ABSTRACT

Introduction: Cholangiocarcinoma (CCA) is an aggressive cancer type with a dismal prognosis. CCA typically presents at an advanced stage when surgical resection is not feasible, and systemic chemotherapy is generally of limited benefit. Thus, developing effective therapies against this deadly tumor is imperative and remains an unmet need. The advent of high-throughput approaches has led to a better delineation of each CCA subtype’s molecular landscape and the identification of promising candidates for targeted therapies. In this scenario, the recent approval of pemigatinib, a pan-Fibroblast Growth Factor Receptor (FGFR) inhibitor, for the treatment of the CCA subtype characterized by FGFR2 mutations, represents the first of numerous novel therapies against this disease.

Areas covered

This review provides an overview regarding the current scenario and knowledge of the CCA genomic landscape and the potentially actionable molecular aberrations in each CCA subtype.

Expert opinion

The establishment and advances of high-throughput methodologies applied to genetic and epigenetic profiling are changing many cancer types' therapeutic landscape , including CCA.The large body of data generated must be interpreted appropriately and eventually implemented in clinical practice. The following advancements toward precision medicine in CCA management will require designing better clinical trials with improved methods to stratify biliary tumor patients.

中文翻译：

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当前支撑胆管癌遗传基础的挑战

摘要

简介：胆管癌（CCA）是一种侵袭性癌症，预后不佳。CCA 通常出现在晚期，此时手术切除不可行，全身化疗通常效果有限。因此，开发针对这种致命肿瘤的有效疗法势在必行，而且仍然是一个未得到满足的需求。高通量方法的出现使得我们能够更好地描绘每种 CCA 亚型的分子图谱，并鉴定出有希望的靶向治疗候选药物。在这种情况下，最近批准的泛成纤维细胞生长因子受体（FGFR）抑制剂pemigatinib用于治疗以FGFR2突变为特征的CCA亚型，这是针对该疾病的众多新疗法中的第一个。

覆盖领域

本综述概述了 CCA 基因组景观的当前情况和知识，以及每个 CCA 亚型中潜在可操作的分子畸变。

专家意见

用于遗传和表观遗传分析的高通量方法的建立和进步正在改变许多癌症类型的治疗前景，包括 CCA。产生的大量数据必须得到适当的解释并最终在临床实践中实施。CCA 管理中精准医学的后续进展将需要设计更好的临床试验，并采用改进的方法对胆道肿瘤患者进行分层。