Cholangiocarcinoma is a disease entity comprising diverse epithelial tumours with features of cholangiocyte differentiation: cholangiocarcinomas are categorized according to anatomical location as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Each subtype has a distinct epidemiology, biology, prognosis, and strategy for clinical management. The incidence of cholangiocarcinoma, particularly iCCA, has increased globally over the past few decades. Surgical resection remains the mainstay of potentially curative treatment for all three disease subtypes, whereas liver transplantation after neoadjuvant chemoradiation is restricted to a subset of patients with early stage pCCA. For patients with advanced-stage or unresectable disease, locoregional and systemic chemotherapeutics are the primary treatment options. Improvements in external-beam radiation therapy have facilitated the treatment of cholangiocarcinoma. Moreover, advances in comprehensive whole-exome and transcriptome sequencing have defined the genetic landscape of each cholangiocarcinoma subtype. Accordingly, promising molecular targets for precision medicine have been identified, and are being evaluated in clinical trials, including those exploring immunotherapy. Biomarker-driven trials, in which patients are stratified according to anatomical cholangiocarcinoma subtype and genetic aberrations, will be essential in the development of targeted therapies. Targeting the rich tumour stroma of cholangiocarcinoma in conjunction with targeted therapies might also be useful. Herein, we review the evolving developments in the epidemiology, pathogenesis, and management of cholangiocarcinoma.

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胆管癌—不断发展的概念和治疗策略

胆管癌是一种疾病实体，包括具有胆管细胞分化特征的多种上皮肿瘤：胆管癌根据解剖位置分为肝内（iCCA），肝门周围（pCCA）或远端（dCCA）。每个亚型都有独特的流行病学，生物学，预后和临床管理策略。在过去的几十年中，全球胆管癌的发病率特别是iCCA有所增加。手术切除仍是所有这三种疾病亚型潜在治愈的主要手段，而新辅助化学放疗后的肝移植仅限于部分pCCA早期患者。对于晚期或无法切除的疾病，局部和全身化疗是主要的治疗选择。外束放射疗法的改进促进了胆管癌的治疗。此外，全面的全外显子组和转录组测序的进展已经定义了每种胆管癌亚型的遗传格局。因此，已经确定了精密医学的有希望的分子靶标，并且正在临床试验中进行评估，包括那些探索免疫疗法的靶标。生物标志物驱动的试验，其中根据解剖胆管癌亚型和遗传畸变对患者进行分层，对于开发靶向疗法至关重要。结合靶向疗法靶向胆管癌的丰富肿瘤基质也可能是有用的。在本文中，我们回顾了胆管癌的流行病学，发病机理和治疗方法的发展。