The research focuses on the longitudinal analysis of phosphoproteomic profiles in patients with recurrent colorectal liver metastases. Twenty-four individuals who underwent initial and recurrent resections for colorectal liver metastases participated in the study. Tissue samples were systematically collected throughout the treatment period from the liver metastases and normal liver tissue of each of the 24 patients at two timepoints. To validate the therapeutic candidate, we conducted a phosphoproteomics analysis of cell lines treated with AZD6482 and xenograft samples treated with copanlisib. The analysis aimed to assess the pharmacological effects of these treatments.