<i>In vitro</i> drug response waterfall plots of 38 organoid cultures show individual patterns of resistance and sensitivity.

IC50values for 38 in vitro models were determined with a semi-automated drug response assay platform. The lower and upper assay cutoffs were 0.003 μM and 60 μM. Drug efficacy (Emax) was included as additional measure of response, indicated with light grey to black boxes according to percent efficacy above the waterfall plot. The genotype of each culture according to panel sequencing is color-coded according to the legend given at the bottom of the figure. Area (grey) of achievable steady state in vivo plasma concentrations (css) are given in μM and indicated with grey dotted lines. (A-C) IC50values for small molecules gefitinib, afatinib and sapitinib, targeting the ERBB receptor(s) ERBB1/EGFR, ERBB2/Her2, ERBB3 and ERBB4. (D) Inhibition at the level of MEK1/2 with selumetinib. (E) Response to the multikinase inhibitor regorafenib. (F) Treatment with the mTORC1/2 inhibitor BI-860585. The BRAFG466Rand BRAFG466Vmutations in tumors OT170 and OT327, respectively, are not included in the figure, as their gene products are considered kinase-dead [77].