Cholangiocarcinoma (CCA) remains a devastating malignancy and a significant challenge to treat. The majority of CCA patients are diagnosed at an advanced stage, making the disease incurable in most cases. The advent of high-throughput genetic sequencing has significantly improved our understanding of the molecular biology underpinning cancer. The identification of ‘druggable’ genetic aberrations and the development of novel targeted therapies against them is opening up new treatment strategies. Currently, 3 targeted therapies are approved for use in CCA; Ivosidenib in patients with IDH1 mutations and Infigratinib/Pemigatinib in those with FGFR2 fusions. As our understanding of the biology underpinning CCA continues to improve it is highly likely that additional targeted therapies will become available in the near future. This is important, as it is thought up to 40 % of CCA patients harbour a potentially actionable mutation. In this review we provide an overview of the molecular pathogenesis of CCA and highlight currently available and potential future targeted treatments.

中文翻译：

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胆管癌的分子生物学及其对患者管理中靶向治疗的影响

胆管癌（CCA）仍然是一种毁灭性的恶性肿瘤，也是治疗的重大挑战。大多数 CCA 患者在诊断时已处于晚期，使得这种疾病在大多数情况下无法治愈。高通量基因测序的出现极大地提高了我们对癌症分子生物学的理解。 “可药用”基因畸变的识别以及针对它们的新型靶向疗法的开发正在开辟新的治疗策略。目前，有3种靶向疗法被批准用于CCA； Ivosidenib 用于 IDH1 突变患者，Infigratinib/Pemigatinib 用于 FGFR2 融合患者。随着我们对 CCA 生物学基础的了解不断提高，在不久的将来很可能会出现更多的靶向治疗。这很重要，因为据认为高达 40% 的 CCA 患者携带潜在的可操作突变。在这篇综述中，我们概述了 CCA 的分子发病机制，并重点介绍了当前可用的和未来潜在的靶向治疗。