Fructose identified as driver of ovarian cancer spread after chemotherapy

A study has linked fructose – a common dietary sugar – to the spread of an aggressive form of ovarian cancer, raising questions about diet and statin use during chemotherapy

A study from The Wistar Institute, Philadelphia, Pennsylvania, USA has uncovered an unexpected link between fructose – a sugar found widely in the diet – and the spread of an aggressive form of ovarian cancer. The research has shown that cancer cells that survive chemotherapy send signals to neighbouring tumour cells to help them become more able to spread. The researchers have identified fructose as a key messenger in this process, and the findings reveal a route, not previously recognised, by which chemotherapy-surviving cells may drive the further spread of cancer.

“Some cancer cells that survive chemotherapy [may not be] dividing anymore but they are still biologically active,” said Dr Aidan Cole, the first author of the study, and a postdoctoral fellow in the laboratory of Professor Katherine Aird at The Wistar Institute.

“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,” he said.

Ovarian cancer is treated almost universally with platinum-based chemotherapy and many patients respond well at first. However, the disease recurs in most patients and almost always spreads throughout the abdominal cavity. This metastasis accounts for around 90 per cent of deaths from the disease.

Previous research has suggested that cancer cells not killed by chemotherapy play a part in recurrence, in part through their ability to release a complex mix of signalling molecules. Cole and his colleagues began their research with an experiment where they collected the molecules released by chemotherapy-surviving cells and found that these factors alone could significantly increase the spread of cancer cells.

“As far as we know, this is the first time anyone has shown, in a preclinical model rather than just a [petri] dish, that it’s the molecules these cells release – not the cells themselves – that drive the cancer’s spread,” said Cole.

That finding led the team to look for what was being released to cause the cancer cells to spread. Fructose, it turned out, was being made by the surviving cells and sent as the signal for increased spread. Even more notable, the researchers found that, without chemotherapy treatment, high levels of fructose, of the kind found in sugar-sweetened drinks, can also signal this cancer to spread.

The fructose finding is especially significant because it raises the possibility that dietary change could help to shape how cancer progresses. This is particularly relevant given the prevalence of fructose consumption in the US, where high-fructose corn syrup accounts for around 8–20 per cent of daily caloric intake in some individuals.

Unlike many cancer risk factors outside a patient’s control, fructose intake can be modified through diet. The effectiveness of limiting fructose intake has not yet been tested directly in patients but the study raises the possibility that nutrition could influence cancer progression in ways not previously recognised.

The researchers next sought to establish why fructose increases the spread of cancer cells. Through a range of large-scale analytical techniques, such as a screen based on CRISPR, the team found that fructose suppresses cholesterol within neighbouring cells. Cholesterol acts as a kind of biological ‘glue’ that holds cells together, so a reduction in cholesterol allows cells to escape and spread more easily.

This finding, that fructose lowers cholesterol production, carries clinical significance. Statins, taken by 39 million people in the US, also lower cholesterol production, and the team found that statins alone reduced the adhesion between cells, which allowed them to escape more easily. The research team has begun to examine whether these medications could interfere with the effects of chemotherapy, though they stress that this is not a reason for patients to stop taking them.

“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 Professor Katherine Aird, senior author of the study and co-leader of the Molecular and Cellular Oncogenesis Programme in the ‘Ellen and Ronald Caplan Cancer Center’ at The Wistar Institute.

The researchers have also begun to look into how this mechanism might extend beyond ovarian cancer.

“We think other cancers that spread within the torso – pancreatic, colon, liver – could behave similarly. We can’t call it universal yet but we think the effects are not just limited to ovarian cancer,” said Aird.

For further reading please visit: 10.1038/s43587-026-01172-5.