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PDE5 Inhibitors Offer Novel Mechanisms in Combination and Solo Cancer Therapy

[ Vol. 13 , Issue. 2 ]

Author(s):

Robert W. Lyday , Abigail M. Etters, Chris Kim, Fernando Magana, Gabriel M. Pontipiedra, Naveen K.M. Singh and Samuel Kadavakollu *   Pages 107 - 119 ( 13 )

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®.

Affiliation:

Department of Biomedical Sciences, Burrell College of Osteopathic Medicine, Las Cruces, NM 88001, Department of Biomedical Sciences, Burrell College of Osteopathic Medicine, Las Cruces, NM 88001, Department of Biomedical Sciences, Burrell College of Osteopathic Medicine, Las Cruces, NM 88001, Department of Biomedical Sciences, Burrell College of Osteopathic Medicine, Las Cruces, NM 88001, Department of Biomedical Sciences, Burrell College of Osteopathic Medicine, Las Cruces, NM 88001, Department of Pharmacology & Radiation Oncology, Simmons Comprehensive Cancer Center (SCCC), UT Southwestern Medical Center (UTSW), Dallas, TX 75390, Department of Biomedical Sciences, Burrell College of Osteopathic Medicine, Las Cruces, NM 88001

Graphical Abstract:



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