Fig. 7 | Nature Communications

Fig. 7

From: Pan-cancer analysis of transcriptional metabolic dysregulation using The Cancer Genome Atlas

Fig. 7

Basal-like BRCA cells are more sensitive to citric acid cycle targeting than luminal-like BRCA cells. a The Sanger Database of Genomics of Drug Sensitivity in Cancer shows a statistically significant difference in sensitivity to phenformin between basal and luminal-like breast cancer cell lines. b Hierarchical clustering of all TCGA cancer cohorts revealed two major groups of citric acid cycle gene expression: highly up-regulated (purple) and highly down-regulated (orange). c Analysis of sensitivity to phenformin in cell lines of different cancer types comparing those with citric acid cycle gene up-regulation (purple) and down-regulation (orange). d DeSigN was then used based on the citric acid cycle signature to determine drugs that would preferentially target cells with CAC dysregulation and identified 11 drugs, most of which had significant differences in drug sensitivity between luminal and basal breast cell lines. e Data downloaded for cell lines with TCGA classifications that were utilized in this analysis revealed those cancer types with increased numbers of up-regulated genes (purple) were in fact more sensitive (lie to the left of the mean IC50 line) than those with more down-regulated genes (orange). f There is a statistically significant difference in the IC50s between basal breast cancer cell lines and luminal cell lines, indicating that basal cell lines are more sensitive, as predicted. *Error bars represent s.d.

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