IGFBP4 and cancer: Such studies reported a decade ago where a protease resistant IGFBP-4 was designed and in vivo studies of this protease resistant IGFBP-4 [81] were explored confirming the complete resistance to IGFBP-4 protease indicating that the mutant IGFBP-4 resulted in greater growth inhibition than equivalent levels of native IGFBP-4 demonstrating a role for IGFBP-4 proteolysis in the regulation of IGF-1 action and a potential implication in cancer [81].