Identification of somatic genomic alterations in circulating tumors cells: another step forward in non-small-cell lung cancer?

摘要

The last decade has witnessed substantial progress in defining the molecular determinants of non-small-cell lung cancer (NSCLC) and demonstrating how these can be exploited in the clinic. In 2004, the identification of somatic mutations in the epidermal growth factor receptor (EGFR) gene provided the first insight into a clinically relevant NSCLC driver oncogene.1"3 EGFR mutations in NSCLC are transforming, enhance the activity of the kinase domain of EGFR, and increase the affinity for EGFR tyrosine kinase inhibitors (TKIs).4 In EGPR-mutated NSCLCs (ie, tumors with classic EGFR exon 19 deletions or the L858R mutation, which are found in approximately 15% of all NSCLCs), clinical and radiographic responses are achieved in most patients with the use of two commercially available reversible EGFR TKIs: gefitinib and erlotinib.5 These EGFR TKIs improve outcomes when compared with cytotoxic chemotherapies,6"8 and the evidence-based use of these drugs, as recommended by the American Society of Clinical Oncology9 and other practice10 and regulatory agencies, is now restricted to EGFR-mutated NSCLCs in the first-line treatment of advanced tumors.