IGFBP4 and neoplasm: Initial studies of IGFBP-4 gene therapy administered in colorectal cancer xenograft models resulted in a decrease in tumor micro-vessel counts and an increase in apoptosis.[25] Most recently, Zhu et al. have shown that IGFBP-4 has IGF-independent activity as a cardiogenic growth factor, and data suggest that it acts as a competitive inhibitor of the canonical Wnt signaling pathway [26].