To investigate the downstream pathways involved in EGFR upregulation that promote resistance to palbociclib in colorectal cancer, we conducted an analysis through proteomics. Firstly, we established a stable cell line with EGFR overexpression in the LOVO cell line using lentivirus. Subsequently, we cultured both the control and EGFR-overexpressing LOVO cells, and after confirming EGFR overexpression using Western blotting (WB), we collected the cells for proteomic sequencing.