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PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation

Mohit Bhardwaj1, Kirti Upmanyu2, Saurabh Upadhyay3,4

  • 1Kusuma School of Biological Sciences Indian Institute of Technology Delhi, Delhi, India.

Genes and Immunity
|March 3, 2026
PubMed

Insights

PANoptosis, a unified inflammatory cell death program, integrates apoptosis, pyroptosis, and necroptosis. Targeting PANoptosis offers new therapeutic strategies for diseases ranging from cancer to neurodegeneration.

Area of Science:

  • Cell Biology
  • Immunology
  • Pharmacology

Background:

  • Programmed cell death pathways (apoptosis, pyroptosis, necroptosis) were considered distinct.
  • Emerging evidence shows convergence into PANoptosis, a unified inflammatory cell death program.
  • PANoptosis is orchestrated by supramolecular PANoptosome complexes.

Purpose of the Study:

  • Synthesize recent advances in PANoptosis molecular architecture.
  • Highlight cross-regulatory redundancies, novel modulators, and post-translational checkpoints.
  • Provide a framework for pharmacological intervention and therapeutic opportunities.

Main Methods:

  • Review of molecular architecture of PANoptosis.
  • Integration of upstream sensors, scaffolding adaptors, and executioners.
  • Analysis of pharmacological interventions and clinical trials.

Main Results:

  • PANoptosis integrates multiple cell death pathways via PANoptosome complexes.
  • Dysregulated PANoptosis contributes to various diseases including cancer, sepsis, and neurodegeneration.
  • A Clinical Polarity and Timing Model guides therapeutic induction versus restraint.

Conclusions:

  • PANoptosis presents novel therapeutic targets and an adjuvant framework.
  • Selective modulation of PANoptosis could transform management of infectious, inflammatory, oncologic, and neurodegenerative diseases.
  • Emerging biomarkers aid patient stratification and monitoring.

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