Novel Tumor Suppressive Role of Phosphodiesterases in Prostate Cancer
Posted June 4, 2021
Qianben Wang, Ph.D., Duke University
Jiaoti Huang, M.D., Ph.D., Duke University
Steven Clinton, M.D., Ph.D., The Ohio State University
Phosphodiesterase inhibitors (PDEis) are a class of compounds utilized in the treatment of a myriad of conditions, the most common of which is erectile dysfunction. PDE5 inhibitors such as sildenafil (Viagra) are widely used by men at risk of prostate cancer, those on active surveillance, and many men following or during prostate cancer treatment to aid in the recovery of sexual function and quality of life. However, the effects of PDE5 inhibitors on the biology of prostate cancer cells have not been thoroughly investigated, and the impact of their use on prostate cancer risk or progression remains uncertain.
A team led by Drs. Qianben Wang and Jiaoti Huang at Duke University and Dr. Steven Clinton at The Ohio State University studied the effects of PDE5 inhibitors on the behavior of prostate cancer cells from patients, with grant support from an FY15 PCRP Idea Development Award - Parterning PI mechanism. The team discovered that prostate cancer cells are only mildly affected when PDE5 inhibitors are present at concentrations found in patients. Interestingly, those effects are beneficial rather than harmful, and exposure to higher doses of PDE5 inhibitors interferes with the ability of prostate cancer cells to grow, survive, and migrate. Furthermore, they examined the mechanism by which PDE5 inhibition causes these antitumor effects and found that high doses of PDE5 inhibitors strongly activate the cGMP signaling pathway in prostate cancer cells. While it is not practical to expose patients to these higher doses of PDE5 inhibitors, these studies could provide insight for the discovery of novel therapeutic targets in the cGMP pathway.
These findings strongly support the safety of continued PDE5 inhibitor use by both men at risk for prostate cancer and the current prostate cancer patient population. Additionally, these results could provide important clues for the discovery of novel therapeutic strategies that may benefit patients by not just treating their prostate cancer, but also increasing their quality of life.
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Prostate cancer cell treatment with PDE5 inhibitors, at concentrations found in patients, enhances the accumulation of the small molecule cGMP (represented in red), but does not dramatically change cell biology. Higher-dose PDE5 inhibitor treatment interferes with prostate cancer cell growth, survival and migration. Ongoing studies will investigate the target proteins (represented in green) responsible for these potentially beneficial effects.
Last updated Friday, June 4, 2021