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New York, June 6 -- A protein called Stat3 may be the target for new therapies to fight cancer, according to a new study led by NYU School of Medicine researchers. In the study, published in the June issue of the journal Nature Medicine, human tumors that had been transplanted into mice disappeared after the Stat3 protein had been shut down in the tumors.
The study was led by David E. Levy, Ph.D., Professor of Pathology and Microbiology, and Giorgio Inghirami, M.D., Associate Professor of Pathology.
“We have shown that this protein is essential for the survival of tumor cells but not for normal tissue,” says Dr. Levy. “Although our results were obtained from studies in mice, the results suggest that our approach can be extended to the treatment of human malignancies.”
In the new study, the researchers used a snippet of DNA called an antisense oligonucleotide to block the activity of Stat3. The drug, which was provided by the biotechnology company ISIS Pharmaceuticals based in Carlsbad, Calif., scrambles the cell’s machinery that is necessary to produce the protein. The researchers injected this drug into mice that had been transplanted with human lymphomas, a type of cancer of white blood cells. Over a period of a few days, the tumors simply melted away, says Dr. Inghirami. The drug also prevented any tumor growth if it was injected at the same time as the tumors were transplanted into the mice.
It is far too early to know whether drugs that block Stat3 production will ever become cancer therapies, but at least two pharmaceutical companies are already interested in developing a drug that was used in the study to turn off Stat3, according to Drs. Levy and Inghirami.
The researchers plan to identify the aspects of tumor growth and survival that are directly dependent on Stat3 activity. They hope these further studies will allow the development of more precise and effective anti-cancer drugs based on the unique action of the protein in tumor cells.
Over the last 10 years, abnormally active forms of Stat3 (which stands for “signal transducers and activators of transcription”) have been found in a wide variety of human cancers, ranging from head and neck to breast, prostate, and blood. Dr. Levy and his colleagues have been studying Stat3 since the mid 1990s, when they first cloned its gene. So far seven Stats have been identified in mammals. Meanwhile, Dr. Inghirami has focused his laboratory studies on a group of cancers, called anaplastic large cell lymphoma, which mainly affect children.
Stats act as gofers between the outside of the cell and its nucleus, the organelle where gene expression takes place. These messengers tell the cell how to respond to external stimuli, especially to events that require an immune response. Many of the complex details about how Stats are regulated in cells and the processes that they in turn regulate are still being worked out. But it is known that some of these proteins respond to immune stress, such as when a pathogen enters a body, while others play roles in diverse biological functions, such as lactation, hematopoiesis (formation of blood cells), and skeletal development.
The authors of the new study are Roberto Chiarle, William J Simmons, Honjying Cai, Girish Dhall, Regina Raz, Dr. Inghirami and Dr. Levy, who are all affiliated with NYU; James Karras from ISIS Pharmaceuticals; and Alberto Zamo from the University of Verona.
The study can be accessed online at the following url: http://www.nature.com/nm/journal/v11/n6/full/nm1249.html.
An editorial, entitled “Validating stat3 in cancer therapy,” by James E. Darnell Jr. of Rockefeller University accompanies the article. The editorial is found at: http://www.nature.com/nm/journal/v11/n6/full/nm0605-595.html.
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