Klin Onkol 2006; 19(3): 171-176.
Summary
Lung cancer is the leading cause of cancer deaths worldwide. Standard therapy of non-small cell lung cancer (NSCLC) includes platinum-based chemotherapy in combination with other anticancer drugs. Novel effective agents recently introduced into clinics are small molecule tyrosine kinase inhibitors of the epidermal growth factor receptor (Egfr1). Egfr1 is frequently constitutively activated in majority of human cancers. Up-regulation of the Egfr1 signaling is associated with overexpression of egfr1, which may be due to amplification of egfr1 gene in the tumors cells. Likewise, somatic mutations in the kinase domain of egfr1 (exons 18-21) result in ligand-independent transduction, particularly in NSCLCs. Molecular analysis of Egfr1 status is useful indicator for prediction of tumor sensitivity or resistance to Egfr1 tailored therapy. The limitations of the targeted therapy are the intrinsic resistance (frequently due to k-ras mutations) and induction of drug resistance during therapy associated with secondary (epi)genetic alterations.
