Clinically, CSI is applied as an adjuvant cancer therapy not a single compound, with our findings demonstrating that CSI-derived bufadienolides notably suppress pancreatic cancer cell proliferation by inducing G2/M arrest, potentially via the p-EGFR/KRAS/p-ERK1/2 pathway (Figure 5). Here, MAPK3 is linked to familial pancreatic carcinoma.