Studies have revealed that various cell death programs play alternating roles and exhibit extensive crosstalk, which results in resistance to one pathway sensitizing cells to death via another pathway in a specific environment.27,28 We thereby blocked one component of PANoptosis to explore the effect on other components and found that the silencing of caspase-3, caspase-7, or TFRC in CRC cells robustly increased the phosphorylation of MLKL, which may be caused by the heterogeneity among cells (Supplementary Fig. S2g–j). The gene discussed is CASP3; the disease is colorectal carcinoma.