PANoptosis: A new era for anti-cancer strategies

Cancer cells possess an extraordinary ability to dodge cell death through various pathways, granting them a form of immortality-a key obstacle in oncotherapy. Thus, it's vital to unravel the intricate mechanisms behind newly discovered types of cell death that drive tumor suppression, going beyond apoptosis alone. The emergence of PANoptosis, a form of cell death intertwining necroptosis, pyroptosis, and apoptosis, offers a fresh perspective, integrating these pathways into one cohesive process. When cells detect damage signals, they assemble PANoptosome complexes that disrupt their balance, trigger immune responses, and lead to their eventual collapse. PANoptosis has been associated with multiple cellular pathways, including ferroptosis. Mitochondrial dysfunction also plays a critical role in sparking and advancing PANoptosis. In this review, we map out the molecular machinery and regulatory web controlling PANoptosis. We explore cutting-edge research and future trends in PANoptosis-centered tumor therapies, spotlighting promising innovations that could amplify cancer treatment effectiveness through harnessing this multifaceted cell death pathway. The development of nanomedicines and nanomaterials provides solutions to the therapeutic challenges of clinical drugs. Developing novel tumor nano-PANoptosis inducers by leveraging the advantages of nanomedicine is of research value. Traditional Chinese medicine (TCM) treatment is characterized by multiple targets, and it has distinct advantages in triggering PANoptosis through multiple pathways. Additionally, photodynamic Therapy (PDT) may offer new insights into promoting PANoptosis in tumor cells by increasing oxidative stress and reactive oxygen species levels. These will establish a solid theoretical groundwork for the development of integrated treatment methodologies.