Scientists have discovered that mutations in mitochondrial DNA can predict a patient’s response to immunotherapy, which could lead to more personalized and effective cancer treatments. Credit: SciTechDaily.com
An in-depth study shows that mitochondrial DNA Mutations are key indicators of a patient’s likelihood of responding to immunotherapy, changing cancer treatment approaches.
Scientists funded by Cancer Research UK have made a rare discovery that could help identify patients who are up to two and a half times more likely to respond to existing cancer drugs.
Scientists from the UK’s Scottish Institute of Cancer Research and the US-based Memorial Sloan Kettering Cancer Center have “re-engineered” the DNA of mitochondria – the energy factories in every living cell. They found that mutations in this DNA segment determine how well cancer responds to immunotherapy — treatments that use the body’s natural defenses to attack cancer cells.
This discovery opens new avenues to identify patients who may benefit most from immunosuppressive therapy 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 used to improve cancer treatment.
In the future, combining therapies that mimic the effects of these mutations with mutation therapy will increase the chance of successful treatment for many types of cancer.
In a paper published in the journal Natural cancer Today (January 29)Th), scientists have shown for the first time a direct link between mitochondrial DNA (mtDNA) mutations and response to cancer treatment. They found that tumors with a surprisingly high number of mtDNA mutations were up to two and a half times more likely to respond to treatment with the immunosuppressive drug nivolumab.
Nivolumab works by releasing the “brakes” on the immune system to attack cancer cells. It is currently used to treat a variety of cancers, including melanoma, lung cancer, liver cancer, and colon cancer. The scientists believe that in the future, mitochondrial DNA mutations could be routinely tested for – allowing doctors to determine which patients would benefit most from immunosuppressive therapy before starting treatment.
In addition, mimicking the effects of mitochondrial DNA mutations could make treatment-resistant cancers more susceptible to immunotherapy – allowing thousands more cancer patients to benefit from this pioneering treatment.
The technology behind the discovery is now the subject of a patent filed by Cancer Research Horizons, Cancer Research UK’s innovation arm. It helps bring the technology to market to develop new treatments that disrupt the energy sources that cancer uses to spread and grow. To date, Cancer Research Horizons has brought 11 new anticancer drugs to market, which have been used in more than six million cancer treatments worldwide.
Group Leader at Cancer Research UK Scotland Institute and University of Glasgow And the study’s lead author, Dr. Payam Gammage, said:
“Cancer is a disease of our body. Cancer cells can mimic healthy cells on the outside, so getting our immune system to recognize and destroy cancer cells is a complex task.
“More than half of cancers have mutations in mitochondrial DNA. But when we created these mutations in the lab, we found that tumors with the most mutated mitochondrial DNA were the most sensitive to the mutation.”
“Thanks to this research, we now have a powerful tool that gives us a completely new approach to stopping cancer in its tracks.”
Dr. Ed Reznick, assistant professor of computational oncology at Memorial Sloan Kettering Cancer Center and lead author of the study, said:
“Mitochondrial DNA has been a mystery for decades. Each cell has thousands of copies and until now it has been very challenging to study how mtDNA mutations affect cancer by consistently engineering mutations.
“For the first time, when we create mitochondrial DNA mutations in the lab, we can see exactly what they do. But what surprises us is how much the cells around the tumor are affected – which we can use to make the tumor more susceptible to treatment.”
“This research opens up a world where we can re-use the tumor’s energy sources and work to beat cancer faster.”
Dr Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK and Chief Executive of Cancer Research Horizons, said:
“After years of painstaking laboratory research funded by Cancer Research UK, we have identified a very weak point in cancer. Mitochondrial DNA mutations are a common part of cancer and this exciting discovery has limitless potential.”
“Treatments that use overloaded mitochondria in cancer are now possible. Now we need clinical trials to see which compounds work best in patients. With our innovation engine in cancer research horizons, we plan to accelerate this discovery into the clinic and benefit as many patients as possible.
The paper will be published today (January 29).Th) in Natural cancer.
Reference: “Mitochondrial DNA mutation induces aerobic glycolysis to enhance checkpoint blockade in melanoma” 29 Jan 2024; Natural cancer.
DOI: 10.1038/s43018-023-00721-w