Study: Targeting Metabolism may Improve Patient well-being During Prostate Cancer Treatment

A recent study suggests that metformin, an orally bioavailable biguanide commonly used to treat diabetes (T2DM), is among the most frequently prescribed insulin-sensitizing drugs worldwide and may replicate some of the key biological effects of exercise in men with prostate cancer. [1][2]

Researchers found that metformin raises levels of a molecule linked to energy regulation and weight management—even when patients are not physically active. This discovery points to metformin’s potential to help manage the metabolic challenges posed by hormone therapy, a treatment that often leaves patients too fatigued for regular exercise.

The research was conducted by physician-scientists at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, and published in EMBO Molecular Medicine.[2]

Supporting health during treatment
Exercise is well-established as a way to support health during cancer treatment, improving weight control, blood sugar, and cardiovascular health. However, fatigue, side effects of hormone therapy, pain, or advanced disease can make regular exercise difficult for many cancer patients—precisely when metabolic health is most at risk.

This dilemma led researchers to ask: if exercise works through specific biological pathways, can those pathways be activated in other ways? According to their findings, the answer is yes. The team discovered that metformin increases blood levels of a naturally occurring molecule involved in the body’s energy and weight regulation in prostate cancer patients.

Importantly, the study does not suggest that metformin can replace the broader benefits of physical activity. Instead, it highlights how certain internal pathways associated with exercise’s metabolic effects might be engaged by medication when patients are unable to stay active.

“This study shows what’s possible when laboratory science, metabolic biology, and clinical research come together,” said Marijo Bilusic, MD, Ph.D,. first author and professor of medicine at the Miller School. “By collaborating across disciplines, we connected a well-defined molecular signal to actual patient outcomes. While this isn’t a new cancer biomarker, it does clarify how a common drug may support metabolic health during prostate cancer treatment,” Bilusic added

N-lactoyl-phenylalanine
The molecule at the center of this research is N-lactoyl-phenylalanine (Lac-Phe)*. Lac-Phe is produced during metabolic stress when lactate (produced during exertion) combines with phenylalanine, an amino acid. Scientists first became interested in Lac-Phe because its levels rise after intense exercise and have been linked to reduced appetite and improved weight control—benefits often associated with regular physical activity.

Interestingly, Lac-Phe levels also increased in people taking metformin, even without exercise. This overlap prompted the team to investigate whether a pathway usually triggered by exercise could be activated by medication in patients who cannot be physically active due to their treatment.

Focusing on prostate cancer, where hormone therapy often disrupts metabolism and raises risks for weight gain and cardiovascular issues, the researchers found that metformin-induced Lac-Phe levels matched those seen after strenuous exercise. This effect persisted even after hormone therapy began, and was observed in patients who were not exercising at the time their blood was drawn.

“For patients whose treatments limit physical activity, seeing a metabolic signal that mirrors intense exercise is particularly meaningful,” said Dr. Bilusic.

Energy and metabolic stress
Notably, higher Lac-Phe levels were not associated with anti-cancer effects, including changes in prostate-specific antigen (PSA) levels. Instead, Lac-Phe appears to reflect the body’s management of energy and metabolic stress during treatment. The findings held true across clinical settings and among patients receiving other metabolic therapies, suggesting a broader metabolic response.

“Cancer treatment affects the body well beyond the tumor,” said Dr. Priyamvada Rai, co-leader of the Tumor Biology Program at the Miller School. “Supporting metabolic health can improve how patients tolerate therapy and their overall well-being, even if it doesn’t directly impact tumor growth.”

The study also found that while metformin raises the stress hormone GDF-15, only Lac-Phe levels were closely tied to weight changes, suggesting multiple metabolic pathways are involved.

“These results suggest Lac-Phe could be a valuable indicator of how metformin influences metabolism in prostate cancer patients,” said Dr. David B. Lombard, co-leader of the Cancer Epigenetics Program.

Overall, the study provides new insight into how a widely used diabetes drug may benefit metabolic health during prostate cancer treatment.