FASN as a Therapeutic Target in Genitourinary Diseases: From Cancers to Benign Disorders.

Abstract

Fatty acid synthase (FASN) is the key catalytic enzyme of de novo lipogenesis and is increasingly recognized as a driver of metabolic reprogramming in genitourinary disease. In both malignant and non-malignant settings, aberrant FASN expression and activity are associated with tumor growth, metastatic spread, drug resistance, renal lipotoxicity, fibrosis, and immune remodeling. However, current evidence remains scattered across organ-specific studies, and a focused synthesis across the genitourinary system is still lacking. This review summarizes the expression patterns, upstream regulators, downstream effects, and translational relevance of FASN in major genitourinary organs, with emphasis on the bladder, kidney, prostate, cervix, and ovary, as well as selected benign disorders. We also review current therapeutic strategies, including direct FASN inhibition, modulation of upstream lipogenic pathways, nanodelivery approaches, and rational combination regimens with chemotherapy, endocrine therapy, or immunotherapy. Available data support FASN as a shared metabolic node linking lipid reprogramming to both malignant progression and organ injury. In bladder, renal, prostate, and cervical cancers, FASN contributes to proliferation, invasion, metastasis, and treatment resistance. In renal and reproductive disorders, it is also involved in lipid deposition, inflammation, fibrosis, and ovulatory dysfunction. Despite promising preclinical findings, major challenges remain, including limited evidence in benign disease, marked mechanistic heterogeneity across organs, and insufficient clinical validation of biomarkers and targeted agents. A more integrated understanding of FASN may improve biomarker development and support metabolism-based precision therapy in genitourinary disease.