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Targeting EGFR in glioblastoma: lessons from a disappointing journey. A systematic review
Ali Berro1, Ahmad Assi2, Sarah Samhat2
1Department of Neurosurgery, Hotel-Dieu de France, Beirut, Lebanon - ali.berro2@net.usj.edu.lb.
Background:
This review aims to review the efficacy and toxicity of anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in the management of glioblastoma.
Methods:
A systematic review was completed utilizing PubMed, Cochrane, and Embase databases up to February 2025. Boolean operators and the MeSH term "glioma" were used, along with relevant keywords related to EGFR.
Results:
First- and second-generation EGFR-focused TKIs performed poorly in patients with GBM. The use of erlotinib in combination with radiotherapy, alkylating agents, and anti-angiogenic agents yielded the best outcomes in patients with newly diagnosed GBM.
Conclusions:
EGFR-focused TKIs were largely disappointing as a treatment for GBM. Longstanding issues, including treatment resistance, tumor heterogeneity, and blood-brain barrier penetration persist. Future efforts must focus on tackling these issues, and prioritizing patient selection via biomarkers.
Insights
Anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) showed limited efficacy for glioblastoma (GBM) management. Combination therapies, particularly erlotinib with other agents, offered better outcomes, but challenges like resistance and blood-brain barrier penetration remain.
Area of Science:
- Neuro-oncology
- Molecular targeted therapy
- Cancer drug development
Background:
- Glioblastoma (GBM) remains a challenging brain tumor with limited treatment options.
- Anti-epidermal growth factor receptor (EGFR) therapies have been explored for GBM management.
- Understanding the efficacy and toxicity of these agents is crucial.
Conclusions:
- Significant challenges persist, including treatment resistance, tumor heterogeneity, and blood-brain barrier penetration.
- Future research should address these limitations.
- Biomarker-driven patient selection is essential for optimizing EGFR-TKI therapy in GBM.
