How Ketogenic diet improves the efficiency of targeted cancer therapy

In a breakthrough study, the researchers from Weill Cornell Medicine Columbia University Irving Medical Center and NewYork-Presbyterian has found that the Ketogenic diet improves the efficiency of a class of cancer drug. Interestingly the drug was found to be ineffective in earlier clinical trials. The impetus for the current research stemmed from the repeated failure of the cancer drug targetting Phosphatidylinositol-3 kinase (PI3K) in human clinical trials. By the way, PI3K is involved in the regulation of various cellular processes that include growth, proliferation, differentiation and so on which in turn are involved in cancer.

For the majority of the drugs aimed at cancer control, PI3K has been the core target owing to the mutations in the pathway that regulate PI3K. So, the scientists

are of the view that by controlling/turning off the PI3K pathway, that promotes the growth of cancer cells, can induce effective treatment of cancer. However, patients who are taking these drugs developed high levels of blood sugar or hyperglycemia. However, the pancreas compensates by producing insulin to control blood sugar levels. But in some patients, blood glucose levels do not return to normal unless they stop taking the drugs.

What does the study reveal?

In the current study, the team of scientists found that rising insulin levels in response to hyperglycemia reactivated the pathway when treated with PI3K inhibitor Buparlisib. The team then turned their attention towards two drugs metformin and sodium-glucose cotransporter 2 inhibitors or simply ketogenic diet. Out of this metformin did not control tumour growth, while on the other hand, SGL2 inhibitors effectively prevented the reabsorption of glucose in kidneys and eliminated via urine. So, this a way prevented the spike in glucose levels and in turn insulin feedback. So, the approach proved to be effective in the control of cancer growth.

Here the interesting aspect is that Ketogenic diet alone has no impact when it is tried independently. And in some cases like leukaemia, it even enhanced the tumour growth. But when Ketogenic diet has been adopted along with PI3K inhibitors, it effectively controlled the tumour growth.

Future Research

Although the current research has been carried out in mouse models, the team is confident of replicating the results in the human trials. Further, they are now planning to test the FDA approved drug with the Ketogenic diet specially designed by nutritionists. They will study the outcome of the approach in patients suffering from leukaemias or lymphomas, breast cancer and endometrial cancer.

The Research study is published in the Journal Nature

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