Researchers at The University of Texas MD Anderson Cancer Center have discovered a new approach that can significantly enhance the anti-tumor response in preclinical models of one of the most aggressive and difficult-to-treat cancers—pancreatic cancer.

The study, the findings of which were published in the journal Cancer Research, showed that inhibition of a specific mitochondrial enzyme, GFER, combined with immune checkpoint blockade, can lead to a powerful anti-tumor response in animal models.

Pancreatic cancer is known for its aggressiveness and its ability to create an immunosuppressive environment around itself, and this interferes with the effectiveness of many therapies, including immunotherapy.

The aforesaid researchers found that the GFER enzyme plays an important role in shaping this environment precisely through altering tumor cell metabolism at the mitochondrial level. When GFER is active, it weakens immune cell function and contributes to tumor resistance to treatment.

In their study, the researchers conducted genomic screening, and identified GFER and several other genes associated with mitochondrial metabolism as critically important for the growth of pancreatic tumor cells. They then demonstrated that inhibition of GFER suppresses oxidative phosphorylation, disrupts the cell cycle, blocks energy sources, and induces stress that interferes with tumor growth in preclinical models. Moreover, this approach activates immune cells, making tumors more responsive to therapy by using immune checkpoint inhibitors.

According to the study’s lead author, these findings underscore the importance of targeting mitochondrial processes as a key mechanism shaping the immunosuppressive environment in pancreatic tumors.

Combining GFER inhibition with immunotherapy could become a promising strategy for treating patients whose tumors were previously resistant to existing methods.

However, additional clinical trials are needed to confirm the effectiveness of this approach in humans.