New Brain Tumor Insight Could Help Several Cancers

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A major cancer milestone – the kind that makes the evening news – doesn’t happen in a eureka moment. It’s the product of years of research at the molecular level. It could be decades before enough evidence emerges to lead to new therapies, which then go through rigorous testing until they get approval for use in cancer patients. Often, these types of early discoveries don’t hit the radar of the everyday person, but they are crucial pieces in the enormous and complex cancer puzzle.

Brain cancer is one area of the puzzle that needs urgent attention. Glioblastoma multiforme, the most common and lethal type of brain cancer, has a five-year survival rate of just 4% for adults ages 55-64. The good news is that American Cancer Society grantees are making important, promising strides in understanding malignant brain tumors.

One such grantee is Deliang Guo, PhD, an assistant professor at The James, The Ohio State University Comprehensive Cancer Center. Guo was the lead researcher on a recent study that discovered a cellular mechanism that could lead to new therapies for glioblastoma and potentially other cancers.

The mechanism involves a molecular pathway and a protein called SREBP, which plays a role in how your cells process (or metabolize) sugar and fat. Guo and colleagues found out that blocking this pathway slowed glioblastoma tumor growth, according to the findings published in November in the journal Cancer Cell.

“Metabolic reprogramming is emerging as a new hallmark of cancer research. Understanding how tumor cells regulate metabolism provides a promising opportunity to treat cancer,” says Guo. “I believe that SREBP-1 is a very promising therapeutic target in cancer.”

To explain the science in simple terms: Glucose provides fuel for cells, enabling them to divide and form new cells. (This happens at a rapid rate in cancer cells.) For a new cell to form, it needs a membrane – think of it like an outer shell protecting the cell. The creation of cell membranes requires lipids (fats).

By interfering with the SREBP pathway in glucose metabolism, lipid metabolism was impaired. Without enough lipids, cancer cells couldn’t continue to rapidly divide because they didn’t have the materials to make new membranes.

“Providing an explanation for how glucose is connected to lipid metabolism and membrane formation is exciting. It points the way toward new strategies for blocking tumor growth and potentially metastasis,” says Charles Saxe, PhD, director of the cancer cell biology and metastasis program at the American Cancer Society. “Though this study focused on glioblastoma, the principles uncovered are likely to be general, meaning they could apply to other types of cancer.”

The discovery was made in mice, so there is still a long way to go until this new understanding becomes part of the foundation for new therapies. Guo will continue to focus his research in this specific area, just as he has since 2007, when he was a researcher at UCLA and first discovered the need for more study on the link between glucose and lipid metabolism. “In the next step, we endeavor to explore the therapeutic potential for SREBP-1 in glioblastoma and other malignancies,” Guo says.

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