Advances in Treatment of Lung Cancer With Targeted Therapy

Context.-Ongoing preclinical investigations and clinical trials involving new targeted therapies promise to improve survival for patients with lung cancer. Targeted therapeutic agents, based on genetic mutations and signaling pathways altered in lung cancer, have added significantly to our armamentarium for lung cancer treatment while minimizing drug toxicity. To date, 4 targeted therapies have been approved for treatment of lung cancer by the US Food and Drug Administration: gefitinib in 2002, erlotinib in 2003, bevacizumab in 2006, and crizotinib in 2011. Objective.-To review targeted therapies in lung cancer, the molecular biomarkers that identify patients likely to benefit from these targeted therapies, the basic molecular biology principles, selected molecular diagnostic techniques, and pathologic features correlated with molecular abnormalities in lung cancer. To review new molecular abnormalities described in lung cancer that are predictive for response to novel promising targeted agents in various phases of clinical trials. Data Sources.-Review of the literature covering the molecular abnormalities of lung cancer with a focus on the molecular diagnostics and targeted therapy. Special emphasis is placed on summarizing evolving technologies useful in the diagnosis and characterization of lung cancer. Conclusions.-Molecular testing of lung cancer expands the expertise of the pathologist, who will identify the tumor markers that are predictive of sensitivity or resistance to various targeted therapies and allow patients with cancer to be selected for highly effective and less toxic therapies. (Arch Pathol Lab Med. 2012;136:504-509; doi: 10.5858/arpa.2011-0618-RA)