Targeting late SV40 factor: Is the achilles heel of hepatocarcinogenesis revealed?

作     者：Amir Shlomai 

作者机构：Institute of Gastroenterology and Liver Diseases Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine Tel-Aviv University 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2012年第18卷第46期

页      面：6709-6711页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：肝癌细胞 SV40 后期 转录因子 单个分子 原癌基因 导向药物 酶抑制剂 

摘      要：Hepatocellular carcinoma (HCC) is a dreadful cancer and a major cause of death among patients with chronic liver disease and cirrhosis. The apparent alterations in a diversity of intracellular pathways found in HCC has set the rational for developing molecular-directed drugs that simultaneously inhibit multiple pathways, such as the multi-kinase inhibitor Sorafenib. However, recently this concept has been challenged by showing that HCC is heavily dependent on a single oncogene designated late SV-40 factor (LSF), a transcription factor that is over-expressed in liver cancer cells and that its expression is strongly correlated with tumor grade and aggressiveness. Furthermore, using an intensive screening for drugs that inhibit LSF activity, Grant et al have found a molecule designated factor quinolinone inhibitor 1 that can specifically block the ability of LSF to bind its target promoters, resulting in a massive death of HCC cells both in vitro and in vivo. The innovative findings of HCC representing oncogene addiction to LSF and the ability of a single molecule to block the activity of this oncogene resulting in tumor abolishment are encouraging and provide us with the hope that the Achilles heel of HCC has been found.