Researchers at Lund University have identified a previously unknown defense mechanism employed by aggressive brain tumors, revealing a sugar-rich shield surrounding cancer cells that protects them from a destructive form of cell death. The discovery, published in Nature Cell Biology on February 11, 2026, could pave the way for more effective treatments for glioblastoma and other central nervous system cancers.
Glioblastoma, a particularly aggressive form of brain cancer, is characterized by its ability to evade the body’s immune response and resist conventional therapies. Tumors develop in an extreme environment marked by oxygen deprivation, nutrient scarcity, low pH levels, and chronic cellular stress. Despite these harsh conditions, cancer cells adapt and survive, often proving resistant to existing treatments.
The research team, led by Professor Mattias Belting of Lund University and an attending physician in neuro-oncology at Skåne University Hospital, found that tumor cells construct a protective layer composed of complex sugar molecules, primarily a structure called chondroitin sulfate. This “sugar shield” acts as a filter, limiting the uptake of fat particles that, within the tumor’s environment, can become toxic.
“This changes our understanding of how aggressive cancer adapts to survive in the extreme tumor environment in the brain,” said Professor Belting. The shield prevents a process known as ferroptosis, a particularly destructive form of cell death triggered by the oxidation of fats within the cell.
In addition to the sugar shield, the researchers discovered that tumor cells also store fat in droplets within the cell itself, creating a secondary defense mechanism. These droplets serve as a reservoir, capturing harmful fats and preventing them from causing cellular damage.
“We observed that these two mechanisms – the sugar shield and the fat droplets – work together,” explained Anna Bång-Rudenstam, a doctoral student and medical student at Lund University, and first author of the study. “we wanted to investigate what happens when you disrupt both simultaneously.”
The researchers developed experimental strategies to inhibit the formation of chondroitin sulfate, effectively dismantling the sugar shield, and simultaneously blocked the cells’ ability to store fat in droplets. In experiments, disrupting both defenses caused the tumor cells to collapse. Without the shield to block harmful fats and the droplets to store them safely, the cells rapidly underwent ferroptotic cell death.
“The experimental combination treatment attacks the tumor cells’ defense mechanisms,” said Bång-Rudenstam. “When they disappear, the tumor cells become sensitive to oxidized fats that cause ferroptotic cell death.”
The findings are based on analyses of tumor material from patients, including cells isolated directly after brain surgery, and so-called organoids – minor, three-dimensional tumor models that more accurately reflect tumor behavior in patients. The researchers also observed the same sugar shield in metastases that had spread to the central nervous system from malignant melanoma, lung cancer, and kidney cancer.
The study involved collaboration between researchers at Lund University, Umeå University, Uppsala University, and the University of California, San Diego. Researchers at Uppsala University previously identified a method to help immune cells penetrate brain tumors, a finding published in Cancer Cell in May 2023, but this new research focuses on a distinct tumor defense mechanism.
Professor Belting stated that the team hopes their work will ultimately lead to the development of new, more effective treatments for patients battling these aggressive cancers.
