Amino Acids May Lead to Improved Survival in Glioblastoma

Dietary intake of methionine and tryptophan may slow brain cancer tumor progression.

A recent study found 2 amino acids that abnormally metabolize are essential to the development of glioblastoma (GBM) and could lead to alternative treatment approaches for this aggressive brain cancer.

The altered metabolism of methionine and tryptophan occurs because of the loss of key enzymes in GBM cells. This causes oncogenes to activate and tryptophan’s metabolism to shield GBM cells from detection, leading to the progression of tumor growth and cancer cell survival.

“Our findings suggest that restricting dietary intake of methionine and tryptophan might help slow tumor progression and improve treatment outcomes,” said first study author Kamalakannan Palanichamy, PhD.

Although more research needs to be done to understand exactly how the metabolites activate oncogenic proteins, the findings suggest novel therapeutic targets for brain cancer.

“For example, restoring the lost enzymes in the 2 metabolic pathways might slow tumor progression and reduce aggressiveness by inactivating oncogenic kinases and activating immune responses,” said principal investigator and study leader Arnab Chakravarti, MD.

The study, published in Clinical Cancer Research, used 13 primary GBM cell lines from patient tumors, 4 commercially available GBM cell lines, and normal human astrocyte cells.

The results of the study showed several key findings: GBM cells concentrate methionine 5 to 100 times more than normal human astrocytes; GBM cells growing without methionine slowed proliferation 40% to 60%; abnormal metabolism of methionine lead to aberrant methylation and gene silencing; and reinforcing kynurenine catabolic enzymes in the tryptophan pathway could enable the immune cells to recognize and destroy GBM cells.

Researchers believe that because GBM cells take up methionine faster than normal glioma cells, the positron emission tomography, which uses methionine as a tracer (MET-PET), could help map GBM tumors more accurately, allowing for more precise surgical removal and radiation therapy planning.