Lung Cancer Genotype-Based Therapy and Predictive Biomarkers Present and Future

Context.-The advent of genotype-based therapy and predictive biomarkers for lung cancer has thrust the pathologist into the front lines of precision medicine for this deadly disease. Objective.-To provide the clinical background, current status, and future perspectives of molecular targeted therapy for lung cancer patients, including the pivotal participation of the pathologist. Data Sources.-Data were obtained from review of the pertinent peer-reviewed literature. Conclusions.-First-generation tyrosine kinase inhibitors have produced clinical response in a limited number of non-small cell lung cancers demonstrated to have activating mutations of epidermal growth factor receptor or anaplastic lymphoma kinase rearrangements with fusion partners. Patients treated with first-generation tyrosine kinase inhibitors develop acquired resistance to their therapy. Ongoing investigations of second-generation tyrosine kinase inhibitors and new druggable targets as well as the development of next-generation genotyping and new antibodies for immunohistochemistry promise to significantly expand the pathologist's already crucial role in precision medicine of lung cancer. (Arch Pathol Lab Med. 2012; 136: 1482-1491; doi: 10.5858/arpa.2012-0508-RA)