Figure 3

Retrospective analysis evaluates CDKN2A mutation – drug response association by in silico modeling. Using simulation modeling, we tested the role of the tumor-suppressor protein CDKN2A on sensitivity to different inhibitors and compared these predictions to those reported in the Garnett study. A, Cells expressing mutant CDKN2A and their wild-type variants were simulated in the in silico tumor model for four lines – BxPC3, H1437, H1650 and SW48. CDKN2A mutation increased sensitivity of cells to erlotinib when compared to wild-type CDKN2A. B, Cells with mutant CDKN2A were more sensitive to dasatinib than cells with wild-type CDKN2A (A549, BxPC3, HCT116 and H460). C, COLO205, HT29, H1437 and SW48 cell lines with mutant CDKN2A were sensitive to bortezomib more than cells expressing wild-type variants. D, CDKN2A mutant cells BxPC3, H1437, H1975 and HT29 also showed higher sensitivity to CDK4-Cyclin D1 inhibitor PD0332991 over the CDKN2A WT variants.