Therapeutic target for gastric cancerDec. 12, 2013, 11:30 AM
Chronic inflammation contributes to the development of gastric cancer, the second leading cause of cancer-related deaths worldwide. Aurora kinase A (AURKA) is frequently overexpressed in gastrointestinal and other cancers, but its roles in inflammation and tumorigenesis are unclear.
Wael El-Rifai, M.D., Ph.D., professor of Surgery, and colleagues have now linked AURKA overexpression to inflammation. They demonstrated that increased AURKA expression correlates with increased levels of pro-inflammatory molecules (including NF-kappaB) in the gastric mucosa of a mouse model that develops gastric cancer, and in gastric tissue samples from patients with pre-malignant and malignant lesions.
They showed that inhibition of AURKA reduces NF-kappaB activity in gastric cancer cells, reduces xenograft tumor growth, and reverses the development of gastric tumors in the mouse model. They found that AURKA activates NF-kB by directly binding to and modifying the NF-kB regulator, IkB.
The findings, reported in the December issue of Gastroenterology, highlight the importance of AURKA in gastric tumorigenesis and support the potential of AURKA inhibitors as therapeutic agents for gastric cancer.
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