In a new study, scientists at the University of California, San Francisco (UCSF) have found that combining a high-fat ketogenic diet with a targeted cancer drug can eliminate pancreatic cancer in mice. The research, published in the prestigious journal Nature, offers fresh hope for one of the deadliest forms of cancer, which has long been resistant to treatment.

What is a Ketogenic diet?

A ketogenic diet is a high-fat, low-carbohydrate eating plan that shifts the body’s main energy source from carbohydrates to fats. By drastically reducing carbohydrate intake-typically to less than 50 grams per day-the body runs out of glucose, its usual fuel, and instead begins to break down fats into molecules called ketone bodies. This metabolic state, known as ketosis, allows the body and brain to use ketones for energy instead of glucose.

Originally developed as a medical therapy for difficult-to-control epilepsy, particularly in children, the ketogenic diet has also gained popularity for weight loss and is being studied for its potential benefits in conditions like diabetes, cancer, and neurological disorders. The diet usually consists of about 70-75% of calories from fat, 20-25% from protein, and only 5-10% from carbohydrates, requiring the exclusion of most grains, sugars, fruits, and starchy vegetables in favour of foods like meat, eggs, cheese, nuts, and healthy oils.

Effects of the Ketogenic Diet on Pancreatic Cancer Cells

While the ketogenic diet has been popular for weight loss, researchers have now discovered that it can also change the way cancer cells use energy. Pancreatic cancer cells, when deprived of their usual sugar supply, become dependent on fat-derived molecules called ketone bodies.

The UCSF team, led by Dr Davide Ruggero, found that these cancer cells adapt to the ketogenic diet by switching on certain genes that allow them to survive on ketones. However, this adaptation creates a weakness. The researchers used an experimental drug called eFT508, which blocks a key molecular pathway known as MNK-eIF4E. This pathway is crucial for the cancer cells to make the proteins they need to use ketones for energy.

When the mice were given both the ketogenic diet and the drug, their tumours shrank dramatically and, in some cases, disappeared altogether. The combination therapy worked by cutting off all possible energy sources for the cancer cells, effectively starving them to death. On its own, the drug had little effect, and the diet alone was not enough to stop the cancer. But together, they created a powerful “metabolic trap”.

The study also revealed that this approach triggered a special type of cell death called ferroptosis, which is caused by a build-up of iron and fat-based molecules inside the cancer cells. This further helped to destroy the tumours.

Experts say the findings could lead to new treatments for pancreatic cancer, which is notoriously difficult to cure and has a very low survival rate. The drug eFT508 is already being tested in clinical trials, raising hopes that this combined approach could soon be tried in human patients.

Researchers caution that more studies are needed to see if the same results can be achieved in people. However, the discovery highlights the potential of using diet alongside targeted therapies to outsmart cancer. It also opens the door to exploring similar strategies for other hard-to-treat cancers.

For now, the research offers a ray of hope for patients and families affected by pancreatic cancer, and marks an exciting step forward in the fight against this devastating disease.