Fig. 7.

Combining FDA-approved compounds induces synergy in reducing GBM cell proliferation. L1000 profiling was performed for 83 FDA-approved compounds. a Compounds were clustered according to the transcriptional profile they induce in all cancer cells. Group 1, shaded in green, contains imatinib; Group 2, shaded in orange, contains mitoxantrone, and Group 3, shaded in red, contains gemcitabine. b Compounds were ranked based on concordance to gemcitabine and discordance from signature of the mean of the PDX GBM cell lines and two compounds were selected to test for proof of concept: imatinib and mitoxantrone. Orthogonality score was computed and the Loewes combination index was calculated in PDX GBM76 cells. c, d The reduced cell proliferation responses to imatinib and mitoxantrone in monotherapy for 4 cell lines were plotted against the cell line-specific discordance scores for imatinib (c) or mitoxantrone (d). e, f Combinations were tested in PDX GBM76 cells. Synergy was calculated using the Loewe additive model and a normalized isobologram was plotted to visualize synergy for each combination. Source data can be found in the Source Data file, Supplementary Data 6, under tab Fig. 7