Liver Cancer Gene Identified at VCU
Scientists at Virginia Commonwealth University have identified a gene that appears to be key in the development of liver cancer the third leading cause of cancer deaths in the world.
Researchers at the Massey Cancer Center found a tumor-promoting gene, called LSF, that is active in 90% of liver patients:
Sarker: The importance of osteopontin is very well known in the field of tumor biology, but the fact that LSF can regulate osteopontin and by this way it can promote tumor genesis is a completely new finding.
Dr. Devanand Sarker is the principal investigator in the research.
Sarker: And since LSF is the regulator of osteopontin, if you can block LSF then we can actually significantly impede the liver cancer progression and maybe we can even prevent the development.
The VCU team is collaborating with a scientist at Boston University.
Sarker: Her name is Dr. Ulla Hansen and her lab has developed some drug that can actually bind to LSF and prevent its function.
The work, Dr. Sarker said, is providing fresh insights into the complex etiology and mechanism of carcinogenesis process.
Sarker: So we are now collaborating with her to test if this drug can be used to either inhibit the disease or if we can prevent this disease.
The identification of LSF was the result of the sequential process of an ongoing study of AG-1, a gene with similar progression patterns.
Sarker: We cloned the AG-1 gene and have been studying this gene for quite a long time. And we were looking for the mediator genes that mediate the function of AG-1. And AG-1 actually also promotes tumor and we were looking a downstream mediator of AG-1. While looking for that we identified LSF. And a lot of the functions of AG-1 are actually similar to the functions of LSF and we believe that AG-1, by turning on LSF, can promote liver cancer development and progression. And in this way we can block LSF, that would actually give us some benefit from both AG-1 mediated action as well as actions from LSFic cells.
The team, he explained, is now testing LSF clinically.
Sarker: One team will have identified that when we look at the biopsy samples of liver cancer patients that LSF expression gradually increases as the disease becomes more aggressive. erefore, LSF expression can be used as a prognostic marker in biopsy samples. Secondly, we have identified previously that LSF not only helps in tumor progression,but it also contributes to resistance to other human therapeutic drugs. So one of the major problems of liver cances is that it is very resistant to currently used chemotherapeutics.
If current studies, using animals, produce results, the next step is to convince the Food and Drug Administration.
Sarker: Another thing is that the physicians can actually correlate whether this drug would be effective in patients, because in the biopsy samples they would look at LSF expression and if the expression is high it would indicate that the tumors are dependent on LSF for their growth and if we block LSF then the patient would have some response.
Newer combinational strategies, Dr. Sarkar said, can be developed incorporating LSF inhibitors. The Massey Cancer Center is one of 65 National Cancer Institute designated research facilities working with all kinds of cancers.
John Ogle, WCVE News