FIGURE 2 from Multicellular Complex Tumor Spheroid Response to DNA Repair Inhibitors in Combination with DNA-damaging Drugs

<p>Combination of PARP inhibitors and temozolomide. <b>A,</b> Mean Bliss matrix scores were calculated from each combination's concentration matrix [(5 concentrations of drug A) × (6 concentrations of drug B) = (30 combination concentrations)]. The scores (<i>n</i> = 546) are graphed for all combinations of DNA-damaging drugs with DNA repair inhibitors tested (<i>n</i> = 21) in all complex tumor spheroid models (<i>n</i> = 26). <b>B,</b> The same data shown in A) but combinations of the DNA-damaging drug temozolomide with either PARP inhibitor olaparib or talazoparib are highlighted in blue (<i>n</i> = 52), whereas all other combinations are shown in light gray. <b>C,</b> A scatter plot of the mean Bliss matrix scores from the temozolomide combinations with olaparib and talazoparib (Pearson <i>r</i> = 0.73, two-tailed <i>P</i> < 0.0001). Concentration–response curves (top, mean ± SD, <i>n</i> = 4 technical replicates) from combinations of temozolomide with either olaparib (<b>D</b>) or talazoparib (<b>E</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): VA-ES-VJ (epithelioid sarcoma), SYO-1 (synovial sarcoma), 287954-098-R-J1 (Ewing sarcoma), 349418-098-R (NSCLC), and DMS 114 (SCLC).</p>