{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T05:35:46Z","timestamp":1792992946227,"version":"4.5.0"},"reference-count":29,"publisher":"The Korean Association for the Study of the Liver","issue":"2","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00261820"],"award-info":[{"award-number":["RS-2023-00261820"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-202400348654"],"award-info":[{"award-number":["RS-202400348654"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2023R1A2C2004339"],"award-info":[{"award-number":["2023R1A2C2004339"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["RS-2024-00407544"],"award-info":[{"award-number":["RS-2024-00407544"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["C-2023-0040"],"award-info":[{"award-number":["C-2023-0040"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["6-2022-0106"],"award-info":[{"award-number":["6-2022-0106"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-cmh.org"],"crossmark-restriction":true},"short-container-title":["Clin Mol Hepatol"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:p>Background\/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC.Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy.Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591\u20130.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in &lt;i&gt;TP53&lt;\/i&gt; (35.2%), &lt;i&gt;KRAS&lt;\/i&gt; (16.4%), &lt;i&gt;SMAD4&lt;\/i&gt; (10.5%), and &lt;i&gt;TNFRSF14&lt;\/i&gt; (10.5%), involving RTK\/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478\u20133.124) and OS (HR 2.096; 95% CI 1.413\u20133.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (P&lt;sub&gt;interaction&lt;\/sub&gt;=0.023 for PFS, P&lt;sub&gt;interaction&lt;\/sub&gt;=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC.Conclusions: Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.<\/jats:p>","DOI":"10.3350\/cmh.2025.1019","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:45:57Z","timestamp":1766969157000},"page":"721-736","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular determinants of outcome to gemcitabine, cisplatin, and nab-paclitaxel in patients with advanced biliary tract cancer"],"prefix":"10.3350","volume":"32","author":[{"given":"Daeseong","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam 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