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Targeting Polyamines and Inflammation for Cancer Prevention

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Clinical Cancer Prevention

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 188))

Abstract

Increased polyamine synthesis and inflammation have long been associated with intraepithelial neoplasia, which are risk factors for cancer development in humans. Targeting polyamine metabolism (by use of polyamine synthesis inhibitors or polyamine catabolism activators) and inflammation (by use of nonsteroidal anti-inflammatory drugs) has been studied for many cancers, including colon, prostate, and skin. Genetic epidemiology results indicate that a genetic variant associated with the expression of a polyamine biosynthetic gene is associated with risk of colon and prostate cancers. A clinical trial of difluoromethylornithine (DFMO), a selective inhibitor of polyamine synthesis, showed that the 1 year treatment duration reduced prostate volume and serum prostate-specific antigen doubling time in men with a family history of prostate cancer. A second, clinical trial of DFMO in combination with sulindac, a NSAID in patients with prior colon polyps found that the 3-year treatment was associated with a 70% reduction of all, and over a 90% reduction of advanced and/or multiple metachronous colon adenomas. In this chapter, we discuss that similar combination prevention strategies of targeting polyamines and inflammation can be effective in reducing risk factors associated with the development of human cancers.

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Abbreviations

APAO:

FAD-dependent polyamine oxidase

DFMO:

d,l-α-difluoromethylornithine

NSAID:

Non-steroidal anti-inflammatory drug

ODC:

Ornithine decarboxylase

SAMDC:

S-adenosylmethionine Decarboxylase

SAT1:

Spermidine/Spermine N1-Acetyltransferase

APC:

Adenomatous polyposis coli

SMO:

Spermine oxidase

OAZ:

Ornithine decarboxylase antizyme

NOS:

Nitric oxide synthases

PPAR:

Gamma: Peroxisomal proliferator activated receptor γ

COX-2:

Cyclooxygenase-2

TNFalpha:

Tumor necrosis factor-α

BCC:

Basal cell carcinoma

FAP:

Familial adenomatous polyposis

PIA:

Proliferative inflammatory atrophy

PIN:

Prostatic intraepithelial neoplasia

PSA:

Prostate specific antigen

NMSC:

Nonmelanoma skin cancers

SCC:

Squamous cell carcinoma

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Acknowledgments

This work was supported in part by grants from the USPHS National Institutes of Health CA95060 and CA123065.

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  1. Research and Development, Osmetech Molecular Diagnostic, 757 S Raymond Avenue, Pasadena, CA, 91105, USA

    Naveen Babbar

  2. Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ, 85724, USA

    Eugene W. Gerner

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  1. Prävention (ZeTuP), Zentrum für Tumordiagnostik und, Rorschacherstr. 150, St. Gallen, 9006, Switzerland

    Hans-Jörg Senn

  2. Prävention (ZeTuP), Zentrum für Tumordiagnostik und, Rorschacherstr. 150, St. Gallen, 9006, Switzerland

    Florian Otto

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The views and opinions presented by Babbar, N. are solely the author’s and do not necessarily reflect the views and opinions of his employer, Osmetech Molecular Diagnostics.

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Babbar, N., Gerner, E.W. (2010). Targeting Polyamines and Inflammation for Cancer Prevention. In: Senn, HJ., Otto, F. (eds) Clinical Cancer Prevention. Recent Results in Cancer Research, vol 188. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-10858-7_4

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