Taken together, our observations suggest that inhibition of EGFR signalling in a background of epirubicin treatment selectively induces the downregulation of the G1/S negative regulator p21 and the upregulation of the S phase-promoting cyclin E1 in EGFR-amplified gastric cancer PDOs, thereby leading to increased flux to the S phase of the cell cycle. This evidence concerns the gene CDKN1A and gastric cancer.