The treatment for anaplastic lymphoma kinase (ALK)-positive lung cancer has been rapidly evolving since the introduction of several ALK tyrosine kinase inhibitors (ALK-TKI) in clinical practice. However, the acquired resistance to these drugs has become an important issue. In this study, we collected a total of 112 serial biopsy samples from 32 patients with ALK-positive lung cancer during multiple ALK-TKI treatments to reveal the resistance mechanisms to ALK-TKI. Among 32 patients, 24 patients received more than two ALK-TKI. Secondary mutations were observed in 8 of 12 specimens after crizotinib failure (G1202R, G1269A, I1171T, L1196M, C1156Y and F1245V). After alectinib failure, G1202R and I1171N mutations were detected in 7 of 15 specimens. G1202R, F1174V and G1202R, and P-gp overexpression were observed in 3 of 7 samples after ceritinib treatment. L1196M + G1202R, a compound mutation, was detected in 1 specimen after lorlatinib treatment. ALK-TKI treatment duration was longer in th..... READ ARTICLE
Cancer Science DOI:10.1111/cas.14314
Authors: Noriko Yanagitani, Ken Uchibori, Sumie Koike, Mika Tsukahara, Satoru Kitazono, Takahiro Yoshizawa, Atsushi Horiike, Fumiyoshi Ohyanagi, Yuichi Tambo, Shingo Nishikawa, Naoya Fujita, Ryohei Katayama, Makoto Nishio