Phosphodiesterase function and endocrine cells: links to human disease and roles in tumor development and treatment

Phosphodiesterases (PDEs) are enzymes that regulate the intracellular levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate, and, consequently, exhibit a central role in multiple cellular functions. The pharmacological exploitation of the ability of PDEs to regulate specific pathways has led to the discovery of drugs with selective action against specific PDE isoforms. Considerable attention has been given to the development of selective PDE inhibitors, especially after the therapeutic success of PDE5 inhibitors in the treatment of erectile dysfunction. Several associations between PDE genes and genetic diseases have been described, and more recently PDE11A and PDE8B have been implicated in predisposition to tumor formation. This review focuses on the possible function of PDEs in a variety of tumors, primarily in endocrine glands, both in tumor predisposition and as potential therapeutic targets.

► Phosphodiesterases (PDEs) regulate intracellular levels of cAMP and cGMP.
► These second messengers are involved in cell differentiation and proliferation.
► Involvement of PDEs in tumor predisposition is not an unexpected finding.
► Recently, a role for PDE11A and PDE8B in tumor predisposition has been described.
► This review focuses on the possible function of PDEs in endocrine and other tumors.