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World J Gastroenterol. Dec 14, 2012; 18(46): 6709-6711
Published online Dec 14, 2012. doi: 10.3748/wjg.v18.i46.6709
Targeting late SV40 factor: Is the achilles heel of hepatocarcinogenesis revealed?
Amir Shlomai
Amir Shlomai, Institute of Gastroenterology and Liver Diseases, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel
Author contributions: Shlomai A collected the material and wrote the manuscript
Correspondence to: Dr. Amir Shlomai, MD, PhD, Institute of Gastroenterology and Liver Diseases, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel. amirsh@tasmc.health.gov.il
Telephone: +972-3-6974282 Fax: +972-3-6974622
Received: May 7, 2012
Revised: May 29, 2012
Accepted: June 7, 2012
Published online: December 14, 2012
Abstract

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.

Keywords: Oncogene addiction; Hepatocellular carcinoma; Late SV40 factor; Transcription factor; Multi-kinase inhibit