Pyroptosis As a Novel Therapeutic Target in Glioblastoma Multiforme: Mechanisms, Molecular Insights, and Therapeutic Potential Publisher



Karimi S ; Dehpour A R ; Hadjighassem M ; Khajehnasiri A ; Yekta R A ; Aghaei M ; Majedi H ; Hosseindoost S
Source: Molecular Therapy Nucleic Acids Published:2026

Abstract

Glioblastoma multiforme (GBM) is the most malignant type of primary brain tumor. Its clinical management is challenging due to its heterogeneity, highly malignant nature, and insensitivity to standard treatments. While current strategies for GBM treatments are based on inducing apoptosis in GBM cells, some GBM tumors showed resistance to this type of cell death. Recent evidence indicates that pyroptosis is a novel, promising therapeutic method for overcoming tumor cells’ resistance to cancer treatment. This inflammatory programmed cell death type is mediated by the cleavage of gasdermin proteins. Based on the evidence, inducing pyroptosis is negatively associated with GBM growth and development; the exact molecular mechanisms and the signaling pathways underlying pyroptosis are not fully understood. This review presents the different pathways of pyroptosis and its role in GBM growth regulating and illustrates various drugs and components that modulate pyroptosis in GBM tumors. It also investigates the regulatory roles of noncoding RNAs in pyroptosis modulation in GBM tumors, providing promising therapeutic approaches that target pyroptosis as a novel strategy for GBM treatment. © 2026 The Author(s).