Clusterin:Review of research progress and looking ahead to direction in hepatocellular carcinoma  

作　　者：Peng Xiu Xiao-Feng Dong Xin-Ping Li Jie Li 

机构地区：[1]Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University [2]Department of Hepatobiliary Surgery, The People’s Hospital of Guangxi Zhuang Autonomous Region

出　　处：《World Journal of Gastroenterology》2015年第27期8262-8270,共9页世界胃肠病学杂志（英文版）

基　　金：Supported by National Nature Science Foundation of China,No.81172331 and No.30972890;Shandong Provincial Medicine and Health Science Technology Development Planning,China,No.2013WS0145

摘　　要：Liver cancer, a large proportion of which is hepatocellular carcinoma(HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen(OGX-011) is a novel 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase Ⅲ clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.Liver cancer, a large proportion of which is hepatocellular carcinoma(HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen(OGX-011) is a novel 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase Ⅲ clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.

关 键 词：HEPATOCELLULAR carcinoma CLUSTERIN Custirsen Chemotherapy ANTISENSE OLIGONUCLEOTIDES 

分 类 号：R735.7[医药卫生—肿瘤]