Updated project metadata. Previous high throughput gene expression profiling combined with a HCT116 colon cancer tumor spheroid-based drug-screening assay identified context-dependent treatment responses to OXPHOS inhibitors resulting in a shunting towards the mevalonate pathway. To complement these findings with a characterization of the proteome we use mass-spectrometry based proteomics to investigate protein profiles and context-dependent treatment responses in PMCTS and QMCTS compared to monolayer cells.