As new findings about tumors and glucose starvation have opened a therapeutic window

Glucose (sugar) is one of the most important nutrients, and its shortage in living organisms represents a cardinal physiological stress. In fact, glucose deprivation compels cells to evolve molecular mechanisms to adjust their metabolism and sustain survival. These mechanisms are particularly critical for cells residing within solid tumors, as these tissues suffer from glucose deprivation due to defective vascularization.

If the brakes on a race car were disabled, it would quickly crash on the runway. Prof. Barak Rotblat of Ben-Gurion University of the Negev (BGU) in Beersheba wants to do something similar to brain cancer cells so they can die by disabling their ability to survive the lack of glucose. 

In fact, with his novel approach to brain cancer, he wants to speed the tumor cells up, so they just as quickly be destroyed. out. It is a novel approach to brain cancer based on a decade of research in his lab.  

Co-research with Dusseldorf

Rotblat studies the molecular biology of cancer by examining the role of long non-coding RNAs and regulators of mRNA translation. Among other functions, long non-coding RNAs control regulation in cells. Protein content analysis shows that a cancerous cell is very similar to a normal cell from the same tissue; for example, a cancerous breast cell is more similar to a breast cell than to a cancerous cell in the lung. But while the protein profiles of healthy and cancerous cells from a given tissue are very similar, their llong-coding RNAs’ content is very different. Therefore, lncRNA represents a promising drug and therapeutic target. 

He and his students and co-head researcher, Dr. Gabriel Leprivier of the Institute of Neuropathology at University Hospital Düsseldorf have just published their findings in the prestigious journal Nature Communications ITALICS under the title “mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism.” 

Brain tumors are very dependent on glucose (sugar) to develop, but they are exposed to glucose-deprived conditions within their microenvironment as a consequence of high consumption of glucose and a poor supply of nutrients. As a result of cellular adaptation to such stress. These conditions can result in the emergence of highly aggressive cancer-cell clones. 

Until now, it was believed that cancer cells prioritized growth and rapid proliferation and that there is less glucose in tumors compared to normal tissue. If cancer cells are solely focused on reproducing at the fastest possible rate, then they should be more dependent on glucose than regular cells. But if their absolute top priority is survival rather than exponential growth, triggering a burst of growth under sugar starvation could lead to the cell running out of energy to survive and dying out. 

“It’s an intriguing insight that comes after a decade of research,” Rotblat noted. “We may be able to target just the cancer cells and not regular cells at all; this 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.”

He added that his team’s discovery about glucose starvation and the role of antioxidants “opens a therapeutic window to pursue a molecule that could treat glioma (brain cancer). Such a therapeutic might also be able to treat other types of cancers.”

Rotblat and his students, Dr. Tal Levy and Dr. Khawla Alasad, began by considering that cells regulate their growth according to their available energy. When energy is plentiful, cells make fat and lots of proteins to store energy and grow. When energy is scarce, they must pump the brakes and stop making fat and proteins or burn themselves out. Tumors are mostly in a de-facto state of glucose starvation. So, they began thinking about locating the molecular brakes that enable the cancer cell’s survival in glucose starvation. If they could turn that off, then the tumor would die, but the regular cells, which are not glucose-starved, would remain unaffected.