The Faeth site just went live, and the scientific founders’ groundbreaking work was just featured in Science:
“Special diets might boost the power of drugs to vanquish cancers
“Scientists including Vousden, who cofounded a company with Cantley to test diet-drug combinations in cancer trials, are unraveling the molecular pathways by which slashing calories or removing a dietary component can bolster the effects of drugs. In mice with cancer, “the effects are oftentimes on the same order of magnitude as those from the drugs that we give patients. That’s a powerful thing to think about“
In one trial, participants will shop for and prepare meals according to instructions. In the other, the company Faeth Therapeutics that Cantley co-founded will ship meals to patients to help them stay on track.
If those trials show the ketogenic diet helps curb tumor growth for a year or two longer than the PI3K inhibitor otherwise would, the diet “could become the standard of care,” Cantley says. “That will be what physicians will tell patients to do.”
A ketogenic diet may enhance other cancer treatments, too. Immunologist Laurence Zitvogel of the Gustave Roussy Institute in France recently studied mice with skin, kidney, or lung cancers receiving a drug known as a checkpoint inhibitor that helps the immune system’s T cells kill tumors. In animals on a ketogenic diet, the ketone bodies they produced boosted the T cells’ power, her team reported in January. Rabinowitz and collaborators have begun enrollment for a 40-person trial to see whether the diet can enhance the impact on pancreatic cancer of a chemotherapy cocktail.
OTHER RESEARCHERS ARE exploring an even more precise dietary limitation: cutting out specific amino acids, best known as the building blocks of proteins but also key to many other metabolic processes. Vousden unexpectedly veered into that line of research while studying a cancer-preventing gene called p53. The protein it encodes can trigger cells that have DNA damage to self-destruct, stopping them from turning cancerous. The gene is mutated in many tumors, allowing unrestrained growth.
But in 2005, a U.S. lab reported a surprising finding: The intact p53 protein helps healthy cells survive when glucose is scarce, suggesting p53-mutated cancer cells are especially vulnerable to glucose limitation. Vousden wondered whether the protein also helps cells survive a shortage of other, less explored nutrients, such as amino acids—and whether the mutated p53 in cancer would make the cells less resilient.
To find out, her postdoc Oliver Maddocks [and Faeth Head of Research] methodically removed various amino acids from cancer cells’ culture medium. Many types of cancer cells grew more slowly when deprived of two related amino acids, serine and glycine, and deleting p53 ramped up that effect. The scientists then tested the effects of a serine- and glycine-free diet in mice. Maddocks and Vousden reported in 2013 and 2017 that the special diet slowed cancer growth and extended the lives of mice implanted with colon cancer cells lacking p53 as well as in mice engineered to develop lymphoma or colon tumors. Cells need serine or glycine to make a compound that sops up DNA-damaging free radicals, and the deprivation made tumor cells more sensitive to that oxidative stress. Radiation and some chemotherapies kill cells by generating free radicals, so the results suggested the diet could prime tumors for those treatments.
Similar findings have emerged for other amino acids. Limiting the essential amino acid methionine appears to amplify the effects of radiation and chemotherapy in mice with colon cancer and sarcomas. And removing asparagine, an amino acid abundant in asparagus, from mouse diets curbed the spread of metastatic breast cancer, suggesting the diet could enhance drug treatments.
As with serine, depriving mice of one of those amino acids apparently disrupts metabolic cycles by which cancer cells respond to oxidative stress, synthesize DNA, and turn genes off and on.
The company Vousden and Cantley founded, Faeth (Welsh for nutrition), is gearing up to test amino acid–depleted diets in two clinical trials this year. Faeth, also cofounded by Maddocks, will combine chemotherapy with a shake lacking specific amino acids, delivered to participants’ homes alongside other meal components, such as salads. The researchers got support from private investors after failing to win research grants for their idea, says Maddocks, now at the University of Glasgow. “It’s quite out of the box.”
Maddocks expects the cancer-diet field will take years to move from “piecemeal forays” to a clear understanding of each diet’s pros and cons. Establishing that a specific diet works well enough to become part of routine clinical care also will take time. But Zitvogel says fighting cancer with diet is no longer a fringe idea. The field is at the start of “a new era where people will really take diet seriously into account,” she says. “The time is ripe.”
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