Researchers identify primary driver of stomach cancer development

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Washington, Apr 23 : Scientists have raised hopes for the development of new treatments for gastric cancer, by discovering what appears to be the key driver of tumour development in the stomach.

Scientists at the Melbourne Branch of the international Ludwig Institute for Cancer Research (LICR) showed that inhibition of the signalling cascade triggered by the IL-11 protein prevented the development of inflammation, hyperplasia (an abnormal increase in the number of cells) and tumor formation in pre-clinical models of gastric cancer.

It is well known that gastric cancer is the second most common cause of cancer-related deaths around the world, and has also been shown to be correlated with chronic inflammation.

Constant activation of the Stat3 protein, which is known to play roles in inflammation-associated carcinogenesis, is commonly found in gastric and many other types of cancer. However, the underlying cause of hyperactive Stat3 was unknown, until now.

In the current study researchers have shown that IL-11 promotes chronic inflammation and associated tumorigenesis in the stomach by inducing excessive activation of Stat3.

Using both genetic and pharmacologic inhibitors, the study showed that blocking this signalling pathway prevented or reduced tumorigenesis in a mouse model of inflammation-dependent human gastric cancer.

"Although we made this discovery in a mouse model, we expect it to be highly relevant to the clinic because of the striking similarity in gastric tumour development and appearance between mice and men," Professor Matthias Ernst from the LICR Melbourne Branch, and the lead author of the study.

He added: "The clear link between inhibition of IL-11/Stat3 activity and suppression of gastric tumorigenesis that we identified supports the further development of pharmacologic agents that target these molecules for the treatment of gastric and potentially other cancers. We believe that we have a very relevant model in our hand for the preclinical assessment of such compounds as well as for the identification of potential markers that may ultimately help in the early detection of disease."

The study is published on-line in the Journal of Clinical Investigation.

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