Insulin-like growth factor-neutralizing antibodies for cancer therapy

The insulin-like growth factor (IGF) axis is crucial for regulating cell growth, survival, and differentiation. While therapies targeting the IGF-1 receptor (IGF-1R) have shown limited clinical success as single agents, the abnormal expression of its ligands, IGF-I and IGF-II, has been shown to contribute significantly to resistance against IGF-1R-targeted treatments. This review explores recent advancements in neutralizing antibodies against IGF-I and/or IGF-II, including monoclonal antibody, bispecific antibodies and engineered antibody domains. These approaches have demonstrated promising therapeutic potential in preclinical cancer models and are currently being evaluated in early clinical trials. Furthermore, we address the rationale for future combination strategies to overcome treatment resistance.