A common dietary sugar found in soft drinks and processed foods may do more than add empty calories — it could help aggressive ovarian cancer spread. Scientists at The Wistar Institute have identified fructose as an unexpected driver of metastasis, uncovering a previously unknown mechanism by which chemotherapy-surviving cancer cells promote the disease's progression.
However, the researchers have cautioned that the findings are based on preclinical models and require validation in human studies before any dietary recommendations can be made. Nevertheless, they said fructose represents a potentially modifiable risk factor, unlike many genetic or biological factors associated with cancer progression.
The findings, published in the peer-reviewed journal Nature Ageing, suggest that cancer cells surviving chemotherapy remain biologically active and release fructose, which acts as a signalling molecule that enables neighbouring tumour cells to become more invasive and spread.
The researchers said the discovery offers a previously unrecognised explanation for why ovarian cancer frequently recurs and metastasises despite an initial response to treatment.
"Ovarian cancer is treated almost universally with platinum-based chemotherapy, and many patients respond well initially. However, recurrence is common and the disease often spreads within the abdominal cavity," the researchers noted, adding that metastasis accounts for nearly 90 per cent of deaths from the disease.
Traditionally, scientists believed that chemotherapy-resistant cancer cells contributed to recurrence primarily by surviving treatment. However, the new study suggests that the cells may continue to influence disease progression even after they stop dividing.
"Some cancer cells that survive chemotherapy aren't dividing anymore, but they're still biologically active," said Dr. Aidan Cole, a postdoctoral fellow at the Wistar Institute and the study's first author.
"Instead, they continue to release molecules that send signals to nearby cells. Our study is among the first to show that a nutrient—in this case, fructose—can act as one of those signals."
To investigate the phenomenon, researchers collected the substances released by chemotherapy-surviving cancer cells and introduced them into experimental models. They found that these released molecules alone were sufficient to significantly increase the ability of neighbouring cancer cells to spread.
"As far as we know, this is the first time anyone has shown, in a preclinical model rather than just a dish, that it's the molecules these cells release—not the cells themselves—that drive the cancer's spread," Dr. Cole said.
Further analysis identified fructose as the critical signalling molecule responsible for this effect.
The researchers made another unexpected observation. Even in the absence of chemotherapy, exposure to the high concentrations of fructose commonly found in sugar-sweetened beverages appeared capable of promoting similar changes associated with cancer spread.
Although the findings do not establish that consuming fructose directly causes cancer metastasis in patients, they suggest that dietary sugars may influence tumour behaviour in ways that have not previously been recognised.
To understand how fructose promotes metastasis, the team employed advanced molecular analyses, including CRISPR-based genetic screening. They discovered that fructose suppresses cholesterol production within neighbouring cancer cells.
According to the researchers, cholesterol plays an important structural role by helping cells adhere to one another. Reduced cholesterol weakens these cellular connections, allowing malignant cells to detach more easily and spread to other tissues.
The findings also have implications for patients taking cholesterol-lowering drugs.
Statins, widely prescribed to reduce cholesterol levels, were found to produce a similar effect by weakening cell-to-cell adhesion, potentially facilitating cancer cell escape under experimental conditions.
"We haven't tested this effect in patients yet, but it raises questions about combining cholesterol-lowering drugs with chemotherapy, especially since ovarian cancer is most common in postmenopausal women who are often already on statins," said Dr. 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 senior author of the study.
The researchers stressed that the findings should not prompt patients to discontinue statins, as the study does not establish that the medicines worsen cancer outcomes. Instead, they believe the observations warrant further clinical investigation to better understand whether cholesterol-lowering therapy influences responses to chemotherapy.
Dr. Aird said the team believes similar biological mechanisms may operate in other cancers that spread within the abdominal cavity, including pancreatic, colorectal and liver cancers.
"We think other cancers that spread within the torso—pancreatic, colon and liver—could behave similarly. We can't call it universal yet, but we think the effects are not just limited to ovarian cancer," she said.
The researchers have already begun follow-up studies to determine whether the fructose-driven signalling pathway is reproducible across different tumour types.
Experts said the findings highlight the growing recognition that cancer progression is influenced not only by genetic mutations but also by the tumour micro-environment, metabolism and interactions between surviving cancer cells and surrounding tissues.
If confirmed in clinical studies, the discovery could eventually pave the way for new therapeutic strategies that target metabolic signalling pathways alongside conventional chemotherapy. It also underscores the need to better understand how diet, metabolism and commonly used medications interact with cancer treatment.
