Researchers at the University of California, San Francisco (UCSF) have discovered that the ketogenic diet can improve the response to treatment of lung cancer . The study, published this Wednesday (14) in the renowned scientific journal Nature, was carried out on mice, but may bring new insights into how diet can act in the treatment of the disease.
THE study showed that in mice that remained on the ketogenic diet, the cancer therapy was able to block the metabolism of fat—the cancer’s fuel source—and stop tumor growth. The discovery was made as researchers tried to figure out how the body manages to subsist on fat during fasting.
The ketogenic diet is characterized by low carbohydrate consumption, high intake of good fats and moderate protein intake. Foods allowed on this diet include meat, fish, seafood, eggs, nuts, olive oil and other natural sources of fat.
Ketogenic diet makes cells “starve”
The researchers first discovered that a protein known as eukaryotic translation initiation factor (eIF4E) alters the body’s metabolism to increase fat consumption during fasting. The same change also occurs when an animal is following a ketogenic diet, thanks to the action of the same protein.
They then discovered that a new cancer drug called eFT508 — which is currently undergoing clinical trials — blocks the protein and ketogenic pathway, preventing the body from metabolizing fat. However, when the researchers combined the drug with a ketogenic diet in mice with pancreatic cancer, the cancer cells starved to death.
“Our findings open up a vulnerability that we can address with a clinical inhibitor that we already know is safe in humans,” said Davide Ruggero, the Goldberg-Benioff Endowed Professor and American Cancer Society Research Professor in the Departments of Urology and Molecular Cellular Pharmacology at UCSF, and senior author of the study. press release.
“We now have firm evidence of a way in which diet can be used alongside pre-existing cancer therapies to precisely eliminate a cancer,” he adds.
How does fat metabolism work?
Humans can survive for weeks without food, in part because the body burns stored fat. This burning occurs during fasting, when the liver converts fat into ketone bodies to use in place of glucose, the body’s normal energy source.
The researchers found that the eIF4E protein in the liver became more active during fasting, suggesting that it is involved in the production of ketone bodies (ketogenesis). They also found that the protein was activated by the presence of free fatty acids, which are released from fat cells at the beginning of fasting to provide energy for the body.
“The metabolite that the body uses to produce energy is also being used as a signaling molecule during fasting,” Ruggero explains. “For a biochemist, seeing a metabolite act as a signal was the coolest thing,” he says.
How can the ketogenic diet reduce pancreatic tumor, according to the study?
These changes in the liver—production of ketone bodies from burning fat, along with an increase in eIF4E activity—also occurred when the mice were given a ketogenic diet composed primarily of fat.
Given this discovery, the researchers treated the animals’ pancreatic cancer with the drug eFT508, which disables the eIF4E protein, with the intention of blocking tumor growth. However, the tumors continued to grow, sustained by other fuel sources, such as glucose and carbohydrates.
Knowing that pancreatic cancer uses fat for fuel, and that eIF4E is most active during fat burning, the scientists then put the mice on a ketogenic diet, training the tumors to consume only fat. Then they gave the mice the drug eFT508, which cut off the cancer cells’ only source of sustenance. This caused the tumors to shrink.
“The field has struggled to firmly link diet to cancer and cancer treatments,” Ruggero says. “But to really connect these things in a productive way, you have to know the mechanism.”
Different combinations of diet and drugs will be needed to treat more forms of cancer. “We expect that most cancers will have other vulnerabilities,” Ruggero adds. “This is the basis for a new way of treating cancer with diet and personalized therapies.”
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Source: CNN Brasil
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