The National Cancer Institute has awarded a five-year, $1.8 million grant to an Arizona Cancer Center researcher to study the role of inflammation in colon carcinogenesis and to develop a new therapy to treat colon cancer.
"People affected with Inflammatory Bowel Disease are at higher risk to develop colon cancer," said principal investigator Emmanuelle J. Meuillet, an Arizona Cancer Center member and associate professor of nutritional sciences and molecular and cellular biology at the University of Arizona.
Most of the time, the inflammation process is taken care of rapidly. For example, the redness, itchiness and swelling caused by a bee sting is typically gone in a matter of hours or days. However, for reasons not entirely understood, some people develop chronic inflammation, which can lead to inflammation-related diseases, such as cancer.
"During the process of inflammation, there are many inflammatory molecules that are produced and one of them that seems to play a detrimental role in many different types of cancers is called prostaglandin E2, or PGE2," Meuillet said. "If it's out of balance too much, it can induce tumor growth, among many other things. The last enzyme that is responsible for the synthesis of this molecule is microsomal Prostaglandin E Synthase, or mPGES-1, and that's the one we are focusing on."
A drug that inhibits mPGES-1 activity could reduce production of PGE2, which is over-expressed in many cancers and inflammatory diseases, and slow – or even reverse – tumor growth, Meuillet said. The benefit of developing therapies that target a specific protein, such as mPGES-1, is that they often have fewer side effects for patients than traditional treatments.
"With the preliminary data we have, we have a lead compound that's not toxic, that shows very good anti-tumor activity and even regression after the treatment," said Meuillet, referencing early research.
This grant will enable Meuillet and her team to:
- Use colon cancer cell lines and inflammatory colon cancer animal models to investigate mPGES-1 to find clear evidence that it plays a role in colon carcinogenesis and will be a good drug target for the treatment of colon cancer.
- Identify novel compounds that can bind to mPGES-1 and inhibit its activity and synthesize those compounds and test them in colon cancer cell lines.
- If the compounds are active in cell lines, test them in vivo for anti-tumor properties.
While this grant funds research focused on colon cancer, the findings may have widespread applications for patients with other cancers and health conditions, such as inflammatory breast cancer, pancreatitis (which can lead to pancreatic cancer) and chronic obstructive pulmonary disease (which can lead to lung cancer) as well as gingivitis and rheumatoid arthritis. It also has potential preventative applications.
"It's not only important for colon cancer," said Meuillet. "It's very important in any inflammation-derived cancer and any disease that starts with an inflammation process. These are all areas that need attention."
"The impact is huge," she said. "The possibilities are endless."
The Arizona Cancer Center is the only National Cancer Institute-designated Comprehensive Cancer Center headquartered in Arizona. With primary locations at the UA, the cancer center has more than a dozen research and education offices in Phoenix and throughout the state and 300 physician and scientist members working together to prevent and cure cancer.