FIGURE 3 from Multicellular Complex Tumor Spheroid Response to DNA Repair Inhibitors in Combination with DNA-damaging Drugs

<p>Combination of AZD-1390 and topotecan or trabectedin. <b>A,</b> Mean Bliss matrix scores (<i>n</i> = 546) were calculated from the concentration matrix [(5 concentrations of drug A) × (6 concentrations of drug B) = (30 combination concentrations)] of each combination tested (<i>n</i> = 21) in all complex tumor spheroid models (<i>n</i> = 26). The mean Bliss matrix scores are highlighted from combinations of the ATM inhibitor AZD-1390 with DNA-damaging drugs topotecan or trabectedin (<i>n</i> = 52, orange), whereas the scores from all other combinations are shown in light gray. <b>B,</b> A scatter plot of the mean Bliss matrix scores from the AZD-1390 combinations with topotecan and trabectedin (Pearson <i>r</i> = 0.77, two-tailed <i>P</i> < 0.0001). Concentration–response curves (top, mean ± SD, <i>n</i> = 4 technical replicates) from combinations of AZD-1390 with either topotecan (<b>C</b>) or trabectedin (<b>D</b>) and corresponding mean Bliss score plots (bottom, <i>n</i> = 4 technical replicates) showing the scores from each combination's concentration matrix and colored as a heat map (blue indicates synergy; yellow indicates additivity; red indicates antagonism). Data are shown for complex tumor spheroids grown with the malignant cell lines (from left): G-401 (rhabdoid tumor), NCI-H841 (SCLC), 287954-098-R-J1 (Ewing sarcoma), ASPS-1 (alveolar soft part sarcoma), and DMS 114 (SCLC).</p>