MLKL and cancer: In addition, Guan et al. [278] found that treatment of NecroIr1 and -2 complexes eradicated drug-resistant cancer cells by the induction of necroptosis events, including unregulated extracellular Ca2+ efflux, leakage of LDH and HMGB1, higher ROS generation, loss of ∆Ψm, and lastly, activation of RIPK3/MLKL-dependent necroptosis.