Sildenafil in Combination Therapy against Cancer: A Literature Review

The concepts of drug repurposing and Sildenafil or blue pill are tightly linked over the years. Indeed, in addition to its initial clinical application as an anti-hypertensive drug in the pulmonary system, Sildenafil is also known for its beneficial effects in erectile dysfunction. Moreover, evidence has been accumulated to support its value in anti-cancer therapy, either alone or in combination with other clinically efficient chemotherapy drugs. In this review, we focused on the old and recent in vitro and in vivo studies demonstrating the cellular and molecular rationale for the application of Sildenafil in combination therapy in various types of cancer. We emphasized on the different molecular targets as well as the different signaling pathways involved in cancer cells. The pro-apoptotic effect of Sildenafil through nitric oxide (NO)/ phosphodiesterase type 5 (PDE5)-dependent manner seems to be one of the most common mechanisms. However, the activation of autophagy, as well as the modulation of the anti-tumor immunity, constitutes the other pathways triggered by Sildenafil. Overall, the studies converged to reveal the complexity of the anti-cancer potential of Sildenafil. Thus, through our review, we aimed to present an updated and simplified picture of such repurposing of Sildenafil in the field of oncology.