Human epidermal growth factor receptor 2, Insulin-like growth factor 1 receptor, and Insulin-like growth factor-binding protein 2 (HER2/IGF1R/IGFBP-2)

The HER2/IGF1R/IGFBP-2 signaling axis is a complex molecular network that plays a pivotal role in the progression and therapeutic resistance of various cancers, most notably HER2-positive breast cancer [1, 6]. HER2 (Human Epidermal Growth Factor Receptor 2) and IGF1R (Insulin-like Growth Factor 1 Receptor) are receptor tyrosine kinases that engage in significant crosstalk and can form heterodimers, which allows cancer cells to bypass the inhibitory effects of HER2-targeted therapies like trastuzumab [4, 15]. IGFBP-2 (Insulin-like Growth Factor-Binding Protein 2) further modulates this axis by regulating the bioavailability of IGF ligands and interacting with other signaling molecules like PTEN and integrins to promote cell survival and invasion [2, 11]. High expression of these components is often associated with poor clinical outcomes and the development of resistance to standard-of-care treatments [7, 10]. Consequently, therapeutic strategies focusing on the dual or triple inhibition of this axis are being explored to enhance treatment efficacy and overcome drug resistance in oncology [5, 9].

Other names

ErbB2/IGF1R/IGFBP2 axisIGF-1/HER2 crosstalk pathwayHER2-IGF1R-IGFBP2 signaling network

Simultaneous inhibition of HER2 and IGF1R signaling pathways to overcome therapeutic resistance and suppress tumor growth and invasion [4, 6, 9].