A particularly aggressive form of brain tumor called a glioma may be vulnerable to a drug currently used to treat Crohn's disease, according to a new study in mice. The finding is good news to scientists looking for better treatment options for a cancer that is almost always fatal.
The drug exploits a weakness of glioma cells. While most cells take in a necessary amino acid called cystine through a variety of pathways, a team led by Harald Sontheimer, a neuroscientist with the University of Alabama at Birmingham, has discovered that glioma cells have only one mechanism for grabbing the amino acid. Earlier studies elsewhere found that cystine intake in leukemia cells is impaired by sulfasalazine, a drug used to treat diseases such as Crohn's, which causes inflammation of the intestinal tract. So, Sontheimer and colleagues wondered if the drug would cut off the cystine supply to glioma tumors.
To test the theory, the researchers first injected mice with malignant human glial tissue. After the tissue developed into tumors, the team divided the mice into three groups. Two groups got sulfasalazine for either 1 or 3 weeks, and a control group received saline. Within 48 hours of receiving the drug, mice in the sulfasalazine group showed biochemical signs that glioma cells were affected. And within a matter of weeks, the size of their tumors had shrunk dramatically. The drug also increased the animals' survival rate. Mice in the control group showed no improvement, the team reports 27 July in the Journal of Neuroscience.
Cells need cystine to produce a substance called glutathione, which binds the free radicals generated by energy-producing mitochondria. If cancer cells can't make glutathione, free radicals can destroy the cell membrane, damage DNA, and impede energy production. Sontheimer expects to see the same vulnerability in other types of cancer. Still, many questions remain unanswered, Sontheimer notes, including how much of the drug would be needed to treat a human--or if it would even fight gliomas.
"This is very thorough research, and it's welcome news for the field," says Waldemar Debinski, a cancer biologist at Wake Forest University Baptist Medical Center in Winston-Salem, North Carolina, and a glioma expert. "But talking about research is one thing; talking about the use of the drug is a bit premature."