The IGF and IGF1R signaling axis in tumor metabolic reprogramming and immune microenvironment remodeling

Abstract The insulin-like growth factor/insulin-like growth factor 1 receptor (IGF/IGF-1R) signaling pathway plays a pivotal role in physiological processes such as cell growth, differentiation, and apoptosis, and its aberrant activation is closely associated with tumor initiation and progression. This review systematically summarizes the molecular mechanisms of the IGF/IGF-1R signaling pathway, its role in tumor metabolic reprogramming and immune microenvironment remodeling, and targeted therapeutic strategies against this pathway, while also exploring future research directions. Through a comprehensive analysis of the available evidence, we propose that IGF/IGF-1R signaling may function as an important regulatory node within a broader metabolic–immune network in cancer. Its effects on tumor metabolism and immune regulation appear to be highly context dependent, varying according to tumor type, cellular state, nutrient availability, and the activation of parallel signaling pathways. Although substantial preclinical evidence supports interactions between IGF/IGF-1R signaling, metabolic reprogramming, and immune regulation, the strength of evidence differs across individual mechanisms, and several proposed feedback relationships remain incompletely validated. Accordingly, biomarker-guided patient selection and mechanism-based combination strategies may provide potential therapeutic opportunities, but their clinical benefit requires further prospective validation.