[12-16] IGFBP-3, the most abundant IGFBP in circulation, is expressed in several cancers and was recently shown to exert IGF-independent inhibitory activity on angiogenesis in vivo.[17,18] IGFBP-3 has also been shown to be a p53-response gene that induces apoptosis in an IGF-independent manner. This evidence concerns the gene IGF1 and cancer.