Targeted therapies in advanced non-small cell lung cancer: success or failure?

Abstract

The progress in molecular oncology has resulted in developing numerous targeted anticancer agents, some of which have emerged as therapeutic options in non-small cell lung cancer (NSCLC). The largest clinical experience in this malignancy concerns inhibitors of epidermal growth factor receptor (EGFR), including small molecular tyrosine kinase inhibitors (erlotinib and gefitinib), and monoclonal antibody cetuximab. Of those, erlotinib and gefitinib are routinely used in first-line, second-line and maintenance therapy of advanced NSCLC. Another targeting agent approved in advanced NSCLC is a humanized anti-VEGF monoclonal antibody bevacizumab. Until so far, no valuable clinical efficacy has been documented for small-molecule VEGFR kinase inhibitors and anti-IGF-1R agents. Most recently, an impressive activity of crizotinib, an EML4-ALK inhibitor has been reported. Several other targeted agents are currently being tested in clinical trials. This article critically reviews the current achievements and failures in the targeted treatment of advanced NSCLC, with particular focus on the importance of molecular testing and treatment individualization.