Targeting fatty acid-binding protein 4: A therapeutic intersection of obesity and cancer via lipid metabolism

Abstract

Fatty acid-binding protein 4 (FABP4) has emerged as a multifunctional regulator in cancer biology, linking dysregulated lipid metabolism, immune modulation, and tumor progression. Initially recognized for its role in fatty acid transport and lipid homeostasis, FABP4 is now understood as a secreted adipokine that influences diverse oncogenic processes, particularly in adipose-rich tumor microenvironments. It is upregulated in various cancers and secreted by both tumor and cancer-associated fibroblasts. FABP4 facilitates lipid transfer, promotes fatty acid oxidation, and reprograms cancer cell metabolism. It also contributes to the crosstalk between tumor-associated macrophages, T-cells, and dendritic cells. FABP4 also supports epithelial–mesenchymal transition, enhances tumor cell plasticity, promotes invasion and metastasis, and has an impact on therapeutic resistance. The inhibition of FABP4 using small-molecule inhibitors or monoclonal antibodies has shown promise in restoring therapeutic sensitivity and reducing metastasis in preclinical models. FABP4 has emerged as a potential diagnostic and prognostic biomarker that predicts poor outcomes in multiple cancer types, supporting risk stratification and noninvasive diagnostics. Together, these findings place FABP4 at the intersection of tumor metabolism, immune evasion, and therapy resistance, highlighting its potential as both a biomarker and a therapeutic target in precision oncology and personalized medicine.