Scientists have been trailing the mutation since its discovery in 2008, and this recent discovery at University of North Carolina Lineberger Comprehensive Cancer Center may yield potential ways to counter its effects. Yue Xiong, PhD, and William R. Kenan Jr. professor of biochemistry and biophysics, said investigators now know IDH (the mutated gene) "represents the most frequently mutated metabolic gene in human cancer."
About a third of patients with low-grade brain tumors and 20 percent of patients with acute myeloid leukemia have the mutated IDH gene, which help metabolize food. Scientists discovered that the IDH mutation spurs a battle between two metabolites (tiny molecules produced by metabolic enzymes) inside cells. This battle leads to both normal cell growth and cancerous cell growth.
Cells with the IDH mutation produce fewer of the molecules responsible for normal cell growth (α-KG) and more of the cancer-causing molecules (2-HG). Eventually the cancerous molecules overcome the healthy molecules and disable a whole family of enzymes that depend on α-KG to do their job of normal cell growth.
To make matters worse, if 2-HG (cancer-causing molecules) wins the battle, 2-HG can also activate other genes that lead to cancer growth.
So now researchers are looking to develop one of two potential therapies, one that disrupts the ability of the mutant enzyme from producing 2-HG or another in which researchers provide α-KG (the molecules responsible for normal cell growth) to patients with mutated IDH to combat 2-HG molecules.
More than 13,000 people died from brain and nervous system cancers in the United States last year, and more than 20,000 died of leukemia.