Role of PANoptosis in cancer: molecular mechanisms and therapeutic insights

Dysregulated cell death signaling profoundly influences oncogenesis, making the targeted elimination of malignant cells a cornerstone of modern oncological interventions. Insights into programmed cell death kinetics have revealed cross-talk among apoptosis, pyroptosis, and necroptosis, establishing the conceptual framework of PANoptosis. As an inflammatory death modality, PANoptosis is orchestrated by a multi-subunit protein platform termed the PANoptosome, which integrates and executes these distinct death programs. This review outlines the fundamental molecular cascades governing PANoptosis, alongside its multifaceted involvement in tumorigenesis, immune microenvironment remodeling, and metastatic dissemination. Although PANoptosis potentiates host antitumor defense mechanisms, its impact on malignant progression remains context-dependent. Pharmacological intervention directed at central node molecules or combined with radiation and immune checkpoint blockade represents a compelling strategy. Notably, suppressing ZBP1 attenuates chemotherapy-induced systemic toxicities, whereas multimodal therapies synergistically augment therapeutic efficacy. Nevertheless, precise regulatory networks demand further elucidation, and clinical translation requires rigorous validation. Ultimately, PANoptosis offers novel insights into cancer biology and paves the way for personalized therapeutic paradigms.