Apart from the above-mentioned artificial loss of RIPK3 expression under in vitro culture conditions, epigenetic silencing by hypermethylation of promoter regions of critical necroptosis machinery components, particularly RIPK3, has been identified as a common escape mechanism in different cancer types in vivo.19 20 Hypomethylating agents such as 5-AD or 5-AZA have been used in experimental settings to circumvent epigenetic silencing of RIPK3 and MLKL. Here, MLKL is linked to cancer.