ROS-1 Fusions in Non-Small-Cell Lung Cancer: Evidence to Date

The ROS-1 gene plays a major role in the oncogenesis of numerous tumors. ROS-1 rearrangement is found in 0.9-2.6% of non-small-cell lung cancers (NSCLCs), mostly lung adenocarcinomas, with a significantly higher rate of women, non-smokers, and a tendency to a younger age. It has been demonstrated that ROS-1 is a true oncogenic driver, and tyrosine kinase inhibitors (TKIs) targeting ROS-1 can block tumor growth and provide clinical benefit for the patient. Since 2016, crizotinib has been the first-line reference therapy, with two-thirds of the patients' tumors responding and progression-free survival lasting similar to 20 months. More recently developed are ROS-1-targeting TKIs that are active against resistance mechanisms appearing under crizotinib and have better brain penetration. This review summarizes current knowledge on ROS-1 rearrangement in NSCLCs, including the mechanisms responsible for ROS-1 oncogenicity, epidemiology of ROS-1-positive tumors, methods for detecting rearrangement, phenotypic, histological, and molecular characteristics, and their therapeutic management. Much of this work is devoted to resistance mechanisms and the development of promising new molecules.

Automated summary

The ROS-1 gene is pivotal in the oncogenesis of various tumors, and targeting ROS-1 with tyrosine kinase inhibitors can effectively inhibit tumor growth. Crizotinib is the current first-line therapy with promising results, but newer ROS-1-targeting TKIs have been developed for improved efficacy.