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胆道癌的靶向治疗——当前的局限性与未来的潜力

Targeted therapy in biliary tract cancers-current limitations and potentials in the future.

作者信息

Sahu Selley, Sun Weijing

机构信息

Division of Oncology, Department of Medicine Hematology, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15232, USA.

出版信息

J Gastrointest Oncol. 2017 Apr;8(2):324-336. doi: 10.21037/jgo.2016.09.16.

Abstract

Biliary tract cancers (BTC)/Cholangiocarcinoma (CCA) is an aggressive biliary tract epithelial malignancy from varying locations within the biliary tree with cholangiocyte depreciation., including intrahepatic cholangiocarcinoma (iCCA) (iCCA), extrahepatic cholangiocarcinoma (eCCA) and gallbladder carcinoma (GBC). The disease is largely heterogeneous in etiology, epidemiology, and molecular profile. There are limited treatment options and low survival rates for those patients with advanced or metastatic disease. Systemic treatment is confined to cytotoxic chemotherapy with the combination of gemcitabine and cisplatin. Lack of a stereotype genetic signature makes difficult in identification of potential actionable target directly, which may also explain lack of obvious clinic benefit with target oriented agents from current studies. It is crucial to understand of BTC carcinogenesis, tumor-stroma interactions, and key molecular pathways, and herald to establish targeted, individualized therapies for the heterogeneous disease, and eventually to improve the survival and overall outcome of patients.

摘要

胆道癌(BTC)/胆管癌(CCA)是一种侵袭性的胆道上皮恶性肿瘤,起源于胆管树内不同位置,伴有胆管细胞退变,包括肝内胆管癌(iCCA)、肝外胆管癌(eCCA)和胆囊癌(GBC)。该疾病在病因、流行病学和分子特征方面存在很大异质性。对于晚期或转移性疾病患者,治疗选择有限且生存率较低。全身治疗仅限于吉西他滨和顺铂联合的细胞毒性化疗。缺乏固定的基因特征使得直接识别潜在的可操作靶点变得困难,这也可能解释了目前研究中靶向药物缺乏明显临床获益的原因。了解BTC的致癌机制、肿瘤-基质相互作用和关键分子途径,对于为这种异质性疾病建立靶向、个体化治疗方法,并最终改善患者的生存率和总体预后至关重要。

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