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Regulated cell death programs shaping cancer therapy
1Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
Background:
Regulated cell death has long been central to cancer therapy, with apoptosis historically regarded as the principal mechanism underlying treatment efficacy.
Main Body:
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.
Conclusions:
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.
Clinical Trial Registration:
Not applicable.
Insights
Cancer therapy traditionally focused on apoptosis, but tumors utilize diverse regulated cell death pathways. Understanding these diverse death programs is key to improving cancer treatment outcomes.
Area of Science:
- Oncology
- Cell Biology
- Molecular Medicine
Background:
- Regulated cell death is crucial in cancer therapy, with apoptosis historically considered the primary mechanism.
- Tumors employ a wide spectrum of regulated cell death programs beyond apoptosis.
Purpose of the Study:
- To review the diverse regulated cell death programs in cancer.
- To highlight the plasticity of these pathways and their role in cancer progression and therapy resistance.
- To emphasize mechanism-guided targeting of death pathways for improved cancer therapy.
Main Methods:
- Literature review integrating current understanding of regulated cell death programs.
- Categorization of pathways into protein-governed, metabolism-driven, or stress-induced.
- Analysis of the influence of these pathways on tumor progression, immune modulation, and therapy resistance.
Main Results:
- Tumors utilize diverse regulated cell death pathways including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and others.
- These pathways exhibit distinct mechanistic principles and varying translational maturity.
- Activation or suppression of these death programs impacts tumor progression, immune response, and resistance to therapy.
Conclusions:
- Regulated cell death programs display significant plasticity in cancer.
- Targeting specific death pathways offers therapeutic opportunities but may also promote tumor adaptation.
- A mechanism-guided approach to targeting cell death pathways is essential for enhancing cancer therapy outcomes.
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