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Study identifies therapeutic target for liver cancer and predictive biomarker of response
Date:3/14/2011

Cold Spring Harbor, N.Y In a research study appearing in the journal Cancer Cell on March 14, scientists from Cold Spring Harbor Laboratory (CSHL) and four other institutions have identified a strategy for targeted molecular therapy in liver cancer, which currently has limited treatment options and one of the worst one-year survival rates of any cancer type. The researchers' experiments reveal that up to 15% of liver tumors are "driven" by the hyperactivity of a gene called FGF19, which is well known for its role in various normal biological processes such as cell growth and tissue repair. Shutting down the activity of this gene with an antibody inhibited tumor growth.

"This is an important advance considering that there are currently no genetically-targeted therapies for liver cancer," says Scott Powers, Ph.D., Director of the Human Cancer Genome Center at CSHL, who led the research team. The new study shows that this gene triggers liver cancer when it exists in multiple copies, well in excess of the normal two per cell. "It turns out that liver tumor cells with this FGF19 amplification are strongly dependent upon the gene's continued expression to sustain tumor growth."

This so-called oncogene dependency, in which cancer cells start to rely exceedingly on a single oncogene, is a molecular Achilles heel that cancer researchers are trying to exploit as a strategy for an anti-cancer weapon. This approach has been successful, for instance, by others in targeting breast cancers that have multiple copies of the HER2 gene.

The new study also highlights a powerful strategy that the scientists devised to identify the underlying driver genes that lurk within human cancer "amplicons" sizeable segments of a cell's genome that get inadvertently multiplied or amplified, thereby increasing the number of copies of genes that are present within. The strategy, known as oncogenomic cDNA screening, is an extension of an approach developed pr
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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

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