Current state of precision therapy for the management of lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is a subtype of non small-cell lung cancer that has been characterized by late stage diagnosis and poor clinical outcomes. Recent advances in tumor genotyping and precision therapies have shifted the landscape of LUAD management, drastically improving outcomes for a large subset of patients. Specific tyrosine kinase inhibitors have been developed to target oncogenic aberrations harbored by different molecular subtypes of LUAD. Although many of these targeted therapies have proven to be more efficacious than traditional chemotherapy, the constant battle against acquired resistance has limited their success. This has warranted the development of second- and third-generation tyrosine kinase inhibitors, chronically directed at more and more specific targets. This review focuses on the eight most frequent LUAD oncogenic drivers and the effectiveness of their associated targeted therapies. The goal of this thesis is to evaluate each molecular target as a candidate for precision medicine, identify targeted therapies which hold the most promise, and characterize the current state of LUAD precision therapy. By comparing progression free survival rates, safety profiles, and resistance data for each genetic aberration, it was concluded that epidermal growth factor receptor (EGFR) and ROS proto-oncogene 1 (ROS1) directed therapies hold the most promise for improving clinical outcomes for EGFR mutant-positive and ROS1 fusion-positive patient populations. Though curative options will likely not be seen in the near future, the progress made by precision medicine is encouraging. By focusing further research on elucidating resistance mechanisms, identifying novel oncogenic drivers, and trialing combination therapies, patient outcomes can continue to improve.