Unraveling a Stomach Cancer Puzzle

Newswise — It started several years ago with the observation that a large group of seemingly unconnected genes were behaving differently in patients with stomach cancer. Now a multi-national research team led by the Melbourne Branch of the Ludwig Institute for Cancer Research (LICR) has joined the proverbial dots and identified a potential new target for stomach cancer therapy, according to a paper published today in the prestigious Nature Medicine journal.

The paper's first author, LICR's Dr. Brendan Jenkins, says that this single study has made several substantial contributions to the understanding of Stat3, the protein linking those 'genes behaving badly' and central to development, tissue equilibrium and the immune system. "We showed that, in mice, hyperactive Stat3 shuts down a vital controller of stomach cell growth, called TGF beta, and this allows cancer formation, and this mechanistic link is a world-first. Also, the gene differences identified in human stomach cancers are similar to those we would predict if the same thing, Stat3 hyperactivity shutting down TGF, happens in humans. So this is also the first time a connection between stomach cancer and this signaling pathway has been made."

Team leader Dr. Matthias Ernst, also from LICR, says that these basic research findings may one day impact directly on the treatment of stomach and other cancers. "We've demonstrated that by lowering Stat3 hyperactivity we can suppress stomach cancer formation, importantly without affecting Stat3's other important roles in the body. Add to that the evidence suggesting that Stat3 is also involved in breast, head and neck, and prostate cancers, and we have a compelling case for investigating the development of therapies that target Stat3."

This study was performed by investigators from: Melbourne Branch, Ludwig Institute for Cancer Research, Melbourne, Australia; Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Pathology, Peter MacCallum Cancer Institute, Melbourne, Australia; Department of Medical Biochemistry and Immunology and Institute of Nephrology, Cardiff University School of Medicine, Cardiff, UK; and Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York, USA.

The Ludwig Institute for Cancer Research (LICR) is the largest international academic institute dedicated to understanding and controlling cancer. With ten Branches in seven countries, and numerous Affiliates and Clinical Trial Centers in many others, the scientific network that is LICR quite literally covers the globe. The uniqueness of LICR lies not only in its size and scale, but also in its philosophy and ability to drive its results from the laboratory into the clinic. LICR has developed an impressive portfolio of reagents, knowledge, expertise, and intellectual property, and has also assembled the personnel, facilities, and practices necessary to patent, clinically evaluate, license, and thus translate, the most promising aspects of its own laboratory research into cancer therapies.