Figure 3 from Screening FDA-Approved Oncology Drugs with Three-Dimensional Spheroids Identifies Romidepsin as a Therapeutic Candidate for Osteosarcoma

<p>The HDI romidepsin is most promising of the 13 FDA-approved oncology drugs in the secondary screen. All heatmaps in this figure are sorted by the overall row means shown in the first column of each heatmap. Dark blue indicates highest values (most favorable), dark red the lowest values (least favorable), and white is set at the median of the row means. <b>A</b> and <b>B,</b> Ratios of Cmax/sarcosphere (Sarco) ED<sub>50</sub> with and without MAP reflect potency at clinically achievable concentrations. Cmax and ED<sub>50</sub>s are shown in Supplementary Table S3 and Supplementary Fig. S1. ED<sub>50</sub>s were determined for sarcospheres derived from LM7, 143B, and MG63.3-GFP cell lines in <i>N</i> = 3 independent dose–response experiments with each drug. Each experiment included at least three sarcospheres per group. <b>C</b> and <b>D,</b> Synergy scores in combination with MAP. Highest synergy scores at concentrations less than Cmax were calculated for each drug using the Bliss and Loewe models of additivity from the data shown in <b>E–G</b> and Supplementary Figs. S2–S4. <b>E–G,</b> Romidepsin dose responses with and without MAP for sarcospheres derived from LM7, 143B, and MG63.3-GFP cell lines. Solid black lines indicate romidepsin dose responses without MAP, and colored lines indicate romidepsin dose response with MAP. Dotted lines indicate Bliss prediction of perfect additivity. Bar graphs show synergy scores at each individual drug concentration.</p>