Related Experiment Video
Updated: May 16, 2026
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Targeting late SV40 factor: is the achilles heel of hepatocarcinogenesis revealed?
1Institute of Gastroenterology and Liver Diseases, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel. amirsh@tasmc.health.gov.il
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.
Insights
Hepatocellular carcinoma (HCC) may be treatable by targeting a single oncogene, late SV-40 factor (LSF). A new molecule specifically inhibits LSF, causing significant cancer cell death in vitro and in vivo.
Area of Science:
- Oncology
- Molecular Biology
- Hepatology
Background:
- Hepatocellular carcinoma (HCC) is a significant cause of cancer mortality, often linked to chronic liver disease and cirrhosis.
- Current treatments like multi-kinase inhibitors target multiple pathways, but HCC's dependence on specific oncogenes is increasingly recognized.
- Late SV-40 factor (LSF) is an overexpressed transcription factor in HCC, correlating with tumor grade and aggressiveness.
Purpose of the Study:
- To investigate the potential of targeting a single oncogene, LSF, as a therapeutic strategy for HCC.
- To identify and evaluate molecules capable of inhibiting LSF activity in HCC cells.
Main Methods:
- Extensive drug screening was performed to identify inhibitors of LSF activity.
- The efficacy of a specific inhibitor, factor quinolinone inhibitor 1, was assessed in vitro and in vivo.
- LSF's role as an oncogene in HCC was examined, exploring the concept of "oncogene addiction".
Main Results:
- A novel molecule, factor quinolinone inhibitor 1, was identified that specifically blocks LSF's promoter-binding ability.
- Inhibition of LSF led to substantial HCC cell death in both laboratory and animal models.
- LSF was confirmed as a critical oncogene driving HCC proliferation and progression.
Conclusions:
- HCC exhibits "oncogene addiction" to LSF, presenting a potential therapeutic vulnerability.
- Targeting LSF with specific inhibitors like factor quinolinone inhibitor 1 offers a promising new avenue for HCC treatment.
- This single-molecule approach could represent a breakthrough in combating hepatocellular carcinoma.
Related Concept Videos
01:51Mechanisms of Retrovirus-induced Cancers
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...