Advances in mechanism and regulation of PANoptosis: Prospects in disease treatment

Abstract

PANoptosis, a new research hotspot at the moment, is a cell death pattern in which pyroptosis, apoptosis, and necroptosis all occur in the same cell population. In essence, PANoptosis is a highly coordinated and dynamically balanced programmed inflammatory cell death pathway that combines the main features of pyroptosis, apoptosis, and necroptosis. Many variables, such as infection, injury, or self-defect, may be involved in the occurrence of PANoptosis, with the assembly and activation of the PANoptosome being the most critical. PANoptosis has been linked to the development of multiple systemic diseases in the human body, including infectious diseases, cancer, neurodegenerative diseases, and inflammatory diseases. Therefore, it is necessary to clarify the process of occurrence, the regulatory mechanism of PANoptosis, and its relation to diseases. In this paper, we summarized the differences and relations between PANoptosis and the three types of programmed cell death, and emphatically expounded molecular mechanism and regulatory patterns of PANoptosis, with the expectation of facilitating the application of PANoptosis regulation in disease treatment.

Exploration of the prognostic prediction value of the PANoptosis‐based risk score and its correlation with tumor immunity in lung adenocarcinoma

“…25 Evidence demonstrated that several tumors such as colorectal cancer and prostatic cancer were possibly associated with PANoptosis. 12 Despite this, there are few studies reporting the relationships between PANoptosis and LUAD.…”

“…11 The assembly and activation of PANoptosome are deemed an organic response of selfprotection to prevent against virus, bacterial and fungal infections in infectious diseases. 12 Other than for infection, PANoptosis may also be associated with the occurrence and development of cancer. 13 Abnormal cell death is an imperative pathological mechanism of tumor progress, and increasing numbers of studies indicate that PANoptosis is involved in this progress.…”

“…PANoptosis is generally regulated by a cytoplasmic multimeric protein complex named PANoptosome 11 . The assembly and activation of PANoptosome are deemed an organic response of self‐protection to prevent against virus, bacterial and fungal infections in infectious diseases 12 . Other than for infection, PANoptosis may also be associated with the occurrence and development of cancer 13 .…”

PANoptosis in cancer, the triangle of cell death

“…Therefore, the regulation of PANoptosis is very important for the protection of the human system. In terms of the mechanism of PANoptosis, its regulation can be mainly divided into three parts: recognition of DAMPs and PAMPs, formation of PANoptosome, and activation of execution proteins 100 . However, due to the diversity of both pattern recognition receptors on the cell surface and death execution proteins, it is difficult to achieve the regulation of the whole PANoptosis process by focusing on a single molecule.…”

“…Despite the promising outlook of cancer therapies targeting PANoptosis, it is essential to note that treating cancer through PCD pathways and inflammatory signaling is a complex process closely tied to the specifics of the cancer type 100,146 . Therefore, selecting appropriate molecular targets for each specific cancer is critical, as different PCD pathways may perform different roles in various cancers.…”