A new study finds that the ketogenic, popularly called keto diet helps to eliminate the side effects of a new generation of cancer drugs.
Scientists have been testing a new class of cancer drugs in recent years. They target a specific molecular pathway that has been shown to be out of order in many types of cancer. These drugs target a cell signaling pathway called phosphatidylinositol-3 kinase (PI3K), which is triggered by insulin.
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In an effort to prevent this pathway, over 50 drugs have been developed, with several clinical trials testing their effectiveness.
However, the results of these trials have been disappointing so far, for the most part, drugs toxicity of the drugs is too high.
Taking these drugs often leads to abnormally high levels of blood sugar (hyperglycemia). This occurs because impeding the pathway causes the insulin to drop, which upsurges the levels of blood sugar.
When the pancreas is finds it difficult to make up for the loss by producing more insulin, patients have to stop taking the drugs. However, a team of researchers led by Benjamin D. Hopkins, a postdoctoral associate at Weill Cornell Medicine in New York City, NY, may have found a way around this problem.
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Ketogenic diet which is currently trending, is a diet high in fats but very low in carbs. This diet may be the best way to boost the efficacy of these new-generation treatments for cancer and avoid their side effects.
Insulin affects the efficacy of cancer drugs
The researchers examined the effect of a PI3K-inhibiting drug called buparlisib in a mouse model of pancreatic cancer.
The model revealed that increasing insulin levels reactivates the PI3K pathway, thereby crushing the purpose of the cancer drug.
“Reactivating PI3K in the tumor makes the drug relatively ineffective,” explains corresponding study author Lewis C. Cantley, a professor of cancer biology in medicine at Weill Cornell Medicine.
“The rebound elevation in insulin is rescuing the tumor from death,” he goes on. So, to counter this effect, the researchers decided to try a few different blood sugar- and insulin-controlling drugs. They treated one group of mice with diabetes drugs, and another with a ketogenic diet.
The team discovered that of all the treatments tested, the keto diet performed best at both keeping blood sugar and insulin in check and at the same time hindering tumor growth signals.
“The ketogenic diet turned out to be the perfect approach,” says Hopkins. “It reduced glycogen stores, so the mice couldn’t release glucose in response to PI3K inhibition.”
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“This suggests that if you can block spikes in glucose and the subsequent insulin feedback, you can make the drugs much more effective at controlling cancer growth,” Hopkins stated.
Co-senior author Dr. Siddhartha Mukherjee — an associate professor of medicine at the Columbia University Vagelos College of Physicians and Surgeons in New York City, NY also contributed to the results of the research.
“This study represents a truly innovative approach to cancer. For decades, we’ve been trying to alter human metabolism to make cancer cells more sensitive to chemotherapy or targeted drugs,” Dr. Siddhartha Mukherjee stated.
He added that it came as a shock that the drug itself was enabling a kind of resistance in animal models.
“We are excited to try this approach in humans,” Murkhejee added.
However, the authors warned that this is a combination approach and that the keto diet on its own does not help to prevent cancer but may even have the opposite effect.
Some mice fed a keto diet without also taking PIK3 inhibitors had faster-growing leukemias, report the researchers.
In the future, the scientists wish to take the combination therapy to human clinical trials for treating blood cancer, breast cancer, and endometrial cancer.
The researchers published their findings in the journal Nature.