Role of PANoptosis in cancer: molecular mechanisms and therapeutic insights

Abnormal cell death plays a crucial role in cancer development. Inducing tumor cell death is an important strategy for cancer treatment. Against this backdrop, with the in-depth study of the regulatory mechanisms of cell death, the discovery of interactions existing among pyroptosis, apoptosis, and necroptosis has resulted in the emergence of the concept of PANoptosis. This review article summarizes the discovery and molecular mechanisms of PANoptosis, as well as its roles in cancer development, tumor microenvironment regulation, and tumor metastasis, and explores its application prospects in cancer treatment. PANoptosis can promote anti-tumor immunity, but it has a dual-edged role in tumor metastasis. Targeted therapies against its key signaling molecules and combination therapies have shown promising results. For example, inhibiting the activity of ZBP1 can reduce the side effects of chemotherapy, and the combination of multiple molecules with radiotherapy or immunotherapy can enhance the therapeutic effect. However, in-depth research is still needed on the interaction and regulation mechanisms of its signaling pathways, as well as the activation mechanisms and functions of some molecules. Moreover, relevant targeted therapies and combination therapy regimens require more clinical trials for verification. In summary, PANoptosis provides a new perspective for tumor research and is expected to promote the development of precision medicine for tumors.