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Scientists discover cancer treatment two-and-a-half times more effective when tumours have defective mitochondria

MedicalXpress Breaking News-and-Events Jan 31, 2024

Scientists have made an unusual discovery that could help to identify patients who are up to two-and-a-half times more likely to respond to currently available cancer drugs.

Scientists at the Cancer Research UK Scotland Institute and Memorial Sloan Kettering Cancer Center in the U.S. have "rewired" the DNA of mitochondria—energy factories found in every living cell. They found that creating mutations in parts of this DNA determines how well cancer will respond to immunotherapy—treatments that harness the body's natural defenses to attack cancer cells.

This discovery opens up new ways to identify patients who could benefit most from immunotherapy by testing for mitochondrial DNA mutations. Half of all cancers have mitochondrial DNA (mtDNA) mutations and this discovery shows for the first time that they could be exploited to improve cancer treatment.

In the future, combining treatments that mimic the effect of these mutations with immunotherapy could increase the chances of successful treatment for multiple types of cancer.

In a paper, titled "Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade in melanoma," in Nature Cancer the scientists demonstrate for the first time a direct link between mitochondrial DNA (mtDNA) mutations and response to cancer treatment. Surprisingly, they found that tumors with high levels of mtDNA mutations are up to two and a half times more likely to respond to treatment with an immunotherapy drug called nivolumab.

Nivolumab works by releasing a "brake" on the immune system to attack cancer cells. It is currently used to treat several different cancers, including melanoma, lung cancer, liver cancer and bowel cancer. The scientists believe that they could routinely test for mitochondrial DNA mutations in the future—enabling doctors to figure out which patients will benefit most from immunotherapy before starting treatment.

They also believe that mimicking the effects of the mitochondrial DNA mutations could make treatment-resistant cancers sensitive to immunotherapy—enabling thousands more cancer patients to benefit from this pioneering treatment.

The technology behind the discovery is now the subject of patents filed by Cancer Research Horizons, Cancer Research UK's innovation arm. It will help bring the technology to market to allow new treatments to be developed which disrupt the energy sources cancer uses to spread and grow. To date, Cancer Research Horizons has brought 11 new cancer drugs to market, which have been used in over six million courses of cancer treatment worldwide.

Group Leader at the Cancer Research UK Scotland Institute and the University of Glasgow and co-lead author of the study, Dr. Payam Gammage, said, "Cancer is a disease of our own bodies. Because cancer cells can look similar to healthy cells on the outside, getting our immune systems to recognize and destroy cancer cells is a complicated task.

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