Yue Xiong has a strong connection to his undergraduate alma mater, Fudan University, a top research institution in Shanghai, China.
During frequent trips each year to the auld sod, the William R. Kenan Jr., Distinguished Professor of Biochemistry and Biophysics at UNC School of Medicine helped develop a molecular and cell biology research lab at Fudan U. and supervises graduate student training and project development there.
Xiong’s work at UNC Lineberger Comprehensive Cancer Center, including his interest in mammalian cell cycle control and tumor suppression, has helped shape a study largely conducted at Fudan U. that shows how a particular gene mutation contributes to tumor growth.
The study also has identified a compound that could be modified to treat one of the most deadly types of cancer, a type of brain tumor called secondary glioblastoma multiforme (GBM). GBMs are part of a larger group of brain tumors called malignant gliomas, which is the type of cancer that afflicts Senator Edward Kennedy. A report of the research appeared April 10 in Science.
In experiments with tumor cells, the researchers reversed the effects of a mutation in a gene called isocitrate dehydrogenase-1 (IDH1) by replenishing a compound called α-ketoglutarate (α-KG).
“When the IDH1 gene is mutated, the level of α-KG is reduced, which in turn contributes to tumor growth by helping to increase the supply of nutrients and oxygen to tumor cells. When we added the α-KG to tumor cells, the effects caused by the IDH1 mutation were reversed,” Xiong said. “If scientists can develop α-KG into a clinical drug, it could potentially be used for treating brain tumor patients who have this specific gene mutation. The α-KG compound is already there; it only needs to be modified to be used clinically, so that may save a lot of time.”
Xiong along with Kun-Liang Guan, Ph.D., professor of pharmacology at the University of California, San Diego, are corresponding authors of the study.
The findings and potential treatment apply mostly to secondary GBM, rather than a different type of tumor called primary GBM. About 75 percent of secondary GBMs have mutations in the IDH1 gene, but only 5 percent of primary GBMs have this mutation, Xiong said. Even though these two types of GBM have a similar end result, the tumor types develop in very different ways, and doctors will need very different treatments to stop them.
Xiong says he and his colleagues are continuing studies of other effects of the IDH1 mutation and are developing a mouse model of secondary GBM that could be used to test the potential treatment. The Shanghai connection continues.