A study conducted by researchers from the University of Notre Dame investigated the potential of combining a pre-ketone supplement with immunotherapy to treat prostate cancer in a mouse model. Prostate cancer affects about 13% of cisgender men globally, making it the second most frequently diagnosed cancer. Despite advancements in screening and early detection, more advanced stages of the disease can be challenging to treat, with about one in 44 men dying from prostate cancer. Immunotherapy, which utilizes the body’s immune system to combat cancer, has shown promise in treating various cancer types. However, advanced prostate cancer has been resistant to this treatment due to factors such as an increase in pro-tumor immune cells and insufficient tumor-specific antigens for the immune system to target.

The researchers explored the use of a pre-ketone supplement in combination with immunotherapy to sensitize prostate cancer to the treatment. This supplement, derived from the keto diet, contains beta-hydroxybutyrate (BHB), which has properties similar to HDAC inhibitors known to sensitize prostate cancer models to immunotherapy. The researchers aimed to determine if the presence of BHB in the pre-ketone supplement could enhance the response to immunotherapy in the mouse models. The study involved dividing the mice into six groups, with three groups receiving only immunotherapy, a keto diet, or a pre-ketone supplement, while two groups received a combination of the diet or supplement with immunotherapy. The results showed that the combination of the pre-ketone supplement and immunotherapy yielded the best outcomes, with 23% of the mice becoming tumor-free.

According to the researchers, the pre-ketone supplement enhances immunotherapy in two ways. Firstly, it makes cancer cells more detectable to the immune system by increasing the presentation of molecular features on the surface of cancer cells. Secondly, the ketone body from the supplement, combined with immunotherapy, elicits special metabolic and molecular effects on immune cells, stimulating them to attack the cancer cells. The researchers expressed optimism about the 23% cure rate seen in the mouse models but acknowledged the need to optimize the combination further and explore additional therapies to increase success rates. While the results are promising, it is important to note that the study is at a preclinical stage, and more research is needed to validate the findings in clinical trials and potentially expand the approach to other cancer types.

Medical oncologist Wael Harb, who was not involved in the study, found the idea of combining a ketogenic diet or ketone supplement with immunotherapy for prostate cancer treatment intriguing. While immunotherapy has shown success in other cancer types, prostate cancer has been resistant to traditional therapies. Harb emphasized the necessity of moving from animal models to human clinical trials to establish the efficacy and safety of the combination treatment. He highlighted the importance of carefully monitoring weight loss in cancer patients following a ketogenic diet, as weight loss can be detrimental for individuals undergoing cancer treatment. Harb recommended further research to determine the optimal level of ketosis required and to explore the applicability of the approach to other tumor types.

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