A team of researchers at Ben-Gurion University has unveiled a novel approach to treating brain cancer by targeting the survival mechanisms of tumor cells under glucose starvation.

Their findings, published May 14 in Nature Communications, suggest that accelerating the metabolic processes of tumor cells during glucose starvation could cause them to quickly exhaust their energy supplies and die.

Research head Prof. Barak Rotblat, along with co-lead researcher Gabriel Leprivier of the Institute of Neuropathology at University Hospital Düsseldorf, discovered that tumors have less glucose compared to normal tissue.

This observation challenges the belief that cancer cells are primarily focused on rapid proliferation. Instead, the researchers propose that the top priority of cancer cells might be survival rather than growth. Triggering a burst of growth under glucose starvation could lead to the cells running out of energy.

Cells regulate their growth based on energy availability, synthesizing fats and proteins when energy is plentiful and halting these processes when energy is scarce to avoid burning out.

Tumors are often in a state of glucose starvation. By identifying and disabling the molecular mechanisms that enable their survival under these conditions, the researchers aim to selectively target cancer cells while sparing healthy ones.

“We may be able to target just the cancer cells and not regular cells at all, which would be a very promising step forward on the path to personalized medicine and therapeutics that do not affect healthy cells the way chemotherapy and radiation do,” Rotblat explained.

The team focused on the mTOR (Mammalian Target of Rapamycin) pathway, which plays a key role in regulating cell growth based on energy levels.

They identified a protein within this pathway, 4EBP1, as essential for cells to survive glucose starvation. 4EBP1 inhibits the enzyme ACC1 in the fatty acid synthesis pathway, a mechanism that cancer cells exploit to thrive in low-glucose environments.

“Our discovery about glucose starvation and the role of antioxidants opens a therapeutic window to pursue a molecule which could treat glioma [brain cancer],” Rotblat noted.

The potential application of this research could extend to other types of cancers.

Rotblat’s team is now collaborating with BGN Technologies (BGU’s tech-transfer company) and the National Institute for Biotechnology in the Negev to develop a molecule that will block 4EBP1.

This intervention would force glucose-starved tumor cells to continue synthesizing fats, depleting their energy reserves and leading to cell death.

The research highlights a new direction in the pursuit of cancer treatments that target cancer cells specifically, offering a potential alternative to conventional treatments such as chemotherapy and radiation that affect healthy cells.