P.Sick containers often include warnings about specific foods or drinks that should be avoided while taking certain medications. For example, grapefruit the juice interferes with the breakdown of statins in the intestines, causing the drug to remain active in the body for too long.¹ Likewise, consume alcohol Taking medications can be dangerous because it can alter the hepatic metabolism of the drug, leading to additional or exaggerated side effects and possible liver damage due to overloading the overall metabolic functioning of the body.²

However, not all diet-drug interactions are bad. In a recent study, Davide Ruggerocancer biologist at the University of California, San Francisco, and his team found that a high-fat, low-carb diet, known as the ketogenic, or keto, diet, could reshape the translatome, or entire molecules that are actively translated, fat-loving pancreatic cancer cells in mice. These modifications improved the effectiveness of targeted cancer therapy to suppress tumor growth. The results, published in Naturelay the groundwork for researchers to study personalized combinations of drugs and diets as potential cancer therapies.³

“We live in a time where these different diets – intermittent fasting, ketogenic diet, calorie restriction – are increasingly used for metabolic diseases like diabetes, but the focus has been on using these diets when we think of cancer patients,” Ruggero said.

Previously, Ruggero found that mice fasted or on a ketogenic diet had increased phosphorylation of a protein called eukaryotic translation initiation factor (eIF4E)which helps the liver metabolize lipids.⁴ In their recent study, the team wanted to uncover the metabolic mechanisms underlying this beneficial effect and explore how the ketogenesis pathway could be used to boost cancer treatment.

First, the team characterized the relationship between high fat and eIF4E by measuring their activity in the liver. Their experiments showed that a ketogenic diet increases fatty acids in the liver, triggering ketogenesis by activating a pathway that begins with the phosphorylation of eIF4E. Increased eIF4E phosphorylation altered translational control in liver cells, thereby increasing the expression of genes involved in fat metabolism. This triggered a metabolic shift toward burning fat for energy instead of the typical glucose. Burning fat in turn produces ketone bodies in the animals’ blood, characteristic of a ketogenic diet.

We already knew that pancreatic cancer, one of the deadliest cancers, could use ketone bodies for an energy sourceas an alternative to typical glucose.^3.5 So, Ruggero and his team wondered if they could make pancreatic cancer cells dependent on this eIF4E-initiated energy pathway by simply changing the animals’ diet.

Ruggero’s team used a mouse model of pancreatic cancer to test the effects of tomivosertib, a drug that inhibits phosphorylated eIF4E, in combination with a ketogenic diet. With their only food source pharmacologically cut off, the cancer cells starved to death and tumor growth was blocked. However, the compound had no effect on mice fed a normal diet.

“It was an incredible result,” Ruggero said. “Cancer is not cells from the universe or Mars or whatever, it’s a process that actually hijacks something that was already happening (in our bodies) for other reasons.”

“The buzzword now is ‘diet-drug interactions,’” said Michael Pollakoncologist and researcher at McGill University who was not involved in the study. “If we had an anti-cancer diet, make no mistake, this would be my first choice,” Pollak said. Unfortunately, Pollak noted, that’s not where the scientific evidence points. He explained: “Diet changes by themselves may not have enough of an impact to make a difference, but they may actually sensitize tumors to certain medications. »

Preclinical cancer studies in mice have shown promise for keto diets.⁶ However, human trials in this area were difficult to interpretpartly because the methods vary widelyand the ideal combinations of foods for different types of cancer are not yet known, preventing the field from draw solid conclusions.^7-9

Ruggero and his team next want to explore how and why different types of cancer respond more or less to different types of diets and therapies in order to contribute to the development of effective personalized medicines. Ruggero said: “We always think about personalized medicine from just the pharmacology perspective. What’s interesting here is the idea that if we can think of personalized medicine based on what you want to eat and what you can eat, it allows the patient… (to) induce a self-induced treatment that can help the medicine work. better. It’s very cool to think about personalized medicine based on food.