Keto diet boosts pancreatic cancer drug effect: UCSF study

A recent study has found that a ketogenic diet can enhance the effectiveness of the cancer drug eFT508 by reducing the growth of pancreatic tumour, highlighting the crucial connection between dietary interventions and cancer therapies.

Scientists at the University of California, San Francisco (UCSF) have revealed a new approach to treating pancreatic cancer by demonstrating that a ketogenic diet can enhance the effectiveness of a cancer drug.

The research published in Nature shows that combining a high-fat ketogenic diet with the cancer drug eFT508 significantly hinders pancreatic tumour growth in laboratory mice. The success of this approach lies in the interaction between the diet, the drug, and cancer cell metabolism. 

Pancreatic cancer cells predominantly rely on fat as their primary energy source. The study found that eFT508, a drug currently in clinical trials, inhibits a protein called eukaryotic translation initiation factor 4E (eIF4E). 

This protein plays a crucial role in shifting the body’s metabolism towards fat burning, a process naturally triggered during fasting and when following a ketogenic diet. By blocking eIF4E and disrupting fat metabolism, the drug starves the cancer cells and limits their growth.

"Our findings reveal a new vulnerability in pancreatic cancer treatment," says Dr Davide Ruggero, professor at UCSF’s Departments of Urology and Cellular Molecular Pharmacology. "By adopting a diet that restricts the cancer cells' access to their main fuel source and pairing it with a targeted drug, we can precisely target and eliminate the cancer."

The study began with an investigation into the body's adaptation to fasting. The researchers observed that during fasting, the liver boosts the production of ketone bodies—alternative energy sources derived from fat. This process is regulated by eIF4E, which becomes more active during fasting or when on a ketogenic diet.

Building on this insight, the research team tested the combination of eFT508 and a ketogenic diet in animal models. The results showed that when the mice were placed on a ketogenic diet, the tumours, having adapted to fat as their energy source, were starved when eFT508 was introduced, leading to a substantial reduction in tumour growth.

Dr Haojun Yang, the study’s lead author, highlighted the broader implications of their findings. "Our study provides a biological explanation for the health benefits often associated with fasting and underscores how metabolic changes can be exploited to target cancer more effectively."
Dr Ruggero and Dr Kevan Shokat, a UCSF professor who co-developed eFT508, expressed optimism about the future applications of their work. "We've made a crucial connection between diet and cancer therapy." 
The approach could be adapted for other cancer types, suggesting that various diet-drug combinations might reveal further vulnerabilities in different cancers.