A Ketogenic Diet Could Improve the Response to Pancreatic Cancer Therapy

A study of fasting and the ketogenic diet reveals a new vulnerability of pancreatic tumors to an existing cancer drug.

By Levi Gadye | UCSF.edu | August 14, 2024

Foods for ketogenic diets, which include high-fat foods like salmon, avocado, eggs, nuts, broccoli, asparagus, and cheese.

Scientists at UC San Francisco have discovered a way to get rid of pancreatic cancer in mice by putting them on a high fat, or ketogenic, diet and giving them cancer therapy.

The cancer therapy blocks fat metabolism, which is the cancer’s only source of fuel for as long as the mice remain on the ketogenic diet, and the tumors stop growing.

“This is the foundation for a new way to treat cancer with diet and personalized therapies.”

Davide Ruggero, PhD

The team made the discovery, which appears August 14 in Nature, while they were trying to figure out how the body manages to subsist on fat while fasting.

“Our findings led us straight to the biology of one of the deadliest cancers, pancreatic cancer,” said Davide Ruggero, PhD, Goldberg-Benioff Endowed Professor and American Cancer Society Research Professor in the Departments of Urology and Cellular Molecular Pharmacology at UCSF and senior author of the paper.

Ruggero’s team first uncovered how a protein known as eukaryotic translation initiation factor (eIF4E) changes the body’s metabolism to switch to fat consumption during fasting. The same switch also occurs, thanks to eIF4E, when an animal is on a ketogenic diet.

They found that a new cancer drug called eFT508, currently in clinical trials, blocks eIF4E and the ketogenic pathway, preventing the body from metabolizing fat. When the scientists combined the drug with a ketogenic diet in an animal model of pancreatic cancer, the cancer cells starved.

“Our findings open a point of vulnerability that we can treat with a clinical inhibitor that we already know is safe in humans,” Ruggero said. “We now have firm evidence of one way in which diet might be used alongside pre-existing cancer therapies to precisely eliminate a cancer.”

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