Protein Tyrosine Phosphatases in Cancer: From Oncogenic Drivers to Therapeutic Targets.

Protein tyrosyl phosphorylation is a dynamic reversible regulatory process that is essential for virtually all aspects of cellular function. The dysregulation of protein tyrosyl phosphorylation is one of the main causes of human diseases such as cancer, diabetes, autoimmune disorders, and neurological diseases. Protein tyrosine kinases (PTKs) have paved the way towards defining the significance of protein tyrosyl phosphorylation in human health and disease. However, homeostatic control of protein tyrosyl phosphorylation is also regulated by protein tyrosine phosphatases (PTPs). The actions of PTPs are diverse functioning to both positively and negatively regulate signaling pathways through specific substrate dephosphorylation. PTKs are now matured targets with numerous drugs that have been developed for the treatment of human diseases such as cancer and immunological disorders. In contrast, PTPs are relatively in their infancy as compared with their PTK counterparts with regard to drug development for the treatment of human diseases. However, mounting evidence supports the view that PTPs are not only valid targets but are indeed targetable. This review focuses primarily on the roles of PTPs as oncogenic drivers and therapeutic targets in cancer, while briefly noting their broader relevance to other diseases in which tyrosyl phosphorylation is dysregulated. This review will highlight recent developments in the PTP field, with an emphasis on cancer, which provide support for the emergence of PTPs as therapeutic targets, and will also briefly touch upon their relevance to related conditions such as obesity, type II diabetes and rare diseases.