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Molecular targeted therapies: Ready for “prime time” in biliary tract cancer
Journal of Hepatology ( IF 26.8 ) Pub Date : 2020-03-12 , DOI: 10.1016/j.jhep.2020.03.007
Angela Lamarca 1 , Jorge Barriuso 1 , Mairéad G McNamara 1 , Juan W Valle 1
Affiliation  

The prognosis for patients with biliary tract cancers (cholangiocarcinoma and gallbladder cancer) is poor, while the incidence of these cancers is increasing. Most patients are diagnosed with advanced disease when treatment options are limited to palliative approaches, mainly focused on chemotherapy. In recent years, novel treatment targets of relevance to biliary tract cancers, mainly present in patients with intrahepatic cholangiocarcinoma, have been identified and are rapidly changing the field. These include fibroblast growth factor receptor () fusions and isocitrate dehydrogenase ()-1 and -2 mutations which are each present in around 10–20% of patients with intrahepatic cholangiocarcinoma. In addition, inhibition of other pathways/molecules is currently being explored, including human epidermal growth factor receptor (HER) family members, the Wnt pathway, neurotropic tyrosine kinase receptor () fusions and mutations. The IDH1 inhibitor ivosidenib has already been tested in a phase III clinical trial in pretreated cholangiocarcinoma and showed benefit in terms of progression-free survival. Multiple FGFR inhibitors have consistently shown high response rates in phase II/III trials, especially for patients harbouring fusions. Herein, we provide an overview of the status of targeted therapies in biliary tract cancers, discussing the current clinical development of IDH and FGFR inhibitors in detail, as well as reviewing current caveats and future steps.

中文翻译:


分子靶向治疗:为胆道癌的“黄金时期”做好准备



胆道癌(胆管癌和胆囊癌)患者的预后较差,而这些癌症的发病率正在增加。当治疗选择仅限于姑息疗法(主要集中于化疗)时,大多数患者被诊断为晚期疾病。近年来,与胆道癌(主要存在于肝内胆管癌患者)相关的新治疗靶点已被确定,并正在迅速改变该领域。其中包括成纤维细胞生长因子受体 () 融合以及异柠檬酸脱氢酶 ()-1 和 -2 突变,这些突变分别存在于约 10-20% 的肝内胆管癌患者中。此外,目前正在探索其他途径/分子的抑制,包括人表皮生长因子受体(HER)家族成员、Wnt途径、亲神经酪氨酸激酶受体()融合和突变。 IDH1 抑制剂 ivosidenib 已经在经过预处理的胆管癌的 III 期临床试验中进行了测试,并显示出在无进展生存期方面的益处。多种 FGFR 抑制剂在 II/III 期试验中始终表现出高缓解率,特别是对于携带融合的患者。在此,我们概述了胆道癌靶向治疗的现状,详细讨论了 IDH 和 FGFR 抑制剂的当前临床开发,并回顾了当前的注意事项和未来的步骤。
更新日期:2020-03-12
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