Highlights d Systematic identification of colon cancer-associated proteins and phosphosites d Proteomics-supported neoantigens and cancer/testis antigens in 78% of the tumors d Rb phosphorylation is an oncogenic driver and a putative target in colon cancer d Glycolysis inhibition may render MSI tumors more sensitive to checkpoint blockade

Highlights d Comparison of ovarian cancer and normal precursors identifies key signaling pathways d Mitotic and cyclin-dependent kinases emerge as potential therapeutic targets d Previously identified hallmarks of homologous repair status and survival are confirmed d Replication stress appears to drive increased chromosomal instability

Highlights d Stepwise model of early to late gilteritinib resistance recapitulates human disease d Early resistant cells in marrow microenvironment rely on AURKB to resume growth d Pre-existing NRAS mutations expand in late resistance and drive relapse d Metabolic reprogramming occurs during evolution of gilteritinib resistance

jointly supervised the work (joint senior authorship).

The relationships of kinase levels and activity have been investigated using large, high quality proteomic and phosphoproteomic data sets from tumors. Results show that the protein levels of some kinases correlate with their activity and that activation of kinases is a complex process. This study provides the first analysis of kinase activity in cancer integrating proteomic and phosphoproteomic data.