Personalized Treatment of Lung Adenocarcinoma

Abstract

Non–small cell lung cancer, most often known as adenocarcinoma, is notoriously fatal and less chemosensitive than many other solid and hematologic malignancies. Nonetheless, recent advances in the understanding of molecular cancer biology have allowed translational application of targeted agents in lung adenocarcinoma that work specifically on key proteins derived from common driver oncogenes. Notably, tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 receptor tyrosine kinase (ROS1) have received much clinical attention over the past few years. The treatment paradigm for advanced lung adenocarcinoma has subsequently changed markedly. Instead of treating all lung adenocarcinomas alike, it is now routine to determine the tumor’s genetic profile, specifically EGFR mutations, ALK rearrangement, and possibly ROS1 rearrangement, to achieve a customized treatment plan. There is now ample evidence to support the role of EGFR TKI as a first-line treatment of advanced EGFR-mutated lung adenocarcinoma, with an anticipated similar role for ALK TKI in ALK-rearranged tumor. A growing list of potentially targetable driver mutations in lung adenocarcinoma has also emerged, making personalized therapy in lung adenocarcinoma a possibility.