{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:32:42Z","timestamp":1789086762804,"version":"build-2803163510"},"reference-count":4,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100021021","name":"Kobe City Medical Center General Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100021021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We present the case of a 34\u2010year\u2010old Japanese man with anaplastic lymphoma kinase (ALK)\u2010positive non\u2010small cell lung cancer and brain metastases. After central nervous system (CNS) disease progression with alecintib and brigatinib, treatment with lorlatinib resulted in a good intracranial response. In this case, we investigated brain penetration ratio of brigatinib using cerebrospinal fluid and paired serum samples, and the ratio was 0.012. Further, we investigated resistance mechanisms via next\u2010generation sequencing (NGS) using lung biopsy at lung cancer diagnosis and brain biopsy sample at progressive disease of brigatinib. No apparent resistance mechanism of known ALK resistance, such as <jats:italic>ALK<\/jats:italic> mutations, amplifications, epithelial\u2010mesenchymal transition (EMT) and bypass pathway activation were detected. Taken together, we speculate that the low CNS penetration rate of brigatinib confers CNS progression. Further studies are warranted to reveal the resistance mechanism and propose a treatment strategy for CNS progression in ALK\u2010positive patients.<\/jats:p>","DOI":"10.1111\/1759-7714.15395","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T06:09:46Z","timestamp":1719295786000},"page":"1772-1775","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Successful intracranial response of lorlatinib after resistance with alectinib and brigatinib in patients with <scp>ALK<\/scp>\u2010positive lung adenocarcinoma: Implications of <scp>CNS<\/scp> penetration rate of brigatinib"],"prefix":"10.1111","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7829-7524","authenticated-orcid":false,"given":"Yuki","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Kobe City Medical Center General Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiharu","family":"Sato","sequence":"additional","affiliation":[{"name":"DNA Chip Research Inc  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Irie","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics Faculty of Pharmaceutical Science, Kobe Gakuin University  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Nanjo","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kanazawa University Hospital  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Pathology Kobe City Medical Center General Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Neurology Kobe City Medical Center General Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Tomii","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kobe City Medical Center General Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9028309"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2056"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70362-6"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.02.015"}],"container-title":["Thoracic Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.15395","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T10:10:06Z","timestamp":1723543806000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1759-7714.15395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,24]]},"references-count":4,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/1759-7714.15395"],"URL":"https:\/\/doi.org\/10.1111\/1759-7714.15395","archive":["Portico"],"relation":{},"ISSN":["1759-7706","1759-7714"],"issn-type":[{"value":"1759-7706","type":"print"},{"value":"1759-7714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,24]]},"assertion":[{"value":"2024-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}