Biomarkers in Lung Adenocarcinoma A Decade of Progress

Context.-The analysis of molecular biomarkers in lung adenocarcinoma (ACA) is now a central component of pathologic diagnosis and oncologic care. The identification of an EGFR mutation or ALK rearrangement in advanced-stage lung ACA will dictate a change in first-line treatment from standard chemotherapy to targeted inhibition of these oncogenic alterations. Viable approaches to therapeutic targeting of KRAS-mutated ACA are now under investigation, raising the possibility that this too will become an important predictive marker in this tumor type. The recognized array of less common oncogenic alterations in lung ACA, including in the ROS1, RET, BRAF, and ERBB2 genes, is growing rapidly. The therapeutic implications of these findings are, in many cases, still under investigation. Objective.-To focus on the major molecular biomarkers in lung ACA, recommended testing strategies, the implications for targeted therapies, and the mechanisms that drive development of resistance. Data Sources.-Our current understanding of predictive and prognostic markers in lung ACA is derived from a decade of technical advances, clinical trials, and epidemiologic studies. Many of the newest discoveries have emerged from application of high-throughput next-generation sequencing and gene expression analyses in clinically and pathologically defined cohorts of human lung tumors. Conclusions.-Best practices require a solid understanding of relevant biomarkers for diagnosis and treatment of patients with lung ACA.