In a recent study published in the journal Nature, scientists from the Weill Cornell School of Medicine in the United States, Columbia University Medical Center and other institutions confirmed that experiments in mice showed ketones composed of low-carbohydrate, high-fat A ketogenic diet can improve the efficacy of a new cancer drug.
In a paper on July 4th entitled 'Suppression of insulin feedback enhances the efficacy of PI3K inhibitors', the team led by Dr. Lewis C. Cantley asked 'Why to target the insulin-activated enzyme PI3K (phosphatidylinositol-3 kinase, The PI3K mutation is associated with a variety of cancers. The anticancer drugs did not achieve the expected results'. A possible explanation is given. At the same time, the study proposes a feasible strategy that is expected to improve the anticancer potential of such therapies.
R&D dilemma targeting PI3K
The PI3K mutation frequently makes this gene an attractive target for anticancer drugs. Currently, more than 20 therapies that inhibit PI3K enzymes have entered clinical trials, but so far the results have been disappointing. The patient's blood sugar level becomes too high, or suffers from hyperglycemia. However, this condition is usually temporary because the patient's pancreas can lower blood sugar by producing more insulin, but some patients cannot have blood sugar. Going back to normal level, therefore, have to stop taking the medicine.
Dr. Benjamin D. Hopkins, the first author of the paper, said: 'In theory, if we turn off the PI3K pathway that promotes cancer cell growth, we should be able to see the patient's clinical response to these drugs, but the results are not as we expected.'
Increased insulin levels
So, where is the problem? In this study, Dr. Hopkins et al found that elevated insulin levels reactivated PI3K in mice bearing pancreatic tumors treated with the PI3K inhibitor Buparlisib.
The authors say that it is the rise in insulin that rescues tumors from death. Reactivation of PI3K in tumors makes PI3K inhibitors relatively ineffective.
Ketone diet 'best performing'
After obtaining the above findings, scientists hope to find a way to help control blood sugar and insulin levels. In the next experiment, in addition to PI3K inhibitors, they also added diabetes drugs metformin or SGLT2 inhibitors or ketogenic diet pairs. The mice are treated.
The results showed that: 1) Metformin, which increases insulin sensitivity, does not have much effect on glucose or insulin peaks or cell signals that promote tumor growth; 2) SGLT2 inhibitors that prevent glucose reabsorption in the kidneys reduce glucose and insulin Peak and tumor growth signals; 3) Used to control insulin levels, the ketogenic diet that has been clinically applied for about 40 years has done the best in preventing glucose and insulin surges and inhibiting tumor growth signals.
The ketogenic diet proved to be the perfect method. It reduced the storage of glycogen, so mice could not release glucose in response to PI3K inhibitors. This suggests that PI3K inhibition can be prevented if glucose amplification and subsequent insulin feedback are prevented. The agent is more effective in controlling cancer growth,' Dr. Hopkins explained.
However, Dr. Hopkins warns that the ketogenic diet alone does not necessarily help control cancer growth, and in some cases it may even be harmful. In the study, when scientists investigated the lack of PI3K inhibitors When the ketogenic diet was affected in a variety of cancer mice, they found that the ketogenic diet had little effect on the tumor and caused some leukemias to develop faster.
Next plan
Dr. Cantley said that any drug that targets PI3K may be ineffective unless the patient is able to maintain low blood sugar levels through diet or medication. Next, they want to investigate whether to combine FDA-approved intravenous PI3K inhibitors with a ketogenic diet (by nutrition) Specially prepared by theologist) is safe for patients with breast cancer, endometrial cancer, leukemia or lymphoma and can improve treatment outcomes.
'This research represents a truly innovative cancer therapy. For decades, we have been trying to change human metabolism, making cancer cells more sensitive to chemotherapy or targeted drugs. We are trying this therapeutic approach in humans. I am very excited. ' The author of the paper co-author, Dr. Siddhartha Mukherjee, concluded.
