The evolving role of futibatinib for advanced cholangiocarcinoma.

IF 2.5 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Expert Review of Gastroenterology & Hepatology Pub Date : 2026-04-01 Epub Date: 2026-03-25 DOI:10.1080/17474124.2026.2649804

Mara Persano, Andrea Casadei-Gardini, Silvia Camera, Margherita Rimini

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引用次数: 0

Abstract

Introduction: Cholangiocarcinoma (CCA) continues to be classified as a rare cancer with high mortality rates, underscoring the urgent need for more effective systemic treatment strategies. The widespread implementation of next-generation sequencing has enabled comprehensive characterization of the genomic landscape of CCA, revealing a relatively high prevalence of actionable genetic alterations.

Areas covered: In this evolving therapeutic context, futibatinib has gained attention as a selective, irreversible pan-fibroblast growth factor receptor (FGFR) inhibitor that covalently binds to the FGFR kinase domain, thereby maintaining inhibitory activity against a broad spectrum of FGFR2 resistance mutations. This distinct mechanism of action represents a significant advancement over earlier reversible inhibitors and provides a strong biological rationale for its use in patients with FGFR2-altered CCA. A comprehensive literature search was performed in PubMed/MEDLINE, Embase, and Scopus for studies published from January 2000 to February 2026, using combinations of the terms 'cholangiocarcinoma,' 'FGFR2,' 'fibroblast growth factor receptor,' and 'futibatinib.' Relevant clinical trials, translational studies, and review articles were screened for inclusion.

Expert opinion: Futibatinib represents the most biologically rational FGFR inhibitor currently available for FGFR2-altered CCA, as it directly addresses the dominant mechanism limiting the efficacy of earlier agent, on-target resistance driven by secondary FGFR2 kinase domain mutations.

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福替替尼在晚期胆管癌中的作用。

导言：胆管癌（CCA）一直被归类为一种高死亡率的罕见癌症，强调迫切需要更有效的全身治疗策略。下一代测序的广泛应用使得CCA基因组景观的全面表征成为可能，揭示了可操作的遗传改变的相对较高的患病率。涵盖领域：在不断发展的治疗背景下，福替替尼作为一种选择性的、不可逆的泛成纤维细胞生长因子受体（FGFR）抑制剂引起了人们的关注，它与FGFR激酶结构域共价结合，从而保持对广谱FGFR2耐药突变的抑制活性。这种独特的作用机制代表了较早期可逆性抑制剂的重大进步，并为其用于fgfr2改变的CCA患者提供了强有力的生物学依据。我们在PubMed/MEDLINE、Embase和Scopus中对2000年1月至2026年2月发表的研究进行了全面的文献检索，使用术语“胆管癌”、“FGFR2”、“成纤维细胞生长因子受体”和“福替替尼”的组合。筛选相关临床试验、转化研究和综述文章纳入。专家意见：Futibatinib代表了目前可用于FGFR2改变的CCA的最具生物学合理性的FGFR抑制剂，因为它直接解决了限制早期药物疗效的主要机制，即由继发性FGFR2激酶结构域突变驱动的靶向耐药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Gastroenterology & Hepatology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

6.80

自引率

2.60%

发文量

审稿时长

6-12 weeks

期刊介绍： The enormous health and economic burden of gastrointestinal disease worldwide warrants a sharp focus on the etiology, epidemiology, prevention, diagnosis, treatment and development of new therapies. By the end of the last century we had seen enormous advances, both in technologies to visualize disease and in curative therapies in areas such as gastric ulcer, with the advent first of the H2-antagonists and then the proton pump inhibitors - clear examples of how advances in medicine can massively benefit the patient. Nevertheless, specialists face ongoing challenges from a wide array of diseases of diverse etiology.