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 tumor growth.
The findings and potential treatment apply to a type of brain tumor called secondary glioblastoma multiforme (GBM). GBMs are part of a larger group of brain tumors called malignant gliomas.
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 ?-ketoglutarate (?-KG).
‘When the IDH1 gene is mutated, the level of ?-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 ?-KG to tumor cells, the effects caused by the IDH1 mutation were reversed,’ said Yue Xiong, PhD, William R. Kenan Jr. Distinguished Professor of Biochemistry and Biophysics and a member of the UNC Lineberger Comprehensive Cancer Center.
‘If scientists can develop ?-KG into a clinical drug, it could potentially be used for treating brain tumor patients who have this specific gene mutation. The ?-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.
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 five 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.
Release Date: April 9, 2009
Source: University of North Carolina School of Medicine
