Metformin, a diabetes drug, has shown promise in countering the metabolic strain of hormone therapy in prostate cancer patients, even when physical activity is limited. This study, led by physician-scientists at Sylvester Comprehensive Cancer Center, reveals that metformin raises levels of a molecule called N-lactoyl-phenylalanine (Lac-Phe), which is typically associated with intense exercise. The findings offer a fascinating insight into the internal pathways that underlie exercise's metabolic benefits and how these pathways might still be engaged when movement is limited.
The research, published in EMBO Molecular Medicine, highlights the importance of transdisciplinary collaboration, bringing together laboratory science, metabolic biology, and clinical investigation. Marijo Bilusic, M.D., Ph.D., a Sylvester researcher and first author, emphasizes the significance of linking molecular signals to real patient data. While metformin does not replace physical activity, it provides a clearer understanding of how a widely used drug may support metabolic health during prostate cancer treatment.
Lac-Phe, a molecule produced under metabolic demand, spikes after intense exercise, coinciding with shifts in energy use and appetite regulation. The study found that higher Lac-Phe levels were associated with reduced appetite and improved weight control, even in the absence of physical activity. This overlap raised an important question: could a pathway typically associated with exercise be activated pharmacologically in patients whose treatments limit movement?
The Sylvester team focused on prostate cancer, where hormone-based therapies disrupt metabolism, leading to weight gain, insulin resistance, and cardiovascular risk. Notably, Lac-Phe levels in patients treated with metformin approximated those reported after strenuous exercise, even without physical activity. This effect persisted after hormone therapy began, suggesting a potential therapeutic benefit for patients with limited physical activity.
However, it's crucial to note that higher Lac-Phe levels were not associated with an anti-tumor response to metformin. The metabolite did not correlate with changes in prostate-specific antigen (PSA), a standard marker of prostate cancer. This distinction is essential, as it suggests that Lac-Phe reflects the body's management of energy, weight, and metabolic strain during treatment, rather than a direct effect on tumor growth.
The study's findings have broader implications, as they suggest Lac-Phe may be a valuable signal for understanding how metformin affects metabolism in prostate cancer patients. David B. Lombard, M.D., Ph.D., a Sylvester researcher, highlights the importance of metabolism in cellular processes and the potential of Lac-Phe as an informative signal in this context.
In conclusion, this research offers a promising perspective on how metformin may support metabolic health during prostate cancer care, even when physical activity is limited. By understanding the metabolic effects of treatments, healthcare professionals can better support patients' overall well-being and quality of life throughout their cancer journey.
