Background: Phosphodiesterase-5 (PDE5) inhibitors demonstrate off-label
anticancer properties, acting through a variety of mechanisms that ultimately reduce tumor
Method: Combining PDE5 inhibitors with other anti-oncotic agents further enhances
their effectiveness against tumors. Mechanistically, PDE5 inhibitors have been shown to
inhibit ATP binding cassette (ABC) transporter protein activity, potentiate reactive oxygen
species (ROS) activity, decrease FADD-like IL-1β-converting enzyme (FLICE)-
inhibitory protein (c-FLIP) expression, increase blood-brain tumor barrier (BTB) permeability,
and, when administered as a combination therapy, sensitize tumors to platinum.
Conclusion: This review offers insights into the various mechanisms by which PDE5
inhibitors exert their antineoplastic actions.