AIFM1 and esophageal squamous cell carcinoma: As illustrated in Fig. 6E, we propose a model to explain how YM155 induces PARP-mediated parthanatos cell death in ESCC cells: (i) the hyper-activation of PARP-1, leading to PAR and AIF translocation, (ii) the requirement of PARP-1 and AIF for YM155-induced necrosis, and (iii) the inhibition of mTOR pathways.