New Findings on Prostate Cancer: From Treatment Resistance to Diet

Ultra-processed foods (UPFs) are becoming increasingly common in the Western world. These industrially produced foods include soft drinks, packaged cereals, snacks, and processed meats. They are typically made from refined fats, oils, sugar, starch, salt, and other additives designed to enhance flavor, texture, and shelf life—often at the expense of nutritional quality. A growing body of research has established a link between increased consumption of UPFs and a variety of health problems. Scientists have proposed various mechanisms through which these foods could potentially contribute to the development of cancer, including metabolic disorders, increased inflammation and oxidative stress, and changes in the gut microbiome. To date, however, there is relatively little evidence that high consumption of UPFs is specifically linked to prostate cancer in men.

Higher UPF Intake Is Linked to Prostate Cancer

New research from the Charles E. Schmidt College of Medicine at Florida Atlantic University suggests that men who consume more UPFs may have an increased risk of developing prostate cancer. About one in eight men will be diagnosed with prostate cancer during their lifetime. The study, published in the American Journal of Medicine, analyzed nationally representative data from 17,024 U.S. men aged 18 and older who participated in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2023.

To estimate the consumption of highly processed foods, the researchers analyzed two 24-hour dietary recall forms from each participant and calculated the percentage of daily calories derived from highly processed foods. The foods were classified using the validated and widely used NOVA system. The participants were then divided into four groups, ranging from those who obtained less than about 20% of their calories from highly processed foods to those who obtained more than 44% from them.

The Risk of Prostate Cancer Increased by About 30 Percent

Compared with men in the group with the lowest UPF intake, those in the three groups with higher intake had a 29% increased risk of prostate cancer. Men in the two groups with the highest intake had a 30% increased risk. The association remained statistically significant after the researchers adjusted for age, race and ethnicity, smoking, and poverty status. After these adjustments, the increased risk ranged from 24% to 31%.

Men in the group with the highest intake showed a possible 34% increase in prostate cancer risk. However, this result did not reach statistical significance, which the researchers believe may be due to the smaller number of prostate cancer cases in this group.

“Among adult men in this nationally representative U.S. population sample, those who consumed larger amounts of UPFs had a significantly higher risk of developing prostate cancer later in life,” said Dr. Charles H. Hennekens, FACPM, FACC, lead author and holder of the “First Sir Richard Doll” Chair in Medicine and Preventive Medicine in the Department of Medicine and the Department of Population Health at FAU’s Medical School. “These findings add to the emerging evidence that UPFs have significant adverse health effects and underscore the need for large-scale observational studies and randomized trials to adequately test this hypothesis.”

Growing Health Concerns Regarding Ultra-Processed Foods

Previous research has identified a link between higher consumption of ultra-processed foods (UPFs) and an increased risk of overweight and obesity, metabolic disorders, markers of inflammation, cardiovascular diseases—particularly heart attacks and strokes—as well as premature death. The authors describe the new findings as further evidence in a broader public health debate, in which they argue that the food industry’s priorities may conflict with the needs of the U.S. population. They compare the situation to tobacco use and point out that, as early as the middle of the last century, evidence regarding the dangers of cigarette smoking was accumulating; however, it took decades for the body of evidence and the work of forward-thinking health authorities to lead to policy measures aimed at reducing smoking.

The researchers believe that ultra-processed foods could follow a similar trajectory. “Reducing the consumption of UPFs is a complex public health challenge, especially given the widespread prevalence and easy availability of these products,” said co-author Timothy De Ver Dye, Ph.D., professor and chair of the Department of Population Health at FAU. “Healthcare providers should recognize that many patients face barriers to accessing healthier dietary options and affording them. Addressing these challenges requires efforts that go beyond individual decisions to support better access to nutritious, minimally processed foods.”

Prostate cancer remains a major health issue both in the United States and worldwide. The American Cancer Society estimates that in 2026, more than 333,000 men in the U.S. will be diagnosed with prostate cancer and that more than 36,000 will die from the disease. Worldwide, nearly 1.5 million men were diagnosed with prostate cancer in 2022, according to the International Agency for Research on Cancer. Nearly 400,000 men died from the disease that year

How Prostate Cancer Evolves to Evade Treatment

Some resistant prostate tumors survive by activating alternative biological signaling pathways that reshape the identity of their cells. In the process, the cancer cells lose some of their glandular characteristics and assume other cellular identities. Scientists refer to this process as transdifferentiation. In a new study published in JCI Insight, researchers at the University of Michigan identified two signaling pathways that could be targeted simultaneously to treat prostate tumors that have undergone this transformation. The researchers believe that this strategy could ultimately have implications beyond prostate cancer. They hope that similar approaches could also be effective against other types of cancer that undergo transdifferentiation, including lung and pancreatic cancer.

Previous research had linked the loss of two genes, TP53 and RB1, to transdifferentiation in prostate cancer. However, it remained unclear exactly why the loss of these genes causes such a dramatic change in the identity of the tumor cells. To investigate this, the researchers examined several prostate cancer cell lines and determined which cellular signaling pathways changed when TP53 and RB1 were absent. “We found that this transition has two aspects: the loss of glandular genes and the activation of cellular programs that cause the identity to shift toward that of stem cells,” said Dr. Joshi Alumkal, professor of internal medicine—hematology/oncology and a member of the Rogel Cancer Center.

Two Classes of Drugs Target Different Aspects of Cancer Transformation

The research team had previously shown that so-called BET bromodomain inhibitors can disrupt signaling pathways that allow prostate cancer cells to activate alternative identity programs. However, these drugs alone could not permanently halt the progression of the cancer. In the new experiments, the researchers again found that BET bromodomain inhibitors slowed the growth of prostate cancer cell lines. However, the drugs did not kill the cancer cells. This prompted the team to investigate a second group of drugs known as DNA methyltransferase, or DNMT, inhibitors.

DNMT inhibitors can reactivate silenced genes. In this case, the researchers were particularly interested in restoring glandular genes, which are often lost when prostate cancer cells change their identity. These inhibitors have already received FDA approval for other conditions, including blood cancer.

Drug Combination Slows the Growth of Prostate Tumors

The researchers then combined BET bromodomain inhibitors with DNMT inhibitors. The combined use of the two types of drugs suppressed the growth of prostate cancer cell lines more effectively than either drug alone. The researchers observed a similar effect in prostate tumors implanted in mice.

“When we used both drugs, we were able to reverse a significant portion of the changes in gene expression occurring in the tumors, which is encouraging,” said Dr. Will Storck, a research laboratory specialist in the Alumkal Lab. It is also promising that they observed a significant reduction in tumor growth even at doses well below the recommended dose, and that this drug combination was well tolerated by the mice. The results suggest that it may be more effective to specifically target both aspects of cancer cell transformation than to block just one of them. One drug interferes with programs that promote an alternative cellular identity, while the other helps restore lost gland-related gene activity.

Identifying the Patients Most Likely to Benefit

The researchers now want to determine which genes are primarily responsible for the antitumor effects observed in the experiments. They also aim to identify biomarkers that can be used to determine which patients are most likely to benefit from the drug combination. Another important question is whether the treatment could prevent transdifferentiation before it occurs, rather than attempting to treat tumors after they have already changed their identity.

Preventing transdifferentiation from occurring would be crucial for patient survival. “Distinguishing between patients whose tumors will never undergo this transition and those in whom this may be the case would be helpful in deploying this treatment effectively and at an early stage.” The team hopes to develop clinical trials to determine whether the combination of BET bromodomain and DNMT inhibitors could benefit patients with transdifferentiated prostate cancer. The researchers are also interested in investigating whether the same dual-agent approach could be effective against other types of cancer in which similar changes in cellular identity occur.