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Polyamines and cancer: implications for chemotherapy and chemoprevention

Published online by Cambridge University Press:  22 February 2013

Shannon L. Nowotarski ,
Patrick M. Woster  and
Robert A. Casero Jr
Shannon L. Nowotarski
Affiliation:
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA
Patrick M. Woster
Affiliation:
Department of Drug Discovery and Biomedical Sciences, The Medical University of South Carolina, Charleston, SC 29425, USA
Robert A. Casero Jr*
Affiliation:
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA
*
*Corresponding author: Robert A. Casero, The Johns Hopkins University School of Medicine, Bunting/Blaustein Cancer Research Building 1, 1650 Orleans Street – Room 551, Baltimore, MD 21287, USA. E-mail: rcasero@jhmi.edu
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Abstract

Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes, and a poorly characterised transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate and skin cancers, and altered levels of rate-limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway-specific drugs and ongoing clinical trials targeting polyamine biosynthesis.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 15 , 2013 , e3
Copyright
Copyright © Cambridge University Press 2013 

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References

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Further reading, resources and contacts

Here are journal review articles that were not featured above which provide useful information on the topic of polyamines.

Pegg, A.E. (2008) Spermidine/spermine-N(1)-acetyltransferase: a key metabolic regulator. American Journal of Physiology. Endocrinology and Metabolism 294, E995-E1010.

Wallace, H.M. and Niiranen, K. (2007) Polyamine analogues – an update. Amino Acids 33, 261-265.

Wallace, H.M. (2009) The polyamines: past, present and future. Essays in Biochemistry 46, 1-9.

Wang, Y. and Casero, R.A. (2006) Mammalian polyamine catabolism: a therapeutic target, a pathological problem, or both?. Journal of Biochemistry (Tokyo) 139, 17-25.

Seiler, N. (2003) Thirty years of polyamine-related approaches to cancer therapy. Retrospect and prospect. Part 2. Structural analogues and derivatives. Current Drug Targets 4, 565-585.

Here are textbooks that were not cited in the above article. These provide useful information concerning polyamines, methods for studying the polyamine pathway and the use of polyamines in drug discovery.

Cohen, S.S. (1998) A Guide to the Polyamines, Oxford University Press, New York, USA.

Pegg, A.E. and Casero, R.A. (2011) Polyamines: Methods and Protocols, Humana Press/Springer Science + Business Media, New York, USA.

Wallace, H.M. (2009) The Polyamines: Small Molecules in the Omics Era, Portland Press, London, UK.

Wang, J.Y. and Casero, R.A. (2006) Polyamine Cell Signaling: Physiology, Pharmacology, and Cancer Research, Humana Press, New Jersey, USA.

Woster, P.M. and Casero, R.A. (2011) Polyamines Drug Discovery, Royal Chemical Society Publishing, London, UK.