A new study in mice reveals that the ketogenic or keto diet helps eliminate the side effects of new generation cancer drugs.
In recent years, scientists have been testing a new class of cancer drugs. They target a specific molecular pathway that has been shown to be defective in many types of cancer.
Specifically, these drugs target a cell signaling pathway called phosphatidylinositol-3 kinase (PI3K), which is activated by insulin. Previous studies have shown that mutations in this kinase or enzyme are found in most tumors.
So, in an attempt to block this pathway, more than 50 drugs have been developed and many clinical trials have been conducted to test their effectiveness. But so far, the results of these trials are disappointing; Often, the effectiveness of the drugs is ineffective or their toxicity is very high.
Taking these medications often leads to hyperglycemia, or abnormally high blood sugar. This is because inhibiting the pathway causes insulin to drop, which increases blood sugar levels.
When the pancreas cannot compensate for the loss by producing more insulin, patients must stop taking the medications. But now, researchers led by Benjamin D. Hopkins, a postdoctoral fellow at Weill Cornell Medicine in New York City, NY, may have found a way around this problem.
The "trendy" ketogenic diet—from fats a diet high but very low in carbohydrates – this may be the best way to increase the effectiveness of new generation treatments and avoid their side effects. The researchers published their findings in Nature. They examined it. The model revealed that increased insulin levels reactivate the PI3K pathway, defeating the purpose of the cancer drug. "It makes it relatively ineffective," he explains.
"The rebound rise in insulin saves the tumor from death," he continues. this ned So, the researchers decided to try several different blood sugar and insulin controlling drugs. They treated one group of mice with diabetes drugs and the other with a ketogenic diet.
'A truly innovative approach to cancer'
Of all the treatments tested, the keto diet had both It performed best at keeping both blood sugar and insulin in check while simultaneously inhibiting tumor growth signals.
"The ketogenic diet turned out to be an excellent approach," Hopkins says. "It reduced glycogen stores, so mice could release glucose in response to PI3K inhibition." “This means,” says senior author Dr. Siddhartha Mukherjee – professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York, NY – also weighs in on the findings. "This work represents a truly innovative approach to cancer. For decades, we have been trying to modify human metabolism to make cancer cells more sensitive to chemotherapy or targeted drugs."
-Siddhartha Mukherjee
< “The fact that this drug itself enables some form of resistance – at least in animal models – comes as a complete surprise,” he adds. “We are excited to try this approach in humans.”However, the authors point out that this is a combination approach and that the keto diet by itself does not help prevent cancer, but may have the opposite effect. Some mice fed a keto diet without taking PIK3 inhibitors had faster-growing leukemias, researchers reported.
In the future, scientists want to take the combination therapy to human clinical trials to treat breast cancer, endometrial cancer and blood cancer. “We have to make sure there is no unexpected toxicity,” Cantley says. "In any clinical trial for a drug targeting the PI3K enzyme, the patient's diet needs to be carefully managed."
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