Figure 7 from Screening FDA-Approved Oncology Drugs with Three-Dimensional Spheroids Identifies Romidepsin as a Therapeutic Candidate for Osteosarcoma

<p>Sarcospheres from a subset of patients are sensitive to romidepsin. Metabolic activity of sarcospheres from 18 human (<b>A</b>) and 10 canine (<b>B</b>) patients was measured after exposure for 48 hours to the indicated concentrations of romidepsin. Black curves represent sensitive subset of patients with ED<sub>50</sub>s <70 nmol/L. Gray curves represent resistant subset, defined as ED<sub>50</sub> >1,000 nmol/L. Each curve represents the mean of at least <i>n</i> = 3 independent experiments with sarcospheres from an individual patient sample. Each experiment included six sarcospheres at each of the indicated doses. Asterisks (*) indicate dose groups (100 and 1,000 nmol/L) that are significantly different (<i>P</i> < 0.05) from the vehicle-treated group for all sensitive samples based on one-way ANOVA with Dunnett multiple comparisons tests. <b>C,</b> Diameters of human patient–derived sarcospheres were measured every 2 hours during exposure to the indicated concentrations of romidepsin or vehicle by the Incucyte S3 Live Cell Analysis System (Sartorius). Each symbol represents mean ± SEM of <i>N</i> = 6 patients (two romidepsin sensitive and four romidepsin resistant). Sarcospheres from each patient were analyzed in 1–3 independent experiments. Each experiment included 3–6 sarcospheres per dose group. <b>D,</b> Representative images of romidepsin-sensitive sarcospheres from experiments depicted in <b>C</b>. Yellow size bars in lower left of images show 600 mm. Time stamp is shown in lower right of each image. <b>E,</b> Representative images from romidepsin-resistant patients from experiments depicted in <b>C</b>. Yellow size bars in lower left of images show 800 mm. Time stamp is shown in lower right of each image.</p>