- Ovarian cancer, doctors explain, can be hard to treat as it may go undiagnosed for a long time. That also makes the cancer more likely to spread through the body.
- Researchers from The Wistar Institute at the University of Pennsylvania wanted to know what, exactly, makes it easier for ovarian cancer to spread, particularly in cases where it has already been subjected to chemotherapy.
- Through experiments in animal models they found that one particular nutrient — namely, fructose — can help boost the signalling of cancer cells, thus facilitating metastasis.
In 2026 alone, an estimated 21,010 people will have received a new diagnosis of ovarian cancer in the United States. This type of cancer has a 52% relative 5-year survival rate, which doctors and other medical experts are working hard to improve.
One of the most common types of treatment for ovarian cancer is chemotherapy but this does not result in the cancerous cells clearing up in every case, which can mean that the cancer may end up spreading further throughout the body, a phenomenon known as metastasis.
Recently, researchers from The Wistar Institute at the University of Pennsylvania, PA, set out to gain a better understanding of the mechanisms behind ovarian cancer metastasis.
“Chemotherapy remains one of the best treatment strategies for many cancers, including ovarian cancer. Unfortunately, some cancer cells can survive chemotherapy, and those cells release factors that influence cancer progression,” Katherine Aird, PhD, Professor and Co-Leader in the Molecular and Cellular Oncogenesis Program at the Ellen and Ronald Caplan Cancer Center, The Wistar Institute, told Medical News Today.
Aird is the senior author of a new preclinical study, which looked at how ovarian cancer cells that escape chemotherapy are able to spread throughout the body.
The study’s findings, which appear in Nature Aging, point the finger at a seemingly surprising culprit: fructose.
Cancers affecting the female reproductive system, such as ovarian cancer, “frequently present with vague or no symptoms in its early stages, such as bloating, pelvic pain, and feeling full quickly, which can be mistaken for other common conditions,” said Ami Vaidya, MD, Co-Chief of the Division of Gynecologic Oncology at the Hackensack University Medical Center, who was not involved in the study.
Thus, Vaidya noted, “most cases are diagnosed at an advanced stage when the cancer has already spread.”
Moreover, according to Nathan Goodyear, MD, an integrative medicine physician, board-certified in obstetrics and gynecology, co-founder of Williams Cancer Institute, who was likewise not involved in this study:
“Ovarian cancer is uniquely challenging because it is often biologically primed for metastasis long before it is clinically detected. Moreover, metastasis occurs far earlier in high-grade serous ovarian cancer than previously thought possible. Once metastatic, these disseminated tumor cells can persist in dormant or slow-proliferative states, hiding below the surface of detection of current lab and imaging modalities.”
In their recent study paper, the researchers explain that chemotherapy commonly induces a response called “cellular senescence” in cancer cells.
When a cell becomes senescent, it becomes, in some sense, stable, as it stops dividing further. However, the cell remains “alive.”
The question that then arises is: If senescent cancer cells stop dividing, how, then, is the cancer still able to spread throughout the body?
Past research has suggested that the spread may not always be a result of straightforward cellular division.
Instead, senescent cancer cells that have survived chemotherapy are able to secrete chemical messengers that then induce certain responses in the cells around them, thus allowing the cancer to continue spreading.
With this premise in mind, the researcher team at The Wistar Institute collected ovarian cancer cells that had been exposed to chemotherapy and survived. They were then able to further collect the signaling molecules released by those cells and expose other cancer cells to them, to see how they would respond.
Using animal models, the researchers were able to confirm that, just by being exposed to those signaling molecules, the cancer cells increased their ability to spread.
Notably, the researchers also found that senescent cancer cells that had survived chemotherapy released fructose, and that it was this nutrient that played a key role in “telling” other cancer cells to multiply.
“We discovered that cells surviving chemotherapy release fructose, the same sugar found in fruits and high-fructose corn syrup,” Aird told MNT.
“This fructose can be processed by cancer cells in a way that makes them more capable of spreading by decreasing the cellular glue that holds cancers together.”
— Katherine Aird, PhD
That “cellular glue,” as it turns out, is cholesterol. According to the researchers’ analyses, the “messaging” fructose lowers cholesterol production when it reaches other cancer cells.
This lack of cholesterol is what assists those cancer cells in spreading faster: Essentially, cholesterol holds clusters of cells together. When the cholesterol is lacking, the cells are able to detach and spread.
The team also found something else, namely “that a high fructose diet alone increased cancer spread,” Aird told us.
High levels of dietary fructose — from sugary beverages, for example — appeared to speed up the spread of cancer in the absence of chemotherapy.
While the researchers have not confirmed to what extent dietary choices can influence the spread of ovarian cancer, this finding does seem to encourage caution and adherence to healthy, less sugary diet types.
“There are many potential implications to our work, although […] this is a preclinical study, and none of our findings have yet been confirmed in humans,” noted Aird.
“The first implication,” she said, “is that chemotherapy can have negative consequences. This doesn’t mean we should stop giving patients chemo, but instead that we need to learn more about these negative effects so that we can prevent them.”
“The second is that a high fructose diet could lead to worse cancer outcomes. Finally, we identified that fructose is processed in cancer cells in a way that leads to decreased cholesterol. This could have potential implications for patients on statins, drugs that lower cholesterol.”
— Katherine Aird, PhD
“All of these need to be further studied before we can make an definitive claims for ovarian cancer patient care,” cautioned the study author.
Goodyear further commented on how this study changes experts’ perspective on fructose and its potential role in health. “In this study, the authors showed that fructose sits at the crossroads between chemotherapy-induced senescence and metastasis,” he told us.
“Most are familiar with fructose as a component of the rapid rise of ultraprocessed foods post-1970s, driven by high-fructose corn syrup (HFCS),” said Goodyear. “Yet here, fructose is not the microbiome reprogrammer, the immune modulator, or simply ‘fructose bad’.”
“This study reframes fructose as the fuel that drives metastatic dissemination via chemotherapy-induced senescent cell metabolic reprogramming that allows neighboring cancer cells to exploit [other] cancer cells,” he emphasized.
“Our reaction should be a great pause. If chemotherapy induces the means to exploit fructose to enable metastasis and the success of metastasis, then increased availability of the fructose substrate in combination would pose a significant metastatic risk. Of note, a common thought is that diet does not matter when it comes to support of conventional cancer treatment. Yet, most chemotherapy practices supply ultraprocessed foods, in candy bars, baked goods, and soft drinks, increasing the metabolic driver in a reprogrammed environment which can exploit their availability. The authors of this study directly refute these outdated claims based on mechanisms.”
— Nathan Goodyear, MD
“The findings in the recent study represent a significant paradigm shift in understanding cancer metastasis,” said Vaidya, who also qualified the findings on the role of fructose in cancer metastasis as “the most striking discovery.”
According to her, this study reveals important new avenues for exploration in the context of ovarian cancer therapy, but there is still a long way to go in terms of validating the findings:
“This crucial connection between chemo-resistance and metastasis opens up promising new avenues for therapeutic strategies, potentially including dietary interventions or drugs that target this specific fructose-cholesterol pathway. While the researchers suggest this mechanism could be relevant for other abdominal cancers and raise questions about the interplay with common medications like statins, it is important to remember that these are preclinical findings that require further validation in human studies before clinical applications can be considered.”
— Ami Vaidya, MD
Goodyear likewise told MNT that “this study is important because it shifts thinking away from chemotherapy as simply a tumor-killing therapy to chemotherapy as a treatment that also changes the biological function of surviving cells.”
In his view, “one of the most important discoveries in this study is that metabolism — not genetics — is the principal driver of metabolic-reprogrammed metastasis.”
Going forward, Aird and her colleagues would like “to find a way to decrease fructose production by the cells that survive chemotherapy,” as she explained to MNT.
“Excitingly, there is an FDA-approved drug used in diabetic patients that may be able to do this. We are currently performing additional preclinical studies to examine this possibility,” Aird told us.
“We are also interested to identify other nutrients that are released by cells the survive chemotherapy. We think that this could inform additional studies on the negative consequences of chemotherapy. Finally, we hope to collaborate with physicians to understand whether dietary intake is associated with patient outcomes. This is our ‘pie in the sky’ goal, but one that I believe would be the most impactful. We could take knowledge found from these studies back into the lab to understand at a cellular and molecular level how diet influences cancer.”
— Katherine Aird, PhD
“Ultimately, while this [recent] discovery represents a significant scientific step forward that may lead to more effective treatments down the road, patients should continue to rely on their oncology team for all current health and treatment decisions,” Vaidya advised.
“Regarding ovarian cancer prevention, while there is no guaranteed method, risk can be significantly lowered through factors like using oral contraceptives, pregnancy, and maintaining a healthy lifestyle,” she noted.
“For high-risk individuals, especially those with genetic mutations like BRCA, genetic counseling and risk-reducing surgery are the most effective options,” said the oncologist.
“[M]aintenance of a healthy body weight, routine physical activity, smoking cessation, and adherence to dietary
patterns rich in whole-food vegetables, fruits, legumes, whole grains, and healthy fats while limiting, better yet eliminating, ultra-processed foods” can also help with prevention, added Goodyear.
“Since no reliable routine screening test exists, preventing metastasis after a diagnosis becomes the central goal of treatment. This is primarily achieved through a comprehensive and aggressive approach combining cytoreductive (debulking) surgery to remove as much cancerous tissue as possible, followed by systemic treatments like chemotherapy and targeted therapies, such as PARP inhibitors, to eliminate remaining cells and prevent recurrence.”
— Ami Vaidya, MD
“Ultimately, diligent, long-term surveillance after treatment is critical to monitor for and manage any potential spread of the disease,” she emphasized.
