Fig. 7: Identification of non-genetic MET upregulation as a drug target.

a Clinical course of patient PID038. See Supplementary patient case PID038 for details. b PCY-based cellular and morphological sample composition over time. c Comparison of genomic profile between tissue at diagnosis (solid tumor biopsy) and after relapse to osimertinib (FB287) measured by FoundationOne CDx. d PCY-based ex vivo responses of the MSE sample at relapse to osimertinib (FB287) All drugs with significant on-target effects (RCF > 0, p < 0.01) are shown, as well as the previous treatment osimertinib. Exact P values (two-sided Student’s t test, no adjustment for multiple testing) per drug are provided in the Source Data. Drugs highlighted in red target MET. e Comparison of gene expression profiles in FACS-purified tumor cells between FB133 (diagnosis) and FB295 (relapse). MET expression strongly increased in the relapse sample. f Immunohistochemistry against cMET at diagnosis (top, cMET intensity 2+ in ~30% of tumor cells) and relapse (bottom, cMET intensity between 2+ and 3+ in 95% of tumor cells). Image represents 1.5% of the full scanned area, the full scans are provided in Supplementary Fig. 15. g Ex vivo response of FB295 to the combination of capmatinib and osimertinib. An on-target effect is observed across concentrations. P values in (d) and (g) from a two-sample two-sided Student’s t test comparing treatment condition to DMSO control, no adjustment for multiple testing. All box-plots as in Fig. 3e.