Sequential Fibroblast Growth Factor Receptor Inhibition in Intrahepatic Cholangiocarcinoma: Navigating an Evolving Landscape of Resistance and Opportunity-A Case Report and Current Opinion.

IF 3.2 Q2 ONCOLOGY

Oncology and Therapy Pub Date : 2025-08-16 DOI:10.1007/s40487-025-00371-1

Hideki Sasanuma, Hironori Yamaguchi

{"title":"Sequential Fibroblast Growth Factor Receptor Inhibition in Intrahepatic Cholangiocarcinoma: Navigating an Evolving Landscape of Resistance and Opportunity-A Case Report and Current Opinion.","authors":"Hideki Sasanuma, Hironori Yamaguchi","doi":"10.1007/s40487-025-00371-1","DOIUrl":null,"url":null,"abstract":"<p><p>Fibroblast growth factor receptor (FGFR)2 rearrangements define a distinct molecular subset of intrahepatic cholangiocarcinoma (iCCA) with therapeutic potential using FGFR inhibitors. However, acquired resistance invariably limits long-term efficacy, posing a significant clinical challenge. Sequential targeting with different FGFR inhibitors is an emerging strategy, yet robust evidence, particularly for third-line and beyond, is scarce, and a consensus on optimal sequencing and patient selection remains unreached. Here, we report a case of FGFR2-rearranged iCCA where the patient achieved a radiographic partial response (PR) to tasurgratinib (a third-line FGFR inhibitor) following prior progression on pemigatinib and futibatinib. This case underscores the sustained dependency on the FGFR pathway and highlights the potential clinical utility of rationally sequenced FGFR-targeted therapy even after multiple lines of treatment. More broadly, this report serves as a basis for a current opinion on the evolving landscape of sequential FGFR inhibition in iCCA. We delve into the complexities of acquired resistance, dissect the arguments for and against prolonged FGFR pathway blockade, explore the impact of co-occurring genomic alterations, discuss the controversies, research priorities, and the urgent need for a balanced perspective to guide future clinical practice and trial design in this rapidly advancing but still uncertain field.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncology and Therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40487-025-00371-1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Fibroblast growth factor receptor (FGFR)2 rearrangements define a distinct molecular subset of intrahepatic cholangiocarcinoma (iCCA) with therapeutic potential using FGFR inhibitors. However, acquired resistance invariably limits long-term efficacy, posing a significant clinical challenge. Sequential targeting with different FGFR inhibitors is an emerging strategy, yet robust evidence, particularly for third-line and beyond, is scarce, and a consensus on optimal sequencing and patient selection remains unreached. Here, we report a case of FGFR2-rearranged iCCA where the patient achieved a radiographic partial response (PR) to tasurgratinib (a third-line FGFR inhibitor) following prior progression on pemigatinib and futibatinib. This case underscores the sustained dependency on the FGFR pathway and highlights the potential clinical utility of rationally sequenced FGFR-targeted therapy even after multiple lines of treatment. More broadly, this report serves as a basis for a current opinion on the evolving landscape of sequential FGFR inhibition in iCCA. We delve into the complexities of acquired resistance, dissect the arguments for and against prolonged FGFR pathway blockade, explore the impact of co-occurring genomic alterations, discuss the controversies, research priorities, and the urgent need for a balanced perspective to guide future clinical practice and trial design in this rapidly advancing but still uncertain field.

查看原文本刊更多论文

序贯成纤维细胞生长因子受体抑制在肝内胆管癌中：导航一个不断变化的耐药性和机会-一个病例报告和当前观点。

成纤维细胞生长因子受体（FGFR）2重排定义了肝内胆管癌（iCCA）的一个独特分子亚群，使用FGFR抑制剂具有治疗潜力。然而，获得性耐药总是限制了长期疗效，构成了重大的临床挑战。不同FGFR抑制剂的顺序靶向治疗是一种新兴策略，但缺乏强有力的证据，特别是三线及以上的证据，并且关于最佳测序和患者选择的共识仍未达成。在这里，我们报告了一例fgfr2重排的iCCA，患者在先前使用pemigatinib和futibatinib取得进展后，对tasurgratinib（一种三线FGFR抑制剂）获得放射学部分缓解（PR）。该病例强调了对FGFR通路的持续依赖，并强调了合理排序的FGFR靶向治疗的潜在临床应用，即使在多种治疗方法之后。更广泛地说，该报告可作为当前关于iCCA中FGFR序次抑制发展前景的观点的基础。我们深入研究了获得性耐药的复杂性，剖析了支持和反对延长FGFR通路阻断的争论，探讨了共同发生的基因组改变的影响，讨论了争议，研究重点，以及在这个快速发展但仍不确定的领域中，迫切需要一个平衡的视角来指导未来的临床实践和试验设计。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Oncology and Therapy ONCOLOGY-

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

6 weeks

期刊介绍： Now indexed in PubMed Aims and Scope Oncology and Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Oncology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of clinical therapies. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts. Digital features and plain language summaries Oncology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Please see here for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550 Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case by case basis and should be sent to the journal editor. Copyright Oncology and Therapy''s content is published open access under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0 Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of £3650/€4500/$5100. The journal will consider fee discounts for developing countries and this is decided on a case by case basis. Open Access All articles published by Oncology and Therapy are published open access Contact For more information about the journal, including pre-submission enquiries, please contact managing editor Lydia Alborn at lydia.alborn@springer.com.