Fig. 5
From: Subclonal response heterogeneity to define cancer organoid therapeutic sensitivity
Validation of PCO response for clinical prediction. (a) Representative brightfield microscopy from MTB-3 ovarian (Ov) PCOs at baseline and 48 h; scale bar represents 200 μm for each panel. (b) Gaussian distributions for growth at 48 h with respective effect sizes (GΔ) for MTB-3 Ov PCOs treated with gemcitabine 50 μm (24 h, green), paclitaxel 50 nM (48 h, gold) or control (black) as assessed at 48 h. (c) Clinical response from the initial restaging CT scan of subject MTB-3 confirming the disease with enlarging retroperitoneal adenopathy after treatment with single agent gemcitabine on CT imaging. (d) Representative brightfield microscopy for MC7 PCOs treated with control (top panels), or FOLFOX (5-FU 10 μm and oxaliplatin 5 mμ (e) Gaussian distributions of MC7 for Δ diameter over 48 h and respective effect sizes (GΔ) for 5-FU 10 μm (blue), oxaliplatin 5 μm (red), and FOLFOX (violet). (f) Restaging CT scan of MC7 shows partial response after FOLFOX. (g) Experimental sensitivity with clinical outcome or canonical mechanism of resistance labeled by treatment type including chemotherapy (purple), targeted therapy (blue), canonical EGFRi resistance (RASMT or RAFMT, red), and radiation (black) with reported significance by two-sided student t-test. (h,i) Comparison of FOLFOX effect size (GΔ) between PCOs with disease progression after FOLFOX chemotherapy versus subjects without prior drug exposure assessed using two-sided student t-test with prior established sensitivity thresholds (shaded region). (h) Absolute diameter effect size assessed at 48 h for single agent 5-FU (ns), oxaliplatin (ns) and FOLFOX (*p < 0.05) between clinically resistant and unknown cohorts. (i Effect size of growth (percent Δ diameter) tracked from 0 to 48 h for single agent 5-FU (*p < 0.05), oxaliplatin (**p < 0.005) and FOLFOX (***p < 0.0005) between clinically resistant and unknown cohorts. (j) Bar plot of negative predictive value (NPV) and positive predictive value (PPV) for prospectively treated subjects. (k) Receiver operator curve (ROC) in response prediction plotted as false positive rate versus sensitivity with the colored line showing the continuum of effect size (GΔ) for change in diameter and corresponding area under the curve (AUC).
