Ovarian cancer is treated almost universally with platinum-based chemotherapy, and many patients respond well at first. But the disease recurs in most patients and almost always spreads through the abdominal cavity — and that spread, called metastasis, accounts for roughly 90% of deaths from the disease.
A new study from The Wistar Institute, published in Nature Aging, has uncovered an unexpected link between fructose — a common dietary sugar — and that lethal spread. Cancer cells that survive chemotherapy are no longer dividing, but they remain biologically active, releasing molecules that signal nearby cells. Using a unique experiment, researchers collected those molecules and found that, on their own, they significantly increased 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 dish, that it's the molecules these cells release — not the cells themselves — that drive the cancer's spread," said first author Aidan Cole, Ph.D. The key messenger turned out to be fructose: surviving cells make it and send it as the signal to spread. Strikingly, even without chemotherapy, consuming high levels of fructose — the kind found in sugary drinks — could trigger the same signal, with high-fructose corn syrup accounting for roughly 8-20% of daily caloric intake in some Americans.
The team then traced why fructose makes cancer cells spread. Through a CRISPR screen and other large-scale analyses, they found that fructose suppresses cholesterol production in neighboring cells. Cholesterol normally acts like a biological glue that keeps cells stuck together; with less of it, cells escape more easily. The finding has clinical implications: statins, taken by about 39 million people in the United States, also lower cholesterol — and the team found statins alone weakened that glue, promoting escape. They are now investigating whether these medications could interfere with chemotherapy, while stressing that patients should not 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 senior author Katherine Aird, Ph.D. The researchers believe other cancers that spread within the torso — pancreatic, colon, liver — could behave similarly, and they are designing follow-up experiments to test the mechanism more broadly.
