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The Emerging Role of Senolytics as a Next-Generation Strategy Against Glioma Recurrence: A Narrative Review
Andrea Filardo1, Isabella Coscarella1, Jessica Bria1
1Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy.
Cancers
|May 4, 2026
Summary
Cellular senescence, a double-edged sword in cancer, promotes glioblastoma recurrence after therapy. Senolytic drugs like Navitoclax, Quercetin, and Fisetin offer a promising strategy to eliminate senescent cells and improve patient outcomes.
Area of Science:
- Oncology
- Cellular Biology
- Neuro-oncology
Background:
- Cellular senescence is a paradox in cancer, halting tumors but promoting recurrence.
- Standard glioblastoma (GBM) therapies induce therapy-induced senescence (TIS), creating a pro-tumor microenvironment.
- Senescent cells release factors (SASP) that fuel immunosuppression, invasiveness, and drug resistance.
Purpose of the Study:
- To review the role of cellular senescence in GBM.
- To analyze senolytic drugs as a therapeutic strategy against GBM.
- To explore molecular mechanisms of senolytic agents and potential combination therapies.
Main Methods:
- Review of literature on cellular senescence, GBM, and senolytic agents.
- Analysis of molecular targets including Bcl-2 family and PI3K/AKT/mTOR pathway.
- Examination of synthetic (Navitoclax) and natural (Quercetin, Fisetin) senolytic compounds.
Main Results:
- Senescent cells, induced by GBM therapies, promote tumor recurrence via SASP.
- Senolytic drugs target anti-apoptotic pathways and the PI3K/AKT/mTOR axis.
- Navitoclax, Quercetin, and Fisetin demonstrate potential in eliminating senescent cells.
Conclusions:
- Senolytic adjuvants integrated into standard GBM protocols could eliminate residual disease.
- Combining senolytics with neuroprotective agents may improve GBM patient prognosis.
- Targeting therapy-induced senescence offers a novel therapeutic frontier for glioblastoma.
