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Updated: Aug 15, 2026
Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
Biomarkers to predict response to epidermal growth factor receptor inhibitors
Daphne A Haas-Kogan1, Michael D Prados, Kathleen R Lamborn
1Department of Radiation Oncology, University of California-San Francisco, USA. hkogan@radonc.17.ucsf.edu
Abstract:
Epidermal growth factor receptors (EGFRs) are amplified and overexpressed in many different human cancers, a phenomenon generally associated with poor prognosis. Inhibitors of the tyrosine kinase activity associated with this receptor have been approved for the treatment of chemotherapy-refractory nonsmall cell lung cancer, and are in clinical trials for additional tumor types. While these inhibitors, gefitinib and erlotinib, display limited response rates when assessed in cohorts that include all patients, there are subgroups, defined by patient and tumor characteristics, that preferentially respond to these agents. We recently performed an analysis of tumors obtained from a Phase I trial of erlotinib in patients with glioblastoma multiforme (GBM), the most common malignant brain tumor in adults. We showed that patients whose tumors exhibited overexpression and amplification of EGFR responded better than patients who had normal levels of this gene and protein. We also demonstrated that the phosphorylation state of PKB/Akt was an important determinant for response, with low phospho-PKB/Akt levels predicting good response to erlotinib. We discuss these findings in the context of recent molecular analyses of the placebo-controlled Phase III trials that led to approval of EGFR inhibitors. These data underscore the importance of placebo-controlled trials to distinguish between prognostic indicators of disease progression more generally and predictive markers of response to therapy. Ultimately the goal of these studies is to allow selection of patients who will preferentially respond to EGFR inhibitors.
Insights
Epidermal growth factor receptor (EGFR) inhibitors show promise for certain cancers. Tumors with high EGFR levels and low phospho-PKB/Akt responded best to erlotinib in glioblastoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Epidermal growth factor receptors (EGFRs) are frequently amplified and overexpressed in human cancers, correlating with poor prognosis.
- Tyrosine kinase inhibitors targeting EGFR, such as gefitinib and erlotinib, are approved for non-small cell lung cancer and are under investigation for other tumor types.
- Response rates to EGFR inhibitors vary, suggesting patient and tumor subgroups may preferentially benefit from these treatments.
Purpose of the Study:
- To investigate the predictive markers of response to erlotinib in patients with glioblastoma multiforme (GBM).
- To analyze the relationship between EGFR amplification/overexpression and PKB/Akt phosphorylation status with erlotinib efficacy.
- To differentiate prognostic indicators from predictive markers for EGFR inhibitor therapy.
Main Methods:
- Analysis of tumor samples from a Phase I trial of erlotinib in GBM patients.
- Assessment of EGFR amplification and overexpression levels.
- Evaluation of the phosphorylation state of PKB/Akt.
Main Results:
- Patients with EGFR-overexpressing and amplified tumors showed a better response to erlotinib.
- Low levels of phospho-PKB/Akt predicted a favorable response to erlotinib.
- Findings align with molecular analyses from placebo-controlled Phase III trials of EGFR inhibitors.
Conclusions:
- EGFR amplification/overexpression and PKB/Akt phosphorylation status are potential predictive markers for erlotinib response in GBM.
- Placebo-controlled trials are crucial for distinguishing prognostic factors from predictive therapeutic markers.
- Identifying patient subgroups who will preferentially respond to EGFR inhibitors is key for optimizing cancer treatment.
