Role of PANoptosis in cancer: Molecular mechanisms and therapeutic opportunities.

Abstract

PANoptosis is an inflammatory programmed cell death pathway. It integrates apoptosis, pyroptosis, and necroptosis via PANoptosome complexes, thereby coordinating immune responses and remodeling tumor microenvironment (TME). By overcoming limitations of therapies targeting a single-pathway (e.g., those targeting apoptosis), PANoptosis suppresses cancer progression, reverses drug resistance, and synergizes with radiotherapy through immune activation. Mechanistic insights are driving therapeutic strategies that target key regulators (ZBP1, RIPK3) and disease-specific miRNAs to modulate caspase-dependent and caspase-independent cascades. Its pathological duality-acute hyperactivation in tissue injury versus chronic dysregulation in degenerative diseases-highlights the need for context-dependent modulation. PANoptosis activation shows prognostic biomarker potential and universal therapeutic promise for drug-resistant cancers and inflammatory disorders, though clinical translation remains exploratory. This framework positions PANoptosis as a transformative paradigm bridging cell death dynamics and immune regulation.