Researchers at the University at Buffalo have demonstrated for the first time that intermittent fasting significantly enhances the efficacy of anti-androgen therapy in prostate cancer, according to preclinical results published in Cancer Research on August 8. The groundbreaking study reveals a novel therapeutic approach that could transform how clinicians approach prostate cancer treatment by combining dietary interventions with standard hormone therapy.
Mechanism of Enhanced Drug Sensitivity
The research team, led by Roberto Pili, MD, associate dean for cancer research and integrative oncology at the Jacobs School of Medicine and Biomedical Sciences, found that alternate-day fasting fundamentally alters the tumor microenvironment in ways that make cancer cells more vulnerable to treatment. In mouse models of prostate cancer, restricting consumption of proteins, fats, and carbohydrates through alternate-day fasting reduced androgen receptor expression and signaling, directly enhancing the antitumor activity of enzalutamide, a standard androgen receptor inhibitor.
The study revealed that alternate-day fasting reduced amino acid levels and global protein synthesis within prostate cancer tumors, creating metabolic stress that made tumors more sensitive to the drug. This benefit was consistently demonstrated across multiple mouse models of prostate cancer, suggesting the approach may have broad applicability.
Dietary Impact on Cancer Biology
The research builds on growing evidence linking Western dietary patterns to cancer progression. As Pili explains, "Diet can have a significant impact on the biology of prostate cancer and dietary interventions should be seen as an adjuvant tool." The typical Western diet, with its heavy animal fat and protein content, has been linked to increased cancer incidence and poor prognosis, while caloric restriction has emerged as a potential strategy for reducing cancer incidence and delaying progression.
Proteins, carbohydrates, and fats are necessary for the uncontrolled growth of cancer cells, and caloric restriction has been shown in preclinical models to reduce circulating growth factors and hormones that promote cancer development.
Clinical Translation Underway
Building on these promising preclinical findings, Pili is actively recruiting patients for clinical trials to test the approach in humans. The trials include studies of restricted eating in prostate cancer patients receiving hormone therapy, as well as investigations of plant-based diets combined with caloric restriction for cancer patients undergoing chemotherapy.
"The goal is to complete the ongoing clinical trials and to learn more about the impact of dietary restrictions on the biology of prostate cancer and other hormone-driven tumors, such as breast cancer," Pili states.
Collaborative Research Effort
The study represents a collaborative effort involving researchers from multiple institutions, including co-corresponding author Kirk A. Staschke, PhD, from the Indiana University Melvin and Bren Simon Comprehensive Cancer Center and the IU School of Medicine. Additional co-authors contributed from the Indiana University School of Medicine, Roswell Park Comprehensive Cancer Center, the University of Sydney, and Royal Prince Alfred Hospital in Sydney.
The research received substantial funding support from the National Institutes of Health, the Showalter Trust, the Prostate Cancer Foundation, the Department of Defense, Indiana University, the American Cancer Society, the Lilly Endowment Inc., the Bakewell Foundation, and the Australian Youth and Health Foundation, reflecting the broad scientific interest in this therapeutic approach.
