Research
Research in the Frigo Laboratory
The Frigo Lab¡¯s research bridges discovery science with translational innovation, targeting metabolic and signaling pathways that define prostate cancer aggressiveness and treatment resistance. Through a systems-level understanding of tumor biology ¡ª spanning metabolomics, diet-microenvironment interactions, genetics, different types of cell death and endocrinology ¡ª we aim to develop smarter therapeutic strategies and imaging tools to improve outcomes for patients with advanced prostate cancer.
We have three research focus areas:
1. Metabolic Vulnerabilities as Therapeutic Entry Points
One of our lab¡¯s major goals is to understand how prostate cancer cells adapt metabolically to support growth and evade therapy. Our recent work has highlighted lipid metabolism, particularly the mobilization and breakdown of lipid droplets, as a critical process in advanced disease. We demonstrated that the enzyme adipose triglyceride lipase (ATGL) plays an essential role in promoting prostate cancer progression by enabling metabolic plasticity. Inhibiting ATGL disrupts lipid homeostasis and forces a compensatory glycolytic shift, opening a window for therapeutic synergy. Targeting this shift with dual metabolic inhibition significantly impairs tumor growth in preclinical animal models, nominating a novel therapeutic approach.
2. Linking Diet, Tumor Genetics and the Microenvironment
Beyond tumor-intrinsic pathways, we are investigating how extrinsic factors such as diet interact with tumor genetics to shape cancer metabolism and the tumor microenvironment. Collaborating with clinical and computational teams, we have been studying how systemic metabolism (e.g., obesity, diet) and body composition exacerbate certain subtypes of cancer by promoting glycolysis, angiogenesis and immunosuppressive remodeling. These findings are supported by data from large clinical cohorts and suggest that secondary effects of diets and obesity can influence disease aggressiveness and treatment response most when particular somatic tumor alterations are present.
3. Emerging Targets Beyond the Usual Suspects
While androgen receptor (AR) signaling remains the major driver of prostate cancer and is thus the major therapeutic target for almost all stages of advanced disease, our lab is exploring broader signaling and metabolic vulnerabilities. One such area is ferroptosis, a form of iron- and lipid-dependent cell death. Our is uncovering subsets of therapy-resistant prostate cancers that are highly sensitive to ferroptosis inducers, providing a potential avenue to overcome resistance mechanisms. We are also exploring novel imaging markers and drug targets related to oxidative lipid stress and related defense pathways that could be used as biomarkers of treatment response and, in future, possibly guide patient selection.