pharmacoproteomics_crc

Most molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of >10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and transcriptomes of 145 cell lines and 89 patients defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype. Modelling the responses of 52 CRC cell lines to 577 drugs according to proteome profiles enabled predicting drug sensitivity for cell lines and patients. Among many novel associations, MERTK was identified as a predictive marker for resistance towards MEK1/2 inhibitors and immunohistochemistry of 1,000 CRC tumours confirmed MERTK as a prognostic survival marker. We provide the proteomic and pharmacological data as a resource to the community to e.g. facilitate the design of innovative prospective clinical trials.