{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:32:18Z","timestamp":1782739938496,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015642","name":"Japan Lung Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015642","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3\u2010mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against <jats:italic>ALK<\/jats:italic>\u2010rearranged non\u2010small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several <jats:italic>ALK<\/jats:italic>\u2010rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several <jats:italic>ALK<\/jats:italic>\u2010rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal\u2013epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib\u2010treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of <jats:italic>ALK<\/jats:italic>\u2010rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin\u201015 (IL\u201015) mRNA levels were elevated in gilteritinib\u2010treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL\u201015 production along with NK cell infiltration may constitute components of the gilteritinib\u2010mediated antitumor responses in <jats:italic>ALK<\/jats:italic>\u2010rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against <jats:italic>ALK<\/jats:italic>\u2010rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.<\/jats:p>","DOI":"10.1111\/cas.15958","type":"journal-article","created":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T03:49:22Z","timestamp":1694836162000},"page":"4343-4354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Efficacy of gilteritinib in comparison with alectinib for the treatment of <i>ALK<\/i>\u2010rearranged non\u2010small cell lung cancer"],"prefix":"10.1111","volume":"114","author":[{"given":"Chihiro","family":"Ando","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology and Respiratory Medicine Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical 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