The landscape of metabolic pathway dependencies in cancer cell lines
Fig 5
Pharmacological PDEA reveals consistent metabolic pathway vulnerabilities in Adherent RPMI cell lines.
A) Pharmacological PDEA (S4 Fig) was performed on 1,390 anti-cancer drugs from the PRISM database. Drugs were mapped to metabolic pathways by their annotated target(s) and then the enrichment of these metabolic pathway inhibitors was analyzed in the rank list of drug sensitivity-metabolic pathway activity correlation coefficients. Hierarchical clustering was performed on NES values, and results with FDR < 0.25 are plotted. Dots are colored according to the NES and sized according to the -log10 FDR. Dots with black outline correspond to results shown in panels B-C and F. B-C) Increased Alanine, Aspartate, and Glutamate metabolism (hsa00250) correlates with increased response to inhibitors of terpenoid backbone biosynthesis. In contrast, decreased Pentose Phosphate Pathway metabolism correlates with increased response to inhibitors of Folate Biosynthesis (hsa00790). D-E) Inhibitors of Folate Biosynthesis (hsa00790) are more effective when overall metabolic pathway expression is low, whereas inhibitors of Ascorbate and Aldarate Metabolism (hsa00053) are more effective when overall metabolic pathway expression is high. F) Representative mountain plots and the drug(s) driving enrichment of metabolic pathway activities that strongly correlate with response to inhibitors of Ascorbate and Aldarate metabolism are shown.