Fructose Identified as Surprise Driver of Ovarian Cancer Metastasis After Chemotherapy
Key Insights
A Wistar Institute study published in Nature Aging identifies fructose as a signaling molecule that promotes ovarian cancer (search) spread after chemotherapy.
Chemotherapy-surviving cells release fructose, which suppresses cholesterol in neighboring cells, reducing cellular adhesion and enabling metastasis.
Even without chemotherapy, high dietary fructose intake—such as from sugary drinks—can signal cancer cells to spread, suggesting nutrition may influence cancer progression.
A new study from The Wistar Institute has revealed that fructose, a simple sugar ubiquitous in modern diets, acts as a key signaling molecule that drives the spread of ovarian cancer (search) following chemotherapy. Published in Nature Aging, the findings uncover a previously unrecognized mechanism by which treatment-surviving tumor cells promote metastasis and raise provocative questions about the interplay between diet, cholesterol-lowering medications, and cancer progression.
The research addresses a central challenge in ovarian cancer (search) treatment: although patients nearly universally receive platinum-based chemotherapy (search) and many respond well initially, the disease recurs in most patients and spreads through the abdominal cavity. That metastatic spread accounts for roughly 90% of ovarian cancer-related deaths.
Surviving Cells as Active Signalers
Prior research has established that cancer cells not killed by chemotherapy contribute to recurrence, partly through their ability to release a complex mix of signaling molecules. The Wistar team, led by Aidan Cole, Ph.D., a postdoctoral fellow, and senior author Katherine Aird, Ph.D., designed an experiment to isolate the effect of these molecular signals.
“Some cancer cells that survive chemotherapy aren't dividing anymore, but they're still biologically active,” said Cole. “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.”
The researchers collected the molecules released by chemotherapy-surviving cells and demonstrated 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 dish, that it's the molecules these cells release—not the cells themselves—that drive the cancer's spread,” Cole noted.
Fructose as the Messenger
Further analysis pinpointed fructose as the signal produced by surviving cells that drives increased metastatic behavior. The team discovered that fructose suppresses cholesterol within neighboring cells. Cholesterol serves as a biological glue that helps cells adhere to one another; decreased cholesterol levels allow cancer cells to more easily escape and spread.
The fructose finding extends beyond chemotherapy contexts. The researchers found that even without chemotherapy treatment, consuming the high levels of fructose found in sugary drinks can also signal cancer cells to spread. This is particularly significant given that high-fructose corn syrup accounts for approximately 8–20% of daily caloric intake in some individuals in the United States.
Unlike many cancer risk factors beyond patient control, fructose consumption can be modified through dietary choices. While the effectiveness of limiting fructose intake has not yet been tested directly in patients, the study raises the possibility that nutrition could influence cancer progression in previously unrecognized ways.
Statins (search) and Cholesterol: A Clinical Question
The finding that fructose lowers cholesterol production carries important clinical implications. Statins (search), cholesterol-lowering drugs taken by approximately 39 million people in the United States, also reduce cholesterol production. The research team found that statins alone decreased the intercellular adhesion that keeps cells together, promoting escape.
“We haven't tested this effect in patients yet, but it raises questions about combining cholesterol-lowering drugs with chemotherapy, especially since ovarian cancer (search) is most common in postmenopausal women who are often already on statins (search),” said Aird.
The researchers stress, however, that there is not yet any reason for patients already taking statins (search) to discontinue them. Follow-up experiments are being designed to test whether these findings apply to other cancer types beyond ovarian cancer (search).