The role and research progress of FGF21 in breast cancer: a review

Purpose To investigate the molecular mechanisms, functional controversies, and clinical significance of Fibroblast Growth Factor 21 (FGF21) in the context of breast cancer. Methods A comprehensive literature search was conducted across databases including PubMed and CNKI to summarize recent advances regarding FGF21 in metabolic reprogramming and immune microenvironment remodeling. Results FGF21 primarily serves as a pro-tumorigenic factor in breast cancer through several key mechanisms: (1) Metabolic Reprogramming: It activates the ERK1/2-SENP2 axis to upregulate CD36, which enhances fatty acid oxidation to fuel tumor metastasis. (2) Immune Evasion: It induces CD8 + T cell exhaustion by persistently activating intracellular cholesterol synthesis pathways. (3) Anti-apoptosis: It enhances chemoresistance by activating signaling pathways such as STAT3. Clinically, elevated FGF21 levels are significantly correlated with disease progression and poor prognosis, particularly in patients with metabolic comorbidities. Conclusion FGF21 acts as a pivotal bridge connecting systemic metabolism with local tumor behavior. Future research should focus on developing precision intervention strategies that preserve its systemic metabolic benefits while selectively blocking its local oncogenic effects.