Abstract
Selective phosphodiesterase 5 inhibitors, including sildenafil, tadalafil and vardenafil, are widely-used in the treatment of erectile dysfunction and pulmonary arterial hypertension. They are also well-known as examples of successful drug repurposing in that they were initially developed for angina and only later developed for erectile dysfunction. However, these drugs may also be effective cancer treatments. A range of evidentiary sources are assessed in this paper and the case made that there is pre-clinical and clinical evidence that these drugs may offer clinical benefit in a range of cancers. In particular, evidence is presented that these drugs have potent immunomodulatory activity that warrants clinical study in combination with check-point inhibition.
Highlights
Phosphodiesterase (PDE) inhibitors are drugs which block the activity of one or more of the 12 PDE isoforms, thereby modulating intracellular levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate
This review focuses on the anti-cancer properties of the partially selective PDE5 inhibitors, sildenafil, tadalafil and vardenafil
Pernkopf et al [16] later showed that sildenafil, vardenafil and tadalafil had no effect on the proliferation of prostate cancer cell lines in vitro, even at high concentrations (1 mg/ml)
Summary
Phosphodiesterase (PDE) inhibitors are drugs which block the activity of one or more of the 12 PDE isoforms, thereby modulating intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Pernkopf et al [16] later showed that sildenafil, vardenafil and tadalafil had no effect on the proliferation of prostate cancer cell lines in vitro, even at high concentrations (1 mg/ml). The combination of doxorubicin and sildenafil (at an oral dose of 10 mg/kg) in BALB/c mice bearing human PC-3 prostate cancer xenografts significantly (P < 0.05) reduced tumour growth compared to controls.
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