Novel Synthetic Small Molecule Inhibits Activity of Protein That Promotes Both Breast Cancer and Pancreatic Cancer

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have identified a novel synthetic compound that sharply inhibits the activity of a protein that plays an important role in in the progression of breast and pancreatic cancers. In the new study, published online on December 3, 2014 in the journal Molecular Pharmacology, the scientists showed that the compound, known as SR1848, reduces the activity and expression of the cancer-related protein called "liver receptor homolog-1" or LRH-1. "Our study shows that SR1848 removes LRH-1 from DNA, shutting down expression of LRH-1 target genes, and halts cell proliferation," said Dr. Patrick Griffin (image), Chair of the TSRI Department of Molecular Therapeutics and Director of the Translational Research Institute at Scripps Florida. "It's a compound that appears to be a promising chemical scaffold for fighting tumors that are non-responsive to standard therapies." LRH-1 plays a crucial role in breast cancer through its regulation of genes involved in hormone synthesis and cholesterol metabolism--also key risk factors in cardiovascular disease. LRH-1 has also been implicated as a tumor promoter in intestinal and pancreatic cancer. Overexpression of LRH-1 has been shown to promote invasiveness and metastasis, which usually lead to the lethal spread of the disease. "LRH-1 has been implicated in the proliferation and metastasis of estrogen receptor-positive breast cancers and the more difficult to treat estrogen receptor-negative breast cancers," said Research Associate Dr. Alex Corzo, the first author of the study.
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