Acquired <i>MET D1228N</i> Mutations Mediate Crizotinib Resistance in Lung Adenocarcinoma with <i>ROS1</i> Fusion: A Case Report
Yu Wang, Zheng Chen, Xiao Han, Jiamei Li, Honglin Guo, Junping Shi
Abstract
Patients with non-small cell lung cancer (NSCLC) containing ROS1 fusions can have a marked response to the ROS1-targeted tyrosine kinase inhibitors (TKIs), such as crizotinib. Common resistance mechanisms of ROS1-fusion targeted therapy are acquired mutations in ROS1. Along with the use of next-generation sequencing in the clinical management of patients with NSCLC during sequential targeted therapy, many mechanisms of acquired resistance have been discovered in patients with activated tyrosine kinase receptors. Besides acquired resistance mutations, bypass mechanisms of resistance to epidermal growth factor receptor (EGFR)-TKI treatment are common in patients with EGFR mutations. Here we describe a patient with metastatic lung adenocarcinoma with CD74-ROS1 fusion who initially responded to crizotinib and then developed resistance by the acquired mutation of D1228N in the MET kinase domain, which showed short-term disease control for cabozantinib. KEY POINTS: The D1228N point mutation of MET is an acquired mutation for crizotinib resistance. The patient obtained short-term clinical benefit from cabozantinib therapy after resistance to crizotinib. The clinical use of next-generation sequencing could maximize the benefits of precision medicine in patients with cancer.