We developed a new pharmacoproteomics platform combining kinome activity profiling with a kinase inhibitor screen to identify pathway biomarkers of drug response in cancer cell lines.
Correlating 13935 kinome features to response for 299 kinase inhibitors, we scored individual features and 327 Reactome pathways for their relevance to drug action in 17 liver cancer cell lines. This is a great resource for deconvoluting target and mechanisms of action for kinase inhibitors. We developed a Shiny Web app for interactive visualization of this resource: https://quantbiology.org/hcckinome
Our data implicated the EMT in drug resistance and identified novel kinases important for distinct EMT states. Modulating these kinases sensitized resistant cells to drugs, validating our pharmacoproteomic platform to identify rational drug combinations.
With our kinome profiling approach, we can distinguish clinical HCC samples by etiology and identify pathway-based biomarkers in individual patient tumors. Important milestones in developing personalized treatments for HCC.