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 faulty in many types of cancer.
Specifically, these drugs target a cell signalling pathway called phosphatidylinositol-3 kinase (PI3K), which is activated by insulin.
Previous studies have shown that mutations in this kinase, or enzyme, are present in most tumours.
So, in an attempt to inhibit this pathway, over 50 drugs have been developed, with several clinical trials testing their efficacy.
Thus far, however, the results of these trials have been disappointing; for the most part, the drugs’ efficacy is hit-or-miss, or their toxicity is too high.
When the pancreas is unable to make up for the loss by producing more insulin, patients have to stop taking the drugs. Now, however, researchers led by Benjamin D. Hopkins, a postdoctoral associate at Weill Cornell Medicine in New York City, NY, may have found a way around this problem.
The ‘trendy’ ketogenic diet – a diet high in fats but very low in carbs – may be the best way to boost the efficacy of these new-generation therapies and avoid their side effects.
The researchers published their findings in the journal Nature.
Hopkins and colleagues examined the effect of a PI3K-inhibiting drug called buparlisib in a mouse model of pancreatic cancer.
“The rebound elevation in insulin is rescuing the tumour from death,” he goes on. So, to counter this effect, the researchers decided to try a few different blood sugar- and insulin-controlling drugs. They treated one group of mice with diabetes drugs, and another with a ketogenic diet.
‘A truly innovative approach to cancer’
“The ketogenic diet turned out to be the perfect approach,” says Hopkins. “It reduced glycogen stores, so the mice couldn’t release glucose in response to PI3K inhibition.”
Co-senior author Dr Siddhartha Mukherjee – an associate professor of medicine at the Columbia University Vagelos College of Physicians and Surgeons in New York City, New York – also weighs in on the findings.
“The fact that this drug itself was enabling a kind of resistance – at least in animal models – comes as a total surprise,” he adds. “We are excited to try this approach in humans.”
However, the authors caution that this is a combination approach, and that the keto diet on its own does not help to inhibit cancer but may even have the opposite effect.
Some mice fed a keto diet without also taking PIK3 inhibitors had faster-growing leukaemias, report the researchers.
“We have to make sure there is not some unanticipated toxicity,” Prof. Cantley says. “In any clinical trial for a drug that targets the PI3K enzyme, the patient should have their diet managed carefully.”
Source: Medical News Today