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Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Review Article

PDE5 Inhibitors Offer Novel Mechanisms in Combination and Solo Cancer Therapy

Author(s): Robert W. Lyday , Abigail M. Etters, Chris Kim, Fernando Magana, Gabriel M. Pontipiedra, Naveen K.M. Singh and Samuel Kadavakollu *

Volume 13, Issue 2, 2017

Page: [107 - 119] Pages: 13

DOI: 10.2174/1573394713666170731152749

Price: $65

Abstract

Background: Phosphodiesterase-5 (PDE5) inhibitors demonstrate off-label anticancer properties, acting through a variety of mechanisms that ultimately reduce tumor proliferation.

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.

Keywords: ABC transporter, anticancer therapy, antineoplastic agents, phosphodiesterase inhibitors, reactive oxygen species, sildenafil, Viagra®.

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