STAT-3

Scientists from Isis Pharmaceuticals, Inc. in collaboration with scientists at the Department of Pathology and NYU Cancer Institute, New York University School of Medicine and the Department of Pathology and Center for experimental Research and Medical Studies (CERMS), University of Torino, have reported in Nature Medicine that the STAT-3 gene is required for the generation of B-lymphomas in mice carrying a mutation implicated in some human lymphomas and that reducing the expression of STAT-3 with a second-generation antisense drug targeted to STAT-3 resulted in impaired growth of human and mouse lymphoid tumors in animals. These results suggest that the second-generation antisense inhibitor of STAT-3 might be an effective treatment for human lymphomas, multiple myeloma, and other cancers. The drug, ISIS 345794, is in preclinical development at Isis.

"It has been known for sometime that spontaneously occurring rearrangements on genes in human chromosomes can cause some cancers. For example, in some forms of human lymphomas, a cancer-causing gene is aberrantly relocated in the chromosome and inappropriately activated. We used genetic techniques to show that in a mouse model of human lymphoma and myeloma that the loss of STAT-3 prevents progression of disease and, in some cases, reverses the growth of existing lymphomas," said Dr. Giorgio Inghirami, senior author of the publication. "Although modern genetic methods can lead to important insights into diseases, one of the central challenges is to rapidly convert the information to new drugs that will benefit patients. Antisense technology gives researchers the ability to target a specific protein, such as STAT-3, to clearly determine its pathogenetic role, and to efficiently treat the cause of the disease."

"This study was one of the studies that supported our understanding of the biological function of STAT-3 and reinforced our enthusiasm for this very exciting drug. Through the use of antisense technology, we confirmed with our collaborators that inhibition of STAT-3 prevented the progression of cancer," said Brett P. Monia, Ph.D., Isis' Vice President of Antisense Drug Discovery. "Once we have a functional understanding of a particular molecular target, we can progress the specific antisense inhibitor used to validate the target rapidly into drug development. ISIS 345794 is an excellent example of the value and efficiency of the technology for the treatment of human disease."