Targeting ROS1 Rearrangements in Non-small Cell Lung Cancer: Crizotinib and Newer Generation Tyrosine Kinase Inhibitors

Abstract

ROS1 gene rearrangements exist in 1-2% of non-small cell lung cancers, typically occurring in younger, never or light smokers with adenocarcinoma. ROS1 gene fusions are potent oncogenic drivers, the presence of which results in the susceptibility of tumours to ROS1-targeted therapy. Crizotinib was the first tyrosine kinase inhibitor to demonstrate activity in ROS1-rearranged lung cancer, and remains the recommended first-line therapy for patients with advanced ROS1-rearranged non-small cell lung cancer. Despite excellent initial responses to crizotinib, the majority of patients develop disease progression, which may be intracranial or extracranial. Identification of resistance mechanisms to ..