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When Less is More: How Cutting Calories Could Transform Cancer Treatment

Apr 8, 2025

By Marilyn Perkins | Illustrations by Kouzou Sakai

Early animal research shows reducing calories enhances radiation therapy.

Could this hold true in patients, giving them an active role in their care?

Caryn W. was diagnosed with breast cancer just last year. The 53-year-old mother of one had been feeling twinges of pain in the months leading up to a doctor’s appointment, and though she wasn’t scheduled for a mammogram until summer, her gynecologist urged her to move the scan up. The test showed some abnormalities, and Caryn went back for a biopsy. The results revealed early-stage carcinoma.

“It's earth-shattering to hear something like that,” says Caryn, a resident of southwest Philadelphia and an administrative assistant for a women’s club. “I was devastated. I needed to find out what to do and what was the best course of action.”

She found herself in the hands of Jefferson Health radiation oncologist Nicole Simone, MD, the Margaret Q. Landenberger Professor. Dr. Simone was launching a new clinical trial, and Caryn was intrigued. She’d receive radiation therapy first — to shrink the cancerous cells — then a straightforward procedure to remove any remaining tumor tissue. But, the most important part of Dr. Simone’s clinical trial wasn’t the radiation treatments or even the surgery: It was something Caryn would have to do every day in her own home, all on her own.

Dr. Simone wanted Caryn to cut her daily food intake by a quarter — not with the goal of dropping weight, but rather to help radiation destroy her cancer cells. It was an unconventional and controversial idea, but the trial is just the next step in an expanding body of research that suggests calorie restriction may be an untapped method for short-circuiting cancer cells, enhancing traditional treatments and killing tumors more efficiently. The approach could also empower cancer patients to be more involved in their own care.

Calorie Restriction — Stressor or Solution?

In 2010, Dr. Simone was studying the cellular effects of stress while working at the National Cancer Institute as an assistant clinical investigator. She was curious about how different types of stress, like radiation therapy or chemotherapy, changed the genetic makeup of cells, and what happened to them on a molecular level. Looking for new ways to induce stress, she started tapering down how much food she gave her cells; she expected that less food would weaken them and increase molecular signatures of stress. Instead, she found something unexpected — the slightly-hungry cells were actually getting stronger while the cancer cells got weaker.

She then tested out this discovery in mice, probing whether the cancer cells, weakened by calorie restriction, were more vulnerable to cancer treatment. She confirmed that starting animals on a calorie-restricted diet during radiation enhanced the therapy in models of breast cancer. Compared to control animals, the mice eating fewer calories had tumors that grew slower and metastasized less, and they ultimately survived longer.

Though it’s a new concept in cancer treatment, the health benefits of calorie restriction have been studied for the better part of a century. As far back as 1935, studies showed that low-calorie diets extended the lifespan of mice, and over the years, these benefits have been shown to hold true in humans, too: People who stick to lower-calorie diets tend to show fewer molecular signs of aging, have lower blood pressure and are less susceptible to diabetes.

According to Dr. Simone, calorie restriction’s benefits in cancer stem from the fact that healthy cells are better equipped to handle fluctuations in nutrition than cancerous cells. While healthy cells can meet their metabolic needs by drawing on different energy reserves, cancer cells have fewer options, meaning they’re more vulnerable.

“Normal cells can almost hibernate, whereas tumor cells can’t deal with the stress of radiation and calorie restriction at the same time,” says Dr. Simone. “Their machinery doesn’t work as well, and they die faster.”

Part of the “machinery” behind calorie restriction’s effects is the IGF-1R pathway — a cascade of cellular reactions responsible for breaking down sugars and helping cells grow. Cancer cells often have an overactive IGF-1R pathway – meaning they burn up lots of sugars and grow quickly – which is partly why cancer develops explosively compared to healthy cells. Restricting calories can hamstring this pathway, and therefore cancer growth. Furthermore, Dr. Simone has shown that cutting calories during radiation treatment in mice also stimulates the immune system, leading to a spike in cancer-fighting cells.

With a solid foundation of evidence that calorie restriction enhanced the effects of cancer treatment in animal models, Dr. Simone wanted to see if the same held true in patients.

“Nobody Will Ever Do This in Humans”

Dr. Simone’s theory was straightforward. Translating it into humans was less so. “When I was applying for grants somebody told me, ‘You know, nobody will ever do this in humans,’” says Dr. Simone.

In oncology, conventional wisdom emphasizes keeping cancer patients as comfortable as possible, and at a steady weight. As a medical student, Dr. Simone learned to encourage her patients to drink milkshakes and other high-calorie comfort foods, not to avoid them.

But, says Dr. Simone, keeping weight on isn’t as much of a concern as some would think. Though late-stage cancer patients can become dangerously frail, Dr. Simone is working with patients in earlier stages of the disease, who are unlikely to dip into underweight territory from a short diet. For these patients, calorie restriction can have a double benefit — more than one out of ten Americans have diabetes and two out of five are obese. These conditions are both associated with higher cancer risk and lower survival rates, but they can also be controlled partially through diet.

With all this in mind, Dr. Simone had to first demonstrate that a low-calorie diet was feasible and safe for cancer patients. In a pilot study of 35 women with breast cancer that began in 2013, she tested whether they could reduce their calories by 25% over the course of their radiation treatment. More than 80% of the women were able to stick to the diet, and they didn’t experience any negative effects from cutting calories. Moreover, patients started telling Dr. Simone they were glad to have something they could do to take their treatment into their own hands.

“Ever since I've been a resident, a lot of my patients have asked what they can do to help themselves,” she says. “This is letting patients take back some control.”

Caryn’s breast cancer surgeon Seye Adekeye, MD, PhD, who works closely with Dr. Simone, says that by employing a dietary approach, physicians hope to treat cancer more comprehensively, building on the current standard of care.

“Beyond the cancer cells, what about all the other things that are encouraging those cells to grow, like the tumor microenvironment?” says Dr. Adekeye. “We have to look at the whole body, not just the cancer.”

Now that Dr. Simone had shown it was possible — and even empowering — for cancer patients to eat a calorie-restricted diet, it was time to show that calorie restriction actually enhanced the effects of radiation.

A Cancer-Fighting Diet

In 2023, Dr. Simone started a clinical trial to test whether a 25% calorie reduction can enhance the tumor-shrinking effects of radiation that is administered before surgery.

After talking through her concerns with Dr. Simone and Dr. Adekeye, Caryn was ready to join. She first had a radiation planning session and would then undergo five subsequent radiation treatments. Back at home, she would work on her diet.

“It wasn’t too terrible,” says Caryn. She used to enjoy late-night snacks, but that habit was the first to go — no more popcorn, pie, or ice cream after dinner. She switched out soda for water and home-made iced tea, and subbed pie and cookies for trail mix. To satisfy her sweet tooth, she used a special blender to make “ice cream” out of frozen bananas and oat milk.

The changes seemed to work: After only five radiation sessions, new mammograms showed the cancer had shrunk. Dr. Adekeye operated on Caryn to remove the remaining tumor, and after the surgery, her cancer had significantly retreated. Full results from other patients in the trial will take time to be published, but Dr. Simone says Caryn isn’t the only success story; all patients had decreases in the size of their cancer, and in some, there was evidence of their breast cancer disappearing entirely through the combination of a calorie-restricted diet and radiation.

The trial, which aims to enroll 90 breast cancer patients, is still underway, with results expected within the next two years. Ultimately, the researchers plan to compare tumor remission rates of those undergoing radiation alone, to those using radiation alongside diet. The researchers hypothesize that the diet and radiation combination will prove more effective. And with even more clinical trials under her supervision, Dr. Simone believes she’ll soon have definitive results that can link the benefits of calorie restriction to cancer care on both a molecular and clinical level. As patients like Caryn complete their breast cancer care for early-stage cancer, Dr. Simone is also studying how intermittent fasting might improve outcomes for breast cancer that has metastasized to the brain. She’s also exploring how precise changes in diet — such as increasing or decreasing fat intake — might affect prostate cancer outcomes.

Top row: A cell signaling pathway called IGF-1, which turns on when the IGF-1 ligand binds to its receptor, is important for cell survival and reproduction. This pathway is overactive in cancer cells and drives tumor growth, making it harder for cancer treatments to work effectively. Bottom row: Calorie restriction reduces the number of IGF-1 receptors, hampering IGF-1 signaling. So when people eat fewer calories, they remove the “fuel” for this pathway, slowing down tumor growth. This could make radiation more efficient as the cancer cells are already weakened.

Meeting Patients Where They Are At

Though Caryn didn’t find the diet too challenging, Dr. Simone wanted to set up a support network for patients who did. She works with a team of students and specialists who call patients to check in on their diet and make sure they’re still getting the nutrition they need. She’s also collaborated with behavioral scientist Kuang-Yi Wen, PhD, to develop a text-messaging platform that helps participants stick to an eating schedule and monitor their food intake.

“That human touch is really what keeps a patient accountable for making change,” says Dr. Wen.

Having that support system is essential when every patient comes from a different background, with a different understanding of nutrition and access to healthy foods.

More than half of Dr. Simone’s patients come from a lower socioeconomic background. Her team ensures each patient’s treatment plan works for them, as some may struggle with the time, money or transportation necessary to make major dietary changes.

The beauty of the calorie-restricted diet, says Dr. Simone, is that anyone can eat a little less of the same foods. While some patients, like Caryn, choose to go the extra mile with bigger dietary changes, they can also achieve similar effects by simply changing portion sizes of the food they already eat.

Keeping their method accessible to everyone and understanding how social factors influence cancer are core principles of Dr. Simone’s team. “Your environment, your food, your access to health care, your financial status — all of these can cause stress within your body that impact cancer,” explains Dr. Adekeye. In her own research, she’s interested in how cancer disparities play out in Black women in particular, who die from cancer at higher rates than other racial and ethnic groups in the U.S.

One reason that may be is because Black women tend to have higher expression of IGF-1R, a protein implicated in cancer growth. Dr. Simone’s laboratory manager, Noëlle Francois, MS, found that calorie restriction and radiation quelled growth of cancer cells derived from Black women with breast cancer more than radiation alone. Francois, who recently completed her master’s degree thesis, hopes discoveries like these can help level the playing field in cancer treatment and provide Black patients with better care — and show that calorie restriction can be a valuable tool to treat more aggressive forms of cancer.

“A lot of people of color are left out of clinical trials,” says Francois. “If we want to care for a population, we should really get to know them and their specific needs.”

“ Tumor cells can’t deal with the stress of radiation and calorie restriction at the same time.”

Looking Forward

Though her last pathology report showed no signs of breast cancer, Caryn isn’t done with her treatment. She needs to take medication to keep the cancer at bay, and she deals with side effects daily. She’s awaiting upcoming mammograms to ensure the cancer hasn’t come back.

Still, she’s keeping up with the healthier diet she started during Dr. Simone’s trial. Though she no longer needs to restrict her calories, she’s grown used to subbing out pie for trail mix and exploring dairy-free options. For now, Caryn is working, volunteering with her church in her free time and spending time with her family. “I’m just trying to be optimistic and eat better,” she says.

Dr. Simone says that one day, she hopes cancer care will evolve so that patients like Caryn know which food choices they can make to play an active role in their treatment. She’s in the preliminary stages of investigating how certain types of tumors respond to different diets, with the goal of being able to recommend low-fat, low-glucose, or high-protein diets that target individual cancer genetics to enhance radiation and chemotherapy even more. But in the meantime, she says making small, healthier food choices is a good first step that all cancer patients could take.

“The old dogma was that diet didn’t matter during cancer therapy, but I think it does,” she says. “Even if you're not decreasing your calories, just making some better choices is a great start.”

Philanthropic Funding:

Jane Karatzas, the American Association for Cancer Research, the American Cancer Society, the American Institute for Cancer Research, Bristol-Myers Squibb Foundation, Inc., the Buck Cancer Foundation, the Ladies of Port Richmond, the Pfizer Independent Grants for Learning and Change, and the Willow Foundation Corporation.

When Less is More: How Cutting Calories Could Transform Cancer Treatment

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