Figure 5.

CRC PDO models with SFAB- (SMAD4, FBXW7, ARID1A, or BMPR2) signature are sensitive to MEK inhibition. (A) Waterfall plots of IC₅₀ values of CRC PDO models with known SMAD4 status tested with MEK-inhibitors cobimetinib, trametinib, and selumetinib. PDO models with IC₅₀ values below c_max are defined as sensitive and PDO models with IC₅₀ values above c_max are defined as resistant. (Orange bars: PDOs harboring pathogenic mutations in SMAD4, FBXW7, ARID1A, or BMPR2; gray bars: PDOs harboring non-pathogenic or no mutations in SMAD4, FBXW7, ARID1A, or BMPR2). (B) Contingency analysis of the MEK-inhibitors cobimetinib, trametinib, and selumetinib for sensitive and resistant models (n = 62). All calculations were performed on technical replicates of two biological samples each (See also Table S2). SMAD4 = mothers against decapentaplegic homolog 4, FBXW7 = F-box/WD repeat-containing protein 7, ARID1A = AT-rich interactive domain-containing protein 1A, BMPR2 = Bone morphogenetic protein receptor type II.