Chemical compound that may stop brain tumours
8 May 2009
Researchers at the University of North Carolina at Chapel Hill School
of Medicine have identified a compound that could be modified to treat
one of the most deadly types of cancer, and discovered how a particular
gene mutation contributes to tumour growth.
The findings and potential treatment apply to a type of brain tumour
called secondary glioblastoma multiforme (GBM). GBMs are part of a
larger group of brain tumours called malignant gliomas, which is the
type of cancer Senator Edward Kennedy suffers from.
A report of the research was published in the April 10, 2009 issue of
the journal Science.
In experiments with tumour 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,” said Yue
Xiong, Ph.D., William R. Kenan Jr., Distinguished Professor of
Biochemistry and Biophysics and a member of the UNC Lineberger
Comprehensive Cancer Center.
“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, Ph.D., professor of pharmacology at the University of California,
The findings and potential treatment apply mostly to secondary GBM,
rather than a different type of tumour 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 tumour types
develop in very different ways, and doctors will need very different
treatments to stop them.
The first author of the Science paper is Shimin Zhao, Ph.D., of Fudan
University in Shanghai, China. Zhao and students in his lab made key
contributions to the research, Xiong said. Those students, also authors
on the paper, are Yan Lin, Wei Xu, Wenqing Jiang, Zhengyu Zha, Pu Wang,
Wei Yu, Zhiqiang Li, Lingling Gong, Yingjie Peng, Jianping Ding and
Xiong and Guan helped develop the lab at Fudan University and
supervise graduate student training and project development there.
Xiong 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 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.
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