. Figure 2a presents the results of these experiments with relative drug sensitivity quantified as ‘Area Over the Curve’ (AOC) (area between the dose-response curve and the line y=100% relative viability). Pre-treated cultures were not more resistant to chemotherapy than control cultures. Error bars represent 95% confidence intervals, n=8.