The NLRP3 signaling pathway is a potential target for clinical translation in glioma treatment.

Abstract

Glioma, particularly glioblastoma (GBM), stands as the most prevalent and formidable tumor in neurosurgery, marked by relatively poor prognosis and high recurrence rates. Despite significant advancements in multimodal therapies-encompassing surgical intervention, radiotherapy, and systemic treatments such as chemotherapy and targeted agents-the overall survival rate for GBM still remains around 5%. In high-grade gliomas, dysregulated inflammatory pathways critically undermine the efficacy of surgical resection and subsequent targeted chemoradiotherapy, which are pivotal for managing these aggressive malignancies. Even with refined surgical techniques and chemotherapeutic mainstays like temozolomide (TMZ), patient prognoses persist in bleak territory, as survival rates languish far below clinical expectations. The NLRP3 inflammatory signaling pathway, extensively studied in this context, drives pathogenesis through allosteric activation and assembly into the NLRP3 inflammasome, catalyzing the maturation of IL-1β and IL-18, thereby triggering cascading inflammatory responses and pyroptosis. The NLRP3 signaling pathway plays a pivotal role in tumor progression and inflammatory responses, and targeted drugs have already entered Phase I clinical trials. Clinically, NLRP3 can serve as a prognostic biomarker, while the combined application of NLRP3-targeted drugs with novel materials and their technical specifics require further exploration. This review explores the NLRP3 pathway's mechanistic role in glioma progression, reviews cutting-edge clinical research on NLRP3-targeting therapeutics, and evaluates the transformative potential of modulating this pathway in glioma treatment-offering referential insights into its clinical implications and the inflammatory microenvironment's interplay with tumor dynamics.