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Fig. 5 | Journal of Experimental & Clinical Cancer Research

Fig. 5

From: Auranofin repurposing for lung and pancreatic cancer: low CA12 expression as a marker of sensitivity in patient-derived organoids, with potentiated efficacy by AKT inhibition

Fig. 5

Auranofin drug combination strategies. A Overview of the 11 therapeutics that were tested in combination with Auranofin. B Heatmap showing the normalized Area Over the Curve (AOC) values of the fitted Normalised Organoid Growth Rate (NOGR) dose–response curves for each therapy and organoid line. C Bubble plot showing the mean ZIP synergy score (bubble size) and combination sensitivity score (CSS, colored heatmap) for each drug and organoid line. D Bubble plot showing the ZIP synergy score (bubble size) and NOGR (colored heatmap) for a concentration range of MK2206 and 909 nM Auranofin for each organoid line. Bubble size: small = ZIP < -10 indicating antagonism; medium = -10 < ZIP < 10 indicating an additive effect; large = ZIP > 10 indicating synergism. NOGR between 1 and 0 indicates a cytostatic response, NOGR < 0 indicates a cytotoxic response. The resistant, intermediate and sensitive groups refer to the Auranofin response classification. E Representative images of organoids (PDAC_044) treated with vehicle (DMSO), 416 nM MK2206, 909 nM Auranofin or the combination for 120 h. Magenta = label-free organoid segmentation by Orbits®; Green = raw cytotox green signal; LU_46N = normal pulmonary organoid; PDAC_044 = pancreatic ductal adenocarcinoma organoid

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