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However, for unresectable BTCs, systemic therapy has been uniformly applied. Gemcitabine and cisplatin (GC) therapy and GC-based therapies were established as the first-line standard BTC treatment. However, no highly effective second-line therapy has been established, and the prognosis remains poor, highlighting the need for further therapeutic advancements. Meanwhile, the era of precision medicine has expanded the use of genetic testing, leading to the identification of actionable molecular targets in BTC. Several targeted therapies, including FGFR inhibitors and IDH1 inhibitors, have been developed, offering new second-line treatment options and the potential for first-line use in appropriate cases. Notably, the frequency of these genetic alterations varies depending on the tumor location, demonstrating the molecular heterogeneity of BTC. Therefore, it has been recognized that a tailored treatment approach for each BTC patient may be more effective than uniform systemic therapy. Consequently, although routine genetic testing before initiating systemic treatment is currently limited by the medical environment (e.g., cost, accessibility, regional differences), it is recommended in ESMO guideline and might be increasingly advocated. However, BTC harbors a wide range of genetic alterations, and numerous targeted therapies are being developed accordingly. This review provides an overview of the reported genetic alterations in BTC, the frequencies of these alterations, and the corresponding targeted therapies, emphasizing the evolving role of precision medicine in BTC treatment.<\/jats:p>","DOI":"10.1007\/s10147-025-02761-x","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T17:35:35Z","timestamp":1745602535000},"page":"1069-1079","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genomic landscape of biliary tract cancer and corresponding targeted treatment strategies"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6702-3800","authenticated-orcid":false,"given":"Daisaku","family":"Yamada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Doki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Eguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"2761_CR1","unstructured":"Surgery JSoH-B-P (2021) General rules for Clinical and pathological studies on cancer of the biliary tract: the 7th edition. 7th edn., Tokyo"},{"key":"2761_CR2","unstructured":"Network NCC (2024) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae) Biliary Tract Cancers Version 6.2024 www.nccn.org\/patients. 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