Shunta Mori, Hiroki Izumi, Mitsugu Araki, Jie Liu, Yu Tanaka, Yosuke Kagawa, Yukari Sagae, Biao Ma, Yuta Isaka, Yoko Sasakura, Shogo Kumagai, Yuta Sakae, Kosuke Tanaka, Yuji Shibata, Hibiki Udagawa, Shingo Matsumoto, Kiyotaka Yoh, Yasushi Okuno, Koichi Goto, Susumu S Kobayashi
The CLIP1-LTK fusion was recently discovered as a novel oncogenic driver in non-small cell lung cancer (NSCLC). Lorlatinib, a third-generation ALK inhibitor, exhibited a dramatic clinical response in a NSCLC patient harboring CLIP1-LTK fusion. However, it is expected that acquired resistance will inevitably develop, particularly by LTK mutations, as observed in NSCLC induced by oncogenic tyrosine kinases treated with corresponding tyrosine kinase inhibitors (TKIs). In this study, we evaluate eight LTK mutations corresponding to ALK mutations that lead to on-target resistance to lorlatinib...
April 4, 2024: Communications Biology