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Metabolic cell death in cancer: mechanisms and therapeutic potential

Yujinpeng Hao1, Jun Shao1, Naqi Lian2

  • 1First Clinical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Apoptosis : an International Journal on Programmed Cell Death
|September 9, 2025
PubMed

Insights

Cancer cells resist cell death, but metabolic dysregulation triggers novel cell death pathways. This review explores metabolism-linked regulated cell death (RCD) and its therapeutic potential in oncology.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Research

Background:

  • Malignant tumors exhibit resistance to programmed cell death, enabling uncontrolled proliferation.
  • Metabolic dysregulation can induce a novel form of cell death, termed metabolism-linked regulated cell death (RCD).
  • RCD presents a new paradigm for cellular self-elimination in cancer.

Purpose of the Study:

  • To systematically review the molecular mechanisms of various metabolism-linked cell death modalities.
  • To critically evaluate the therapeutic potential of these RCD pathways in oncology.
  • To explore precision medicine strategies targeting metabolism-driven cell death in cancer.

Main Methods:

  • Systematic literature review.
  • Analysis of molecular mechanisms underlying RCD modalities.
  • Evaluation of therapeutic applications in cancer treatment.

Main Results:

  • Detailed analysis of pyroptosis, immunogenic cell death (ICD), necroptosis, ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, alkaliptosis, and methuosis.
  • Elucidation of the interplay among signaling cascades in metabolism-driven cell death.
  • Identification of RCD as a promising target for cancer therapy.

Conclusions:

  • Metabolism-linked RCD offers novel therapeutic avenues for cancer treatment.
  • Understanding these pathways is crucial for developing targeted precision medicine strategies.
  • Harnessing RCD can overcome cancer cell resistance to conventional therapies.
Keywords:
CancerMetabolic cell deathMolecular mechanismTherapeutic drugs

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