Vascular endothelial growth factor and insulin-like growth factor 1 pathways (VEGF/IGF-1)

The Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor 1 (IGF-1) pathways are two interconnected signaling systems that play critical roles in physiological development and the progression of various diseases, including cancer and ocular disorders. VEGF is the primary mediator of angiogenesis and vascular permeability, signaling through its receptors (VEGFR-1, -2, and -3) to promote endothelial cell survival and migration (Ferrara, 2004, Nature). IGF-1, acting through the IGF-1 receptor (IGF-1R), is a potent growth factor that regulates cell proliferation and metabolism, and it has been shown to act as a permissive factor for VEGF-induced neovascularization (Smith et al., 1999, Science). In conditions like diabetic retinopathy and age-related macular degeneration, elevated levels of both VEGF and IGF-1 contribute to pathological vessel growth and vision loss (Hellstrom et al., 2001, PNAS). Furthermore, the IGF-1 pathway can provide a bypass mechanism for tumor cells to survive anti-VEGF therapy, leading to drug resistance (Gualberto et al., 2009, The Lancet Oncology). Consequently, therapeutic strategies targeting both pathways are being investigated to provide more comprehensive inhibition of disease progression and improve patient outcomes.

Other names

VEGF and IGF-1 signaling axisVEGF-IGF-1 crosstalkVEGF/IGF-1 pathway

Simultaneous or sequential inhibition of VEGF-mediated endothelial cell activation and IGF-1-mediated cell survival and proliferation to suppress pathological angiogenesis and tumor growth.