Methylation-dependent loss of RIPK3 expression is a common necroptosis resistance mechanism in cancer that seems to be driven by oncogenes and occurs progressively during tumor growth.19 33 Epigenetic regulation of MLKL is much less common, but a recent study in a pancancer multiomics analysis of necroptosis-related regulators associated hypermethylation of MLKL with poor overall survival in patients with malignant melanoma.34 The gene discussed is MLKL; the disease is melanoma.