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Tuesday 12 November 2019

Ketogenic diet could be the key to making a cancer treatment work

PI3K inhibiting drugs have shown little success. Now researchers may have figured out why.

4th July 2018

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A ketogenic diet is low carbs and high in fat. This can help keep insulin levels low, which is believed to improve the effectiveness of certain cancer drugs. 

For their study, scientists tested the drugs in mice who’d been fed either a standard or ketogenic diet. While it was largely ineffective for the mice eating standard fare, the treatment shrunk the tumors of mice who’d eaten the ketogenic diet.

The drugs in question work by inhibiting the PI3K pathway, a cell-signaling network that’s overactive in many types of cancer. However, while there are lots of PI3K inhibitors in development, researchers and pharmaceutical companies have struggled to make them effective. “While more than 20 PI3K inhibitors have entered cancer clinical trials, only two have been approved,” said Benjamin Hopkins, a postdoctoral medical researcher at Cornell University who is one of the study’s authors.

The researchers posited that insulin may be the reason these drugs aren’t living up to their promise. The PI3K enzyme regulates glucose metabolism. 

When glucose levels are high, the body produces insulin. Insulin stimulates the PI3K pathway which then leads to cell proliferation and tumor growth. This means that rising insulin levels could counteract any drugs taken to inhibit the enzyme.

So the team started looking for ways to keep patients’ insulin low while they’re taking PI3K inhibiting drugs. 

They tested two approaches in mice: a diabetes medication and a ketogenic diet, which prevents glycogen from being stored in liver and muscle tissue. “Both interventions caused dramatic improvements in responses to multiple PI3K inhibitors in multiple cancer types,” said Hopkins.
The researchers stress that their study doesn’t suggest a ketogenic diet alone would help prevent or treat cancer. In a leukemia model, the ketogenic diet even seemed to make the cancer worse in mice who hadn’t received a PI3K inhibiting drug. 

“But the combination of a PI3K inhibitor and ketogenic diet was effective in a surprisingly wide spectrum of cancers,” said Hopkins. “Our study suggests that more patients would respond to these drugs if their serum insulin could be maintained at low levels during therapy by these interventions.”

To see if their approach will also work in humans, the study’s authors plan to conduct a clinical trial within a year. This could provide some of the answers researchers, drug developers, and patients are looking for. Hopkins explains: “Patients often ask whether they should change their eating habits when diagnosed with cancer, and physicians admit that there is little evidence that this can improve the outcome. Conducting a clinical trial to test this idea is critical.”

Featured image courtesy of jensteele via flickr
https://www.researchgate.net/blog/post/ketogenic-diet-could-be-the-key-to-making-a-cancer-treatment-work