Dietary Adjustments Could Offer New Hope in Brain Cancer Treatment

Glioblastomas represent the most lethal type of malignant brain tumor, with patients typically surviving only one to two years after diagnosis. These tumors arise when normal brain cells become aggressive and invade surrounding tissue. The cancer cells exhibit distinct metabolic characteristics compared to their healthy counterparts.

A recent study published in Nature by researchers from the University of Michigan explored glucose utilization within glioblastoma tumor cells.

The team, comprising members from the Rogel Cancer Center, Department of Neurosurgery, and Department of Biomedical Engineering, found that brain tumors vary in their consumption of specific dietary nutrients.

"By modifying the diet of mouse models, we were able to significantly slow down and even halt the growth of these tumors," stated co-senior author Daniel Wahl, M.D., Ph.D., an associate professor of radiation oncology. "Our findings may pave the way for new treatment opportunities for patients in the near future."

Traditional treatments involve surgery followed by radiation therapy and chemotherapy. However, tumors often recur and develop resistance to these therapies. Previous research has linked this resistance to metabolic reprogramming within cancer cells.

Metabolism refers to the body's process of breaking down molecules like carbohydrates and proteins for energy or to build new compounds.

While both brain and cancer cells rely on sugar, the team investigated if they utilize it differently. They administered labeled glucose to mice and brain cancer patients to track its usage.

"To genuinely understand these cancers and enhance treatments, we had to study the tumors in patients rather than just in labs," said co-senior author Wajd Al-Holou, M.D., a neurosurgeon who co-directs the Michigan Multidisciplinary Brain Tumor Clinic.

"Although both normal tissues and tumor cells consume large amounts of sugar, they use it for different purposes," noted Andrew Scott, Ph.D., a research scholar in Wahl's lab. "Think of it as a metabolic fork in the road: healthy brain cells channel sugar into energy production and neurotransmission, but tumors reroute sugar to fuel their growth."

The study revealed that while normal tissues use sugars for energy and essential chemicals, glioblastomas shift these processes to produce molecules like nucleotides—critical components of DNA and RNA—that support tumor growth and invasion.

The researchers discovered additional key differences: normal brain cells utilize sugar to synthesize amino acids (the building blocks of proteins), whereas brain cancers seem to deactivate this pathway and acquire these amino acids directly from the blood.

Intrigued by this discovery, they tested whether reducing specific amino acid levels in the blood could impact brain tumor progression. When mice were fed diets limited in amino acids serine and glycine, they responded better to radiation and chemotherapy, leading to reduced tumor growth compared to control mice that received serine.

"Removing serine and glycine from the diet improved treatment responses in our mouse models," said co-senior author Deepak Nagrath, Ph.D., a professor of biomedical engineering.

The team combined these findings with mathematical models that track glucose usage across various pathways, potentially identifying new drug targets.

"Co-senior author Costas Lyssiotis, Ph.D., professor of molecular and integrative physiology, likened metabolic pathways to roads and drugs to roadblocks. "Blocking a heavily trafficked highway has greater impact than obstructing a quiet country lane," he observed.

"In the brain, blood-derived serine intake is like a minor road; in cancer, it resembles a crowded freeway, providing an opportunity for targeted therapeutic interventions."

The team plans to initiate clinical trials soon to test if diets restricting blood serum levels can assist glioblastoma patients. "This is a collaborative multidisciplinary effort," Wahl said.

"It's a research endeavor that no single investigator could accomplish alone, and I'm grateful to be part of a team dedicated to making crucial findings that enhance patient treatments."