Background: Central nervous system (CNS) metastasis, such as brain metastasis and leptomeningeal carcinomatosis (LMC), occurs in 20–40% of all patients with cancer. Anaplastic lymphoma kinase (ALK) is a clinically validated drug target and ALK rearrangements are found in approximately 3-5% of non-small cell lung cancer (NSCLC). ALK tyrosine kinase inhibitor (TKI) shows dramatic clinical efficacy in ALK-rearranged NSCLC patients, and the second-generation ALK-TKI alectinib is effective against CNS metastasis of ALK-rearranged NSCLC. However, the patients with ALK-rearrangement acquire resistance to alectinib over time and develop recurrent LMC metastasis. This study aimed to clarify the mechanism of resistance to alectinib in LMC and seek a novel therapeutic strategy. Conclusion: We demonstrated that EML4-ALK lung cancer cells acquired moderate resistance to alectinib in the leptomeningeal space due to amphiregulin-triggered EGFR activation. Moreover, combined use of alectinib and EGFR..... READ ARTICLE
Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1841
Authors: S. Arai, S. Takeuchi, K. Fukuda, A. Nishiyama, A. Tanimoto, H. Taniguchi, M. Satouchi, S. Nanjo, R. Katayama, M. Nishio, M. Zheng, Y. Wu, S. Yano
