Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal hepatobiliary neoplasm whose incidence is increasing. Largely neglected for decades as a rare malignancy and frequently misdiagnosed as carcinoma of unknown primary, considerable clinical and investigative attention has recently been focused on iCCA worldwide. The established standard of care includes first-line (gemcitabine and cisplatin), second-line (FOLFOX) and adjuvant (capecitabine) systemic chemotherapy. Compared to hepatocellular carcinoma, iCCA is genetically distinct with several targetable genetic aberrations identified to date. Indeed, FGFR2 and NTRK fusions, and IDH1 and BRAF targetable mutations have been comprehensively characterised and clinical data is emerging on targeting these oncogenic drivers pharmacologically. Also, the role of immunotherapy has been examined and is an area of intense investigation. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research.

中文翻译：

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肝内胆管癌的全身治疗

肝内胆管癌（iCCA）是一种高致死率的肝胆肿瘤，其发病率正在增加。几十年来，作为一种罕见的恶性肿瘤，在很大程度上被忽视，并经常被误诊为不明原发癌，最近在全球范围内对 iCCA 引起了相当大的临床和调查关注。既定的护理标准包括一线（吉西他滨和顺铂）、二线（FOLFOX）和辅助（卡培他滨）全身化疗。与肝细胞癌相比，iCCA 在遗传上是不同的，迄今为止已发现几种可靶向的遗传畸变。事实上，FGFR2 和 NTRK 融合以及 IDH1 和 BRAF 可靶向突变已经得到全面表征，并且正在出现关于在药理学上靶向这些致癌驱动因素的临床数据。还，免疫疗法的作用已经过研究，并且是一个深入研究的领域。在此，我们将及时、专题地回顾这些进展并突出未来的研究方向。