Researchers have identified a complex of proteins that promotes the growth of some types of colon and gastric cancers, and shown that medications that block the function of this complex have the potential to be developed into a new treatment for these diseases.
The complex of proteins, known as mTorc1 (mammalian target of rapamycin complex 1), has previously been implicated in the development of some other cancers but this is the first time it has been shown to promote the growth of colon and gastric cancers that are associated with inflammation.
Dr Stefan Thiem and Associate Professor Matthias Ernst from the Walter and Eliza Hall Institute's Cell Signalling and Cell Death division made the discovery with colleagues while at the Melbourne-Parkville Branch of the Ludwig Institute for Cancer Research. Associate Professor Ernst is a Ludwig Institute Member. Their findings are published online January 17 in the Journal of Clinical Investigation.
Cancers of the digestive system are a significant cause of death in Australia. Colon (or bowel) cancer causes more than 4000 deaths annually -- more than any other cancer except lung cancer -- while more than 1000 Australians die from gastric (or stomach) cancer each year.
Associate Professor Ernst said many types of colon and gastric cancer were associated with chronic inflammation. "We have previously shown that the immune system's inflammatory response can promote the growth of tumours," he said. "In the digestive system, persistent inflammatory conditions have been linked with tumour growth: patients who have stomach ulcers or gastritis (inflammation of the stomach lining) are more susceptible to gastric cancer, while inflammation of the colon, called colitis, is associated with an increased risk of developing colon cancer."
The research team found that inflammation-associated gastric and colon cancers showed activation of mTorc1, an aggregate of proteins that signals inside cells to promote growth. Many cancer types depend on mTorc1 activity to grow, and there is considerable interest in the use of mTorc1 inhibitors to treat cancer.
The growth of inflammation-associated colon and gastric cancers could be treated with mTorc1 inhibitors, Associate Professor Ernst said. "We were excited to discover that the growth of these cancers in laboratory models could be prevented by treatment with mTorc1 inhibitors that are already in clinical trials for other types of cancer," he said. "In the future, we hope that this finding might lead to better treatment options for colon and gastric cancers that are associated with inflammation. Since there are also other types of cancer that are associated with inflammation, we suspect that these could also be susceptible to treatment with mTorc1 inhibitors."
The research was supported by the Australian National Health and Medical Research Council and the Victorian Government.
- Stefan Thiem, Thomas P. Pierce, Michelle Palmieri, Tracy L. Putoczki, Michael Buchert, Adele Preaudet, Ryan O. Farid, Chris Love, Bruno Catimel, Zhengdeng Lei, Steve Rozen, Veena Gopalakrishnan, Fred Schaper, Michael Hallek, Alex Boussioutas, Patrick Tan, Andrew Jarnicki, Matthias Ernst. mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice. Journal of Clinical Investigation, 2013; DOI: 10.1172/JCI65086
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