Biomarkers to Predict Response to Epidermal Growth Factor Receptor Inhibitors

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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 non-small 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 a cohort that includes 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 form 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 phosphoryla...

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