A novel ROS1 G2032 K missense mutation mediates lorlatinib resistance in a patient with ROS1-rearranged lung adenocarcinoma but responds to nab-paclitaxel plus pembrolizumab

Rearrangements in ROS1 oncogene, reported in 1 –2% of patients with non-small cell lung cancer (NSCLC), define a separate molecular sub-group of NSCLC [1]. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor with the ability to cross the blood-brain barrier and have sub-nanomolar enzymatic efficacy in ta rgeting rearrangements in ALK and ROS1 [2]. ROS1 G2032R has been reported as the most commonly acquired mutation that mediates resistance to crizotinib therapy [3–5]; however, mechanisms that mediate lorlatinib resistance among patients with ROS1 rearrangement are rarely reported.

Source: Lung Cancer - March 18, 2020 Category: Cancer & Oncology Authors: Yuling Zhou, Wenjuan Jiang, Liang Zeng, Jinye Mi, Lianxi Song, Analyn Lizaso, Xinru Mao, Nong Yang, Yongchang Zhang Source Type: research