Table 2.

Sensitivity to targeted therapies correlates with the corresponding targeted alteration in vitro

AlterationTissueDrugGDSC WilcoxonCCLE Wilcoxon
BCR-ABLBloodImatinib0.0008NA
BloodNilotinib0.001NA
BloodDasatinib0.001NA
KIT CNVAll tissuesImatinib0.051NA
FLT3 MUTATIONAll tissuesSorafenib0.160.0007
All tissuesSunitinib0.01NA
ERBB2: MUT AMPBreastLapatinib0.0030.01
OvaryLapatinibNAb0.3
LungLapatinibNAb0.35
StomachLapatinibNAb0.047
All tissuesLapatinib0.00020.0003
EGFR: MUT AMPLungErlotinib0.130.02
CNSaErlotinib10.25
All tissuesErlotinib0.041.40E−05
MET: MUT AMPAll tissuesPHA-6657520.370.49
All tissuesPF-23410660.070.15
ALK: MUT AMPAll tissuesPF-23410660.010.54
BRAF: MUT AMPAll tissuesPLX4720<2.2e−16<2.2e−16
SkinPLX47200.0030.027

NOTE: Cell lines across two large in vitro pharmacogenomics databases were separated based on being wild type or mutant for several alterations for which targeted therapy exists. Amplifications in each dataset (Affymetrix SNP 6.0 arrays) were defined according to the protocols in the GDSC (8) and CCLE (9). Data for this analysis were taken directly from the CCLE or GDSC web resources. The significance of mutant cell lines drug sensitivity compared with wild-type cell lines was determined using a Wilcoxon rank-sum test.

  • aFor the GDSC: Glioma, medulloblastoma, neuroblastoma.

  • bIC50 not available in each group.