Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer.

ABSTRACT: Precision oncology approaches for patients with colorectal cancer (CRC) continue to lag behind other solid cancers. Functional precision oncology-a strategy that is based on perturbing primary tumor cells from cancer patients-could provide a road forward to personalize treatment. We extend this paradigm to measuring proteome activity landscapes by acquiring quantitative phosphoproteomic data from patient-derived organoids (PDOs). We show that kinase inhibitors induce inhibitor- and patient-specific off-target effects and pathway crosstalk. Reconstruction of the kinase networks revealed that the signaling rewiring is modestly affected by mutations. We show non-genetic heterogeneity of the PDOs and upregulation of stemness and differentiation genes by kinase inhibitors. Using imaging mass-cy

SUBMITTER: Plattner C 

PROVIDER: S-EPMC10692669 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature