Researchers at the University of Notre Dame have discovered that adding a pre-ketone supplement, related to the ketogenic diet, significantly improves the effectiveness of a type of cancer therapy in treating prostate cancer.
The findings, led by Xin Lu, the John M. and Mary Jo Boler Collegiate Associate Professor in the Department of Biological Sciences, were recently published in the journal Cancer Research.
Prostate cancer, which is the most common cancer among American men, has shown resistance to a form of treatment known as immune checkpoint blockade (ICB) therapy.
This therapy typically works by stopping certain proteins from interacting, thereby allowing the body’s T cells, or fighter cells, to attack the cancer. However, this has not been very effective against prostate cancer.
Sean Murphy, a doctoral student in Lu’s lab and a key author of the study, inspired by his own adherence to a ketogenic diet, proposed that a supplement mimicking this diet might help overcome the resistance seen in prostate cancer treatments.
The ketogenic diet, which is high in fats and low in carbohydrates, forces the body to use fats for energy instead of sugars, and this principle guided their experiments.
The research team conducted their study using mouse models, dividing them into groups to receive different treatments: some received immunotherapy alone, others were put on a ketogenic diet, some were given a pre-ketone supplement, and others received combinations of these treatments.
The most significant results came from the combination of the pre-ketone supplement and immunotherapy. This duo not only reduced the size of the tumors but also extended the life spans of the mice.
Remarkably, 23 percent of the mice treated with this combination were completely cured, showing no signs of tumors.
The study suggests that ketones disrupt the energy processes of cancer cells and enhance the body’s immune response against them.
The researchers emphasized that the key factor was not the reduction of carbohydrates but the presence of ketones that interfered with the cancer cells’ survival.
Beyond just treating cancer, the research indicated that the main ketone body used in the supplement also played a role in decreasing the number of neutrophils in the tumor environment.
Neutrophils usually hinder T cells from fighting cancer effectively, but with their reduction, T cells could perform better.
The team used advanced techniques like single-cell RNA sequencing to delve deeper into the cellular changes within the tumors, confirming that the combination of the supplement and the therapy reprogrammed the immune response directly within the tumors.
This breakthrough not only paves the way for potential new cancer treatments but also opens up possibilities for investigating the effects of ketogenic diets and ketone supplements on other diseases characterized by immune dysregulation, such as inflammatory bowel disease and arthritis.
With a strong team of researchers from the University of Notre Dame, including Sharif Rahmy, Dailin Gan, and others, the study underscores a significant advance in understanding and potentially combating prostate cancer through dietary-based strategies.
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The research findings can be found in Cancer Research.
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