Cancers are an extraordinarily heterogeneous collection of diseases with distinct genetic profiles and biological features that directly influence response patterns to various treatment strategies as well as clinical outcomes. Nevertheless, our growing understanding of
cancer cell biology and
tumor progression is gradually leading towards rational, tailored medical treatments designed to destroy
cancer cells by exploiting the unique cellular pathways that distinguish them from normal healthy counterparts. Recently, inhibition of the activity of
phosphodiesterase type 5 (PDE5) is emerging as a promising approach to restore normal intracellular cyclic
guanosine monophosphate (cGMP) signalling, and thereby resulting into the activation of various downstream molecules to inhibit proliferation, motility and invasion of certain
cancer cells. In this review, we present an overview of the experimental and clinical evidences highlighting the role of PDE5 in the pathogenesis and prevention of various
malignancies. Current data are still not sufficient to draw conclusive statements for
cancer patient management, but could provide further rational for testing PDE5-targeting drugs as
anticancer agents in clinical settings.