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

A new study has revealed a surprising link between mitochondrial DNA mutations and response to immunotherapy, a type of cancer treatment that harnesses the body’s natural defenses to attack cancer cells.

Mitochondria are the energy factories of the cell, and they have their DNA, which is separate from the nuclear DNA. Mutations in mitochondrial DNA (mtDNA) are common in cancer, affecting about half of all tumors. However, the role of these mutations in cancer development and treatment has been unclear.

The study, led by researchers at the Cancer Research UK Scotland Institute and Memorial Sloan Kettering Cancer Center in the U.S., used a novel technique to “rewire” the mtDNA of cancer cells, creating different types of mutations. They then tested how these mutations affected the response to nivolumab, an immunotherapy drug that is used to treat several cancers, including melanoma, lung cancer, liver cancer, and bowel cancer.

The researchers found that tumors with high levels of mtDNA mutations were up to two and a half times more likely to respond to nivolumab than tumors with low levels of mutations. They also found that the type of mutation mattered: mutations that disrupted the function of the mitochondria, making them less efficient at producing energy, were associated with better responses than mutations that did not affect the function.

The researchers believe that the mtDNA mutations make the cancer cells more vulnerable to immunotherapy by altering their metabolism and increasing the production of molecules that attract the immune system. They also suggest that testing for mtDNA mutations could help identify patients who are more likely to benefit from immunotherapy and that mimicking the effects of the mutations could enhance the effectiveness of immunotherapy for other patients.

The study, published in Nature Cancer, is the first to demonstrate a direct link between mtDNA mutations and response to cancer treatment. It opens up new avenues for exploiting the mitochondrial vulnerabilities of cancer cells to improve cancer therapy.

The study was funded by Cancer Research UK, the Medical Research Council, the Wellcome Trust, the European Research Council, the National Institutes of Health, the Ludwig Institute for Cancer Research, and the Parker Institute for Cancer Immunotherapy.