TC‐induced ECs necroptosis has been proved to be the important pathogenesis of tumor hematogenous metastasis, thus the inhibition of the ECs necroptosis in the context of tumor progression represents a promising therapeutic target.[9, 44, 45, 46, 47, 48, 49] Recent findings about lung metastases of cancer cells in blood system provide a pioneering evidence that APP‐DR6 signaling pathway plays a critical role for ECs necroptosis and TCs extravasation, which indicates that inhibitors of DR6 are viewed as novel anti‐metastasis agents. The gene discussed is APP; the disease is neoplasm.