Lineberger researchers identify compound that may stop deadly brain tumors

Thursday, April 9, 2009 — A research team led by Yue Xiong, Ph.D., professor of biochemistry and biophysics and a member of the UNC Lineberger Comprehensive Cancer Center, has identified a compound that could be modified to treat one of the most deadly types of cancer.

Lineberger researchers identify compound that may stop deadly brain tumors click to enlarge Yue Xiong, Ph.D.

A research team led by Yue Xiong, Ph.D., professor of biochemistry and biophysics and a member of the UNC Lineberger Comprehensive Cancer Center, has identified a compound that could be modified to treat one of the most deadly types of cancer.  They have also discovered how a particular gene mutation contributes to tumor growth.

The findings and potential treatment apply 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 from which Senator Edward Kennedy suffers.

A report of the research will appear in the April 10 issue of the journal Science.

In laboratory 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 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,” said Xiong.

Essentially, the compound helped ‘starve’ the tumor cells, stunting their growth.

“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 said.

Xiong is a corresponding author of the study along with Kun-Liang Guan, professor of pharmacology, at the University of California, San Diego.

Xiong and Guan helped develop the lab at Fudan University and supervise graduate student training and project development there.

Xiong and 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, paving the way for eventual clinical trials in humans.

The current study was supported by the National Institutes of Health, the Chinese Ministry of Education, State Key Development Programs of China, National 863 Program of China, China NSF grants, and Shanghai Key Basic Research Projects.

 

Lineberger Center contact: Dianne Shaw, (919) 966-7834, dgs@med.unc.edu
School of Medicine contact: Les Lang, (919) 966-9366, llang@med.unc.edu
UNC News Services contact: Patric Lane, (919) 962-8596, patric_lane@unc.edu

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