[Molecular diagnostics in lung carcinoma for therapy stratification]

Abstract

Lung cancer is the most common tumor-related cause of death in western industrialized countries, despite continuous improvement in both diagnostic and therapeutic approaches. Since epidermal growth factor receptor (EGFR) is overexpressed in 80% of cases of non-small cell lung carcinoma, mediating important carcinogenic properties such as cell-cycle progression, apoptosis, angiogenesis and metastasis, it is considered a relevant target in novel specific therapies. This has lead to the development of the low-molecular EGFR tyrosine kinase inhibitors (EGFR-TKI) Gefitinib and Erlotinib. Predicting which patients will respond to an EGFR-targeted therapy is of particular clinical interest. Recent studies show a significantly better response and prolonged progression-free survival in patients with EGFR-mutated tumors, even when used as first-line therapy. Moreover, genetic mutations which correlate to primary EGFR-TKI resistance (e.g. KRAS) or produce secondary resistance to known TKI (e.g. EGFR mutation T790 M or MET amplification) have meanwhile been explained. Predictive diagnosis of these mutations using histological material is becoming increasingly important for patient stratification and will soon be indispensable not only for lung cancer.