Fructose, a Common Dietary Sugar, May Help Cancer Cells Break Free and Spread, Researchers Say in New Study

Cancer cells that survive chemotherapy may release a common dietary sugar to help neighboring tumor cells break loose and spread throughout the body, according to a new study from The Wistar Institute that identifies a previously unknown pathway behind one of cancer’s deadliest processes.

The research, published in the journal Nature Aging, focused on ovarian cancer and found that fructose, a sugar widely consumed in the American diet, can act as a chemical signal released by cells that remain in the body after chemotherapy treatment. That signal appears capable of making nearby tumor cells more likely to detach and metastasize, a process responsible for the vast majority of deaths from the disease.

Cells that survive treatment keep sending signals

Nearly all ovarian cancer patients receive platinum-based chemotherapy, and the treatment typically produces a strong initial response. Despite that, the cancer returns in most patients and commonly spreads throughout the abdominal cavity, a process responsible for roughly 90% of deaths tied to the disease.

Researchers have previously suspected that cancer cells surviving chemotherapy might contribute to that recurrence by releasing a mix of signaling molecules, even after they stop actively dividing. To test that idea more directly, the Wistar-led research team designed an experiment separating surviving cancer cells from the substances those cells released into their environment.

“Some cancer cells that survive chemotherapy aren’t dividing anymore, but they’re still biologically active,” said Aidan Cole, a postdoctoral fellow in the lab of Katherine Aird at The Wistar Institute and the study’s first author. He explained that the cells continue releasing molecules that send signals to nearby cells, and the study is among the first to show that a nutrient, in this case fructose, can function as one of those signals.

When the team exposed other cancer cells only to the molecules released by chemotherapy-surviving cells, without exposing them to the surviving cells themselves, that exposure alone was enough to significantly boost the treated cells’ ability to spread. Cole said the finding marked the first time researchers had shown, in a preclinical model rather than simply in a lab dish, that it’s the released molecules rather than the surviving cells themselves that appear to drive the cancer’s spread.

Diet may play a larger role than previously understood

After identifying fructose as a key signaling molecule, researchers also tested whether high levels of dietary fructose, comparable to amounts found in sugary drinks, could encourage cancer spread even without prior chemotherapy exposure. That test suggested the sugar alone could promote spread, raising the possibility that everyday dietary habits might influence how the disease progresses over time.

That finding carries added significance given how widely fructose is consumed in the United States. High fructose corn syrup can account for roughly 8% to 20% of daily calorie intake for some people, according to the study. Unlike many cancer risk factors that patients have little control over, researchers noted that fructose intake is one variable people can potentially modify through diet, though they cautioned that no studies have yet tested whether reducing fructose consumption actually improves outcomes for patients.

How fructose may help cancer cells escape

To understand the mechanism behind fructose’s effect, researchers used several large-scale analytical techniques, including a CRISPR gene-editing screen, and found that fructose appears to lower cholesterol production inside neighboring cancer cells. Cholesterol plays an important structural role in helping cells remain attached to one another, functioning similarly to a biological adhesive. When cholesterol levels drop, those cellular bonds weaken, making it easier for cancer cells to separate from surrounding tissue and move elsewhere in the body.

A possible connection to a widely used class of drugs

The discovery that reduced cholesterol production may promote cancer spread also raised questions with potential clinical relevance, given that statins, cholesterol-lowering drugs used by an estimated 39 million people in the United States, work through a similar mechanism. In laboratory testing, statins alone were found to weaken the connections between cancer cells, making it easier for them to separate and spread, prompting researchers to begin investigating whether the drugs could interact with chemotherapy in ways not previously understood.

The research team was careful to stress that the findings should not be interpreted as a reason for patients to stop taking statins or any other prescribed medication. “We haven’t tested this effect in patients yet,” said Katherine Aird, professor and co-leader of the Molecular and Cellular Oncogenesis Program at The Wistar Institute’s Ellen and Ronald Caplan Cancer Center and the study’s senior author. She noted that the findings raise questions worth exploring further, particularly because ovarian cancer is most common in postmenopausal women, many of whom are already taking statins for cardiovascular health reasons unrelated to their cancer treatment.

Broader implications beyond ovarian cancer

Researchers involved in the study believe the fructose-driven pathway they identified may extend beyond ovarian cancer to other cancers that commonly spread within the torso, including pancreatic, colon and liver cancers. “We think other cancers that spread within the torso — pancreatic, colon, liver — could behave similarly,” Aird said, while cautioning that the team cannot yet call the effect universal across cancer types based on current evidence.

Aird and Cole have already begun planning follow-up studies aimed at determining whether the same mechanism can be reproduced in other forms of cancer, work that could help clarify how widely applicable the fructose-related pathway may be across different types of tumors.

A large, multi-institution collaboration

The study involved dozens of researchers from institutions including the University of Pittsburgh School of Medicine, the University of Pittsburgh, Temple University’s Lewis Katz School of Medicine, the H. Lee Moffitt Cancer Center, the University of Colorado Boulder and Anschutz Medical Campus, and the Ludwig Institute for Cancer Research at the University of Lausanne, alongside researchers at The Wistar Institute. The work was funded by multiple grants from the National Institutes of Health, along with support from organizations including the American Cancer Society, the Ovarian Cancer Research Alliance, the Congressionally Directed Medical Research Program, and the Chan Zuckerberg Initiative, among others.

While the findings offer a new and previously unrecognized explanation for how ovarian cancer may spread after chemotherapy, researchers emphasized that the connection between dietary fructose intake and cancer outcomes in actual patients remains untested. Determining whether reducing fructose consumption, adjusting statin use, or other interventions could meaningfully affect cancer progression in humans will require additional clinical research, a process the study’s authors say they are now working to pursue.