Figure 6.
Different dose-response parameters capture cell line to cell line variation at different dose regimes. (a) Variations of the predictive value (coefficient of Pearson correlation with relative viability) for each of the three key dose-response parameters (IC50, Emax and AUC) with dose for three selected drugs, 17-AAG, carboplatin and doxorubicin. (b) Predictive value of different dose-response parameters for drug sensitivity is a function of the clinical concentration of drug. Dose-response parameters corresponding to the most significant correlation (as evaluated by P value) with cellular response (i.e. relative viability) at doses spanning a range from the most sensitive cell line’s IC50 to the highest tested dose for each drug are shown. For example for the mTOR inhibitor PP242, EC50 (denoted by green bar) is the parameter with the highest correlation with relative viability when cell lines are exposed to drug concentrations around 10−4 times the maximal tested dose (i.e. 10−5×10−4.3 M 0.5 nM). At a 100-fold higher concentration (i.e. 10−3×10−4.3 M ≈ 50 nM), AUC (denoted by red bar) shows the strongest correlation with relative viability.