Regulated cell death programs shaping cancer therapy

Regulated cell death has long been central to cancer therapy, with apoptosis historically regarded as the principal mechanism underlying treatment efficacy.

Increasing evidence now demonstrates that tumors engage a diverse array of regulated cell death programs, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, autophagy-associated death processes, and emerging stress-induced modalities such as parthanatos and disulfidptosis. These pathways can be broadly conceptualized as protein-governed, metabolism-driven, or stress-induced programs, reflecting distinct mechanistic principles and differing degrees of mechanistic definition and translational maturity. Their activation or suppression can influence tumor progression, immune modulation, and therapy resistance. While therapeutic induction of specific death modalities offers opportunities for tumor control, death-associated signaling may also paradoxically promote tumor adaptation and immune evasion under certain conditions.

This review integrates current understanding of regulated cell death programs to highlight their plasticity in cancer and underscores the importance of mechanism-guided targeting of death pathways to improve cancer therapy outcomes.

Not applicable.