Experimental Hepatology and Drug Targeting (HEVEFARM), University of Salamanca, IBSAL, Salamanca, Spain; Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.
Experimental Hepatology and Drug Targeting (HEVEFARM), University of Salamanca, IBSAL, Salamanca, Spain; Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.
Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt B):1444-1453. doi: 10.1016/j.bbadis.2017.06.005. Epub 2017 Jul 7.
One of the main difficulties in the management of patients with advanced cholangiocarcinoma (CCA) is their poor response to available chemotherapy. This is the result of powerful mechanisms of chemoresistance (MOC) of quite diverse nature that usually act synergistically. The problem is often worsened by altered MOC gene expression in response to pharmacological treatment. Since CCA includes a heterogeneous group of cancers their genetic signature coding for MOC genes is also diverse; however, several shared traits have been defined. Some of these characteristics are shared with other types of liver cancer, namely hepatocellular carcinoma and hepatoblastoma. An important goal in modern oncologic pharmacology is to develop novel strategies to overcome CCA chemoresistance either by increasing drug specificity, such as in targeted therapies aimed to inhibit receptors with tyrosine kinase activity, or to increase the amounts of active agents inside CCA cells by enhancing drug uptake or reducing efflux through export pumps. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
胆管癌（CCA）患者管理的主要困难之一是他们对现有化疗的反应不佳。这是由于具有相当不同性质的强大化疗耐药机制（MOC）协同作用的结果。通常，药物治疗会导致 MOC 基因表达改变，从而使问题恶化。由于 CCA 包括一组异质性癌症，因此其编码 MOC 基因的遗传特征也多种多样；然而，已经确定了一些共同的特征。其中一些特征与其他类型的肝癌（即肝细胞癌和肝母细胞瘤）共享。在现代肿瘤药理学中，一个重要的目标是开发新的策略来克服 CCA 的化疗耐药性，方法是提高药物特异性，例如针对具有酪氨酸激酶活性的受体的靶向治疗，或者通过增强药物摄取或减少通过外排泵的流出来增加 CCA 细胞内的有效药物含量。本文是由 Jesus Banales、Marco Marzioni、Nicholas LaRusso 和 Peter Jansen 编辑的特刊“健康和疾病中的胆管细胞”的一部分。
