Glioblastoma is the most common type of brain tumor in adults. The disease is 100% fatal and there are no cures, making it the most aggressive type of cancer. Such a poor prognosis has motivated researchers and neurosurgeons to understand the biology of tumors with the goal of creating better therapies.
Dominique Higgins, MD, PhD, an assistant professor in the Department of Neurosurgery, has heeded the call. Higgins and a team of researchers at Columbia University have found that glioblastoma tumor cells are particularly sensitive to ferroptosis – a type of cell death that can be triggered by removing certain amino acids from the diet.
“First, we found that when we take away certain amino acids in animal models that the glioblastoma cells are more likely to die by ferroptosis,” said Dr. Higgins. “Secondly, we found that removing these amino acids makes our drugs a lot more effective at inducing ferroptosis in cancer cells.”
Their findings were published in Nature Communications.
Ferroptosis is an iron-dependent type of “programmed cell death” or a biological process that causes cells to “self-destruct” on command. Our bodies don’t need to kill cells unless absolutely necessary, so the process is tightly controlled by certain biological mechanisms. However, researchers are only now beginning to comprehend the process because ferroptosis was recognized within the past decade.
“The recent discovery of ferroptosis adds to the excitement of it all,” said Higgins, who is a member at the UNC Lineberger Comprehensive Cancer Center. “It is really a rapidly growing body of research, and we are finding that it’s a very important for a lot of biological processes, and not just in cancers.”
Every cell has certain safety features to keep it from going through ferroptosis in an unpredictable way. Two amino acids, cysteine and methionine, are critical for preventing the process from starting in cells. We typically pick up these amino acids through our diet.
Therefore, Higgins and his research team decided to focus their efforts on these components.
By depriving animal models of cysteine and methionine through a customized diet, they found that the glioblastoma cells were significantly more likely to die via ferroptosis. They also found that the diet made their chemotherapy drugs more apt at initiating programmed cell death, meaning that very low doses were able to achieve a more potent effect than before. Ultimately, the animal models had improved survival after going on the diet.
