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Pyroptosis as a novel therapeutic target in glioblastoma multiforme: Mechanisms, molecular insights, and therapeutic
Shokooh Karimi1, Ahmad Reza Dehpour2,3, Mahmoudreza Hadjighassem1,4
1Pain Research Center, Neuroscience Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
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.
Insights
Pyroptosis, an inflammatory cell death, shows promise for treating glioblastoma multiforme (GBM) brain tumors resistant to apoptosis. Targeting pyroptosis pathways offers a novel therapeutic strategy for GBM treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis.
- GBM exhibits heterogeneity and resistance to conventional apoptosis-inducing therapies.
- Pyroptosis, a programmed inflammatory cell death, presents a potential alternative therapeutic avenue.
Purpose of the Study:
- To review the molecular mechanisms and signaling pathways of pyroptosis in GBM.
- To explore drugs and compounds that modulate pyroptosis in GBM.
- To investigate the role of noncoding RNAs in pyroptosis for GBM treatment.
Main Methods:
- Literature review of pyroptosis pathways and their role in GBM.
- Analysis of therapeutic agents targeting pyroptosis in GBM.
- Examination of noncoding RNA regulation of pyroptosis in GBM.
Main Results:
- Pyroptosis induction is negatively correlated with GBM growth and development.
- Various drugs and components can modulate pyroptosis in GBM.
- Noncoding RNAs play a regulatory role in pyroptosis modulation within GBM tumors.
Conclusions:
- Pyroptosis is a promising therapeutic strategy for overcoming GBM resistance to apoptosis.
- Targeting pyroptosis pathways, including noncoding RNA regulation, offers novel treatment approaches for GBM.
