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ID 115221
Taniguchi, Hirokazu Kanazawa University|Nagasaki University
Yamada, Tadaaki Kanazawa University|Kyoto Prefectural University of Medicine
Wang, Rong Kanazawa University
Tanimura, Keiko Kyoto Prefectural University of Medicine
Adachi, Yuta Kanazawa University
Nishiyama, Akihiro Kanazawa University
Tanimoto, Azusa Kanazawa University
Takeuchi, Shinji Kanazawa University
Araujo, Luiz H. Brazilian National Cancer Institute
Boroni, Mariana Brazilian National Cancer Institute
Yoshimura, Akihiro Kyoto Prefectural University of Medicine
Shiotsu, Shinsuke Japanese Red Cross Kyoto Daiichi Hospital
Matsumoto, Isao Kanazawa University
Watanabe, Satoshi Niigata University
Kikuchi, Toshiaki Niigata University
Miura, Satoru Niigata Cancer Center Hospital
Tanaka, Hiroshi Niigata Cancer Center Hospital
Kitazaki, Takeshi Japanese Red Cross Nagasaki Genbaku Hospital
Yamaguchi, Hiroyuki Nagasaki University
Mukae, Hiroshi Nagasaki University
Uchino, Junji Kyoto Prefectural University of Medicine
Takayama, Koichi Kyoto Prefectural University of Medicine
Yano, Seiji Kanazawa University
Content Type
Journal Article
A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells.
Journal Title
Nature Communications
Springer Nature
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