Popular keto diet set to be tested in humans to see if it can amp up effect of weak PI3K drugs

Could a popular diet be put on the menu of treatment options for some cancer patients? A new mouse study suggests that the answer might be yes — and a marquee scientist in the field is set to test it in humans.

Combining a ketogenic diet with PI3K inhibitors like Zydelig (Gilead) and Aliqopa (from Bayer) appears to be an effective way to combat the interference of an insulin response mechanism triggered when the drug interrupts insulin production and then sets off an alternative spike in insulin production which may well be responsible for either reducing or eliminating its efficacy.

Feeding mice a ketogenic diet — with high fat, adequate protein and extremely low carbs — was able to lower blood glucose, overcoming the treatment loop, according to the study published in Nature. An SGLT2 drug that blocked absorption of glucose in the kidneys also had the same effect.

Siddhartha Mukherjee

Now oncologist Siddhartha Mukherjee — of The Emperor of all Maladies fame — is setting up a 40-patient study with Bayer to see how this works in humans.

“If you combine them with a diet which [keeps insulin low], all of a sudden these drugs become effective,” Mukherjee told The Guardian. “The diet really works like a drug.”

A new approach to boost the efficacy of PI3K could have a positive impact here. Researchers have seen poor or weak survival advantages with these drugs, which spurred Roche to dump taselisib a few weeks ago at the end of Phase III.

Gilead’s pioneering Zydelig got slapped with a black box warning on side effects, forcing an end to its quest to complete frontline trials. Bayer’s Aliqopa (copanlisib) was approved last fall for follicular lymphoma patients on the basis of some promising results, crowding a field that Verastem hopes to join with duvelisib, a PI3K dropped by Infinity Pharmaceuticals after AbbVie walked away after getting a glimpse of unimpressive — but still approvable — results.

The ketogenic diet is simple enough. You slash your carbs to a limit of 20 grams a day, forcing the body to switch to the fat you’re pumping in as an alternative energy source. It’s a proven method for fast weight loss, with most pros in the diet arena warning that few adults can sustain it. Cancer researchers have also studied keto to see if starving tumors — such as glioblastoma — of carbs can shut off a key energy source.

So here come the caveats.

First, mice aren’t humans. 

The researchers here also aren’t claiming that cancer patients should dropkick carbs in response to what they’ve found. For one thing, there still is precious little hard evidence that a keto diet alone could significantly help cancer patients. And in some cases clinicians suspect the approach could be counter productive.

Professor Karen Vousden, Cancer Research UK’s chief scientist, had this cautionary note to add to The Guardian about diet and cancer: “There’s a lot of black magic and old wives’ tales. None of it is really based on any evidence.”

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
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