A new study has found a possible link between fructose, a common dietary sugar, and the spread of an aggressive form of ovarian cancer.
Researchers at The Wistar Institute found that cancer cells that survive chemotherapy can release fructose, which may act as a chemical signal and encourage nearby cancer cells to spread.
The findings, published in Nature Aging, point to a previously unknown way in which cancer cells left behind after treatment may contribute to the spread of the disease.
“Some cancer cells that survive chemotherapy aren't dividing anymore, but they're still biologically active,” said 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,” he said.
Why ovarian cancer often returns
Most ovarian cancer patients receive platinum-based chemotherapy, which can initially be effective. However, the disease often returns and spreads through the abdominal cavity.
This spread, known as metastasis, is responsible for about 90% of deaths from ovarian cancer, according to the researchers.
Earlier studies suggested that cancer cells that survive chemotherapy may contribute to recurrence by releasing various chemical signals.
To study this process, Cole and his colleagues separated the surviving cancer cells from the substances they produced. They then exposed other cancer cells to those substances.
The researchers found that the released substances alone significantly increased the ability of other 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,” Cole said.
Fructose may act as a signal
The researchers then looked for the specific substance responsible for the effect.
Their analysis showed that chemotherapy-surviving cancer cells produced fructose, which acted as a signal that encouraged nearby cancer cells to spread.
They also found that high levels of dietary fructose, similar to amounts found in some sugary drinks, could promote cancer spread in their experimental models even without chemotherapy.
The finding raises questions about whether diet could influence cancer progression.
Fructose is widely consumed, particularly in the United States, where high-fructose corn syrup can account for a significant share of daily calorie intake for some people.
However, the researchers stressed that they have not yet tested whether reducing fructose intake improves outcomes for cancer patients.
How fructose may help cancer cells spread
The researchers next examined how fructose could make cancer cells more likely to move.
Using several analytical techniques, including a CRISPR-based screening method, they found that fructose reduced cholesterol production in nearby cancer cells.
Cholesterol helps maintain connections between cells, acting partly like biological glue. When cholesterol levels decrease, those connections can weaken, potentially allowing cancer cells to separate and move more easily.
The researchers said this could help explain how a common nutrient may influence the physical behaviour of cancer cells.
Questions about cholesterol-lowering drugs
The findings also raised questions about statins, drugs commonly used to lower cholesterol.
In their experiments, the researchers found that statins alone weakened connections between cancer cells and made it easier for them to separate.
However, the researchers stressed that the findings do not mean patients should stop taking statins or any other prescribed medicines.
“We haven't tested this effect in patients yet, but it raises questions about combining cholesterol-lowering drugs with chemotherapy,” said Katherine Aird, a professor and senior author of the study at The Wistar Institute.
She noted that the issue may be particularly relevant because ovarian cancer is more common among postmenopausal women, many of whom may already take statins.
Could other cancers be affected?
The researchers are now investigating whether the same fructose-related mechanism could also play a role in other cancers.
“We think other cancers that spread within the torso — pancreatic, colon, liver — could behave similarly,” Aird said.
“We can't call it universal yet, but we think the effects are not just limited to ovarian cancer,” she added.
Aird and Cole have begun planning further studies to determine whether similar findings occur in other types of cancer.
The researchers emphasised that the current findings are preclinical and do not yet establish that eating fructose causes cancer to spread in people.
