Pathologic Signaling and Disease Implications of Insulin-like Growth Factor Binding Proteins in Cancer, Cardiovascular Disease, and Fibrosis

The insulin-like growth factor binding protein (IGFBP) family consists of seven members, which are known for their roles in regulating canonical insulin-like growth factor (IGF) signaling and, more recently, a variety of non-canonical signaling pathways. This review will explore shared pathologic mechanisms amongst the IGFBP family members in diseases like cancer and fibrosis which reveal the unique and redundant properties of this critical family of proteins and provides unique insight into how their regulation is not only relevant to cell metabolism, but also plays an emerging role in diverse processes including immunity, TGF-β signaling, hypoxia and angiogenesis, and senescence. Moreover, these molecules have shown promise both as biomarkers and therapeutics, and a deeper understanding of this system is needed to appreciate how leveraging their regulation may be able to ameliorate diverse organ pathologies.