Published discovery may lead to new therapy for bile duct cancer affecting the liver
Dr. Sergio Gradilone and team at The Hormel Institute’s Cancer Cell Biology and Translational Research lab published breakthrough cancer research in the high impact journal Hepatology. Dr. Gradilone led the research team that included Drs. Adrian P. Mansini, Estanislao Peixoto and researchers Sujeong Jin and Seth Richard.
“This discovery is critically important because it uncovers novel information on fundamental, ciliary-dependent mechanisms controlling the spread of malignant cells, and provides the foundation for novel anti-cancer therapies,” said Dr. Gradilone, who joined The Hormel Institute in October 2014. “This research opens the door to a potential future treatment that limits the progression of this cancer that impacts the liver. Our goal is to stop cancer’s progression and life can be protected.”
The key findings presented here relate to the novel ciliary-dependent regulation of cell migration and invasion, important characteristics tumor cells exploit to growth and metastasize to other parts of the body. The primary cilium is a hair like structure protruding from the cellular membrane and is considered the cellular antenna. Dr. Gradilone group previously described that these antennae are lost in tumor cells. The research team now found the cilium can inhibit the spread of tumor cells and identified the molecular mechanisms where a protein known as LKB1 acts as a hub regulating the external signals received by the cellular antenna. Therefore, the research team identified a naturally derived compound that can directly regulate LKB1 in tumor cells, mimicking the functions of primary cilia and inhibiting tumor growth.
Cholangiocarcinoma, or bile duct cancer, is a lethal form of liver cancer and no effective pharmacologic therapy exists. The bile ducts are a series of thin tubes network inside the liver that ends up in an extrahepatic tube that goes from the liver to the small intestine. Bile duct cancer is somewhat rare but the actual number of cases is likely to be higher than reported because these cancers can be hard to diagnose and some might be misclassified as other types of cancer. About 8,000 people in the United States are diagnosed with it each year. Survival rates vary by location of the tumor, but 5-year survival for early stage bile duct cancers is about 15-30%, with 5-year survival for late stage bile duct cancers at about 2%.
Interestingly, the loss of primary cilia has been now described in other malignancies like breast, pancreatic, kidney, prostate, and lung cancer among others, increasing the significance of our studies.
Next steps for this research are to further test the natural compounds able to regulate LKB1 in order to translate this discovery to the patients.