Prostate cancer patients taking metformin had levels of a molecule normally triggered by intense exercise that matched those seen in ultramarathon runners, according to a new study published in EMBO Molecular Medicine. It is the first time that connection has been reported.
The molecule in question is N-lactoyl-phenylalanine, or Lac-Phe. Scientists identified it as a compound released during physical activity and linked it to decreased appetite and weight control. The question driving the new research was whether a drug could produce the same effect in cancer patients who struggle to stay active during treatment.
Researchers at Sylvester Comprehensive Cancer Center analyzed blood samples from men with prostate cancer enrolled in the BIMET-1 clinical trial, along with samples from a separate group treated at a cancer center. In the core trial group, 12 patients with overweight or obesity received either standard care alone or metformin at 1,000 mg twice daily, followed by the hormone therapy drug bicalutamide. An additional 25 individuals with prostate cancer across a range of disease stages were also studied, seven of whom were taking metformin. The team measured Lac-Phe levels before and after treatment in both groups.
"In our study, we were very surprised to see that the level of Lac-Phe in our prostate cancer patients was exactly the same as the level of ultramarathoners," said first study author Marijo Bilusic, MD, PhD, a genitourinary medical oncologist at Sylvester. "This has never been reported before."
The findings carry particular relevance for men on anti-androgen therapy, a standard prostate cancer treatment known to cause weight gain and metabolic changes. Exercise is widely recommended during cancer treatment to counter those effects, but many patients are unable to maintain physical activity at therapeutic levels. Metformin did not improve traditional markers of treatment response such as PSA levels or tumor growth, but the drug was associated with better weight management in the study group.
Bilusic framed the research within a broader question about cancer metabolism. "Altered metabolism is one of the hallmarks of cancer," he said. "So, what would happen with cancer patients treated with metformin?"
S. Adam Ramin, MD, a urologic oncologist and medical director of Urology Cancer Specialists in Los Angeles who was not involved in the research, called it "an intriguing preliminary study" but said larger trials would be needed to confirm the results. The study's sample sizes were small, and the researchers themselves described it as exploratory. Metformin is already widely prescribed and inexpensive, which makes it an attractive candidate for further investigation if larger studies back the early findings.
The research team noted that the drug is not a substitute for exercise. The goal is to understand whether it can offer metabolic support to patients who cannot exercise adequately, not to replace physical activity for those who can. Bilusic's team is expected to continue investigating metformin's role in cancer metabolism as part of ongoing work at Sylvester.
