European Molecular Biology Laboratory, Heidelberg, Germany.
Institute of Pathology, University Hospital Heidelberg, Germany.
J Hepatol. 2017 Nov;67(5):1051-1061. doi: 10.1016/j.jhep.2017.06.021. Epub 2017 Jul 1.
Hepatocellular carcinoma (HCC) is among the most prevalent human malignancies worldwide with rising incidence in industrialised countries, few therapeutic options and poor prognosis. To expand and improve therapeutic strategies, identification of drug targets involved in several liver cancer-related pathways is crucial. Virtually all signal transduction cascades cross the nuclear envelope and therefore require components of the nuclear transport system (NTS), including nuclear transport receptors (e.g. importins and exportins) and the nuclear pore complex. Accordingly, members of the NTS represent promising targets for therapeutic intervention. Selective inhibitors of nuclear export have already entered clinical trials for various malignancies. Herein, we review the current knowledge regarding alterations of the NTS and their potential for targeted therapy in HCC.
肝细胞癌 (HCC) 是全球最常见的人类恶性肿瘤之一,在工业化国家发病率不断上升,治疗选择有限,预后较差。为了扩大和改进治疗策略,确定涉及几种肝癌相关途径的药物靶点至关重要。实际上,所有信号转导级联都穿过核膜,因此需要核转运系统 (NTS) 的组件,包括核转运受体 (例如进口蛋白和出口蛋白) 和核孔复合体。因此,NTS 的成员是治疗干预的有前途的靶点。核输出的选择性抑制剂已进入各种恶性肿瘤的临床试验。本文综述了 NTS 的改变及其在 HCC 靶向治疗中的潜在应用的最新知识。