Epidermal Growth Factor Receptor Targeting in Glioblastoma Therapy

Glioblastoma remains the most aggressive primary brain tumour, characterised by rapid proliferation, diffuse invasion and dismal prognosis. Aberrant activation of the epidermal growth factor receptor (EGFR), through gene amplification, overexpression or oncogenic mutations such as EGFRvIII, underlies key malignant features by driving the MAPK and PI3K/Akt signalling cascades. Therapeutic strategies have focused on small‐molecule tyrosine kinase inhibitors, monoclonal antibodies and antibody–drug conjugates directed against EGFR or its variants, as well as vaccine and RNA-based approaches. Clinical outcomes have been hampered by intratumoral heterogeneity, adaptive resistance through compensatory pathway activation, and the challenge of delivering agents across the blood–brain barrier. Recent advances aim to overcome these barriers through next-generation inhibitors with improved central nervous system penetration, combination regimens to block parallel signalling routes and network-level targeting inspired by insights into epigenetic and kinase interplay. A more personalised approach, guided by tumour molecular profiling and innovative delivery systems, is emerging as the roadmap for meaningful improvements in patient survival and quality of life.

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Epidermal Growth Factor Receptor Targeting in Glioblastoma Therapy publication trend

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Technical terms

EGFR: A receptor tyrosine kinase that regulates cell proliferation and survival, frequently amplified or mutated in glioblastoma.

EGFRvIII: A constitutively active mutant form of EGFR lacking a portion of the extracellular domain, driving persistent oncogenic signalling in a subset of tumours.

Tyrosine kinase inhibitor: A small‐molecule drug that binds to the ATP‐site of a kinase to block its enzymatic activity and downstream signalling.

PI3K/Akt pathway: A downstream signalling cascade activated by receptor tyrosine kinases that promotes cell growth, survival and metabolism.

Blood–brain barrier: A selective physiological barrier that restricts the passage of most therapeutic agents from the bloodstream into the central nervous system.

References

1. Current and future therapeutic strategies for high-grade gliomas leveraging the interplay between epigenetic regulators and kinase signaling networks. Journal of Experimental & Clinical Cancer Research (2024).
2. Dual blockade of EGFR and PI3K signaling pathways offers a therapeutic strategy for glioblastoma. Cell Communication and Signaling (2023).
3. The third-generation EGFR inhibitor AZD9291 overcomes primary resistance by continuously blocking ERK signaling in glioblastoma. Journal of Experimental & Clinical Cancer Research (2019).