Targeting Polyamines and Inflammation for Cancer Prevention

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.

Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back

“…The polyamine transporter (PAT) is frequently upregulated in many tumor types and is crucial for importing exogenous polyamines [95]. The imaginal disc epithelium of Drosophila has been successfully used to screen PAT-selective molecules [96].…”

The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells

“…Increased polyamine synthesis is associated with inflammation 78 ; thus, polyamines accumulate in infected tissues 79 . More than 60 years ago, it was reported that spermine levels increase at sites of mycobacterial infection and that spermine possesses tuberculostatic activity 80 .…”

Metabolism Links Bacterial Biofilms and Colon Carcinogenesis

“…Treatment of colon cancer models and clinical trials with polyamine-metabolism inhibitors have resulted in ambiguous findings (Babbar and Gerner, 2011), however targeting both polyamine production and biofilm interactions could prove to be a more successful strategy.…”