Targeting polyamines and inflammation for cancer prevention.
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.
Research and Development, Osmetech Molecular Diagnostic, Pasadena, CA 91105, USA. naveen.babbar@osmetech.com
Naveen
N
Babbar
Eugene W
EW
Gerner
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015317:Biogenic Polyamines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007249:Inflammation / Q000150:complications; D008297:Male; D009369:Neoplasms / Q000209:etiology / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000209:etiology / Q000517:prevention & control; D012307:Risk Factors
D000893:Anti-Inflammatory Agents; D015317:Biogenic Polyamines
Lancet. 2001 Feb 17;357(9255):539-45
11229684
Biochem Biophys Res Commun. 2001 Feb 2;280(4):1042-7
11162632
Circulation. 2006 Sep 5;114(10):1028-35
16943394
Life Sci. 1992;50(19):1417-24
1573975
Curr Opin Pharmacol. 2009 Aug;9(4):419-26
19574101
Eur J Cancer Prev. 2006 Apr;15(2):158-64
16523013
Nat Rev Cancer. 2007 Apr;7(4):256-69
17384581
N Engl J Med. 1993 May 6;328(18):1313-6
8385741
J Biol Chem. 2008 Sep 26;283(39):26428-35
18660501
Int J Epidemiol. 1993 Dec;22(6):976-82
8144310
Cancer Epidemiol Biomarkers Prev. 2000 Nov;9(11):1155-62
11097222
Cancer Epidemiol Biomarkers Prev. 1993 Jul-Aug;2(4):369-74
8348060
Am J Pathol. 2001 Sep;159(3):885-92
11549581
J Cell Biochem. 1995 Feb;57(2):256-61
7759562
Am J Physiol Gastrointest Liver Physiol. 2004 Apr;286(4):G515-20
15010360
Endocrinology. 1992 Mar;130(3):1131-44
1537280
Prostate. 2008 May 15;68(7):766-72
18302221
N Engl J Med. 1996 Mar 21;334(12):800-1
8592564
Biochem J. 2006 Feb 15;394(Pt 1):317-24
16262603
J Biol Chem. 1994 Feb 4;269(5):3155-8
8106349
Recent Results Cancer Res. 2003;163:58-71; discussion 264-6
12903843
J Urol. 2004 Feb;171(2 Pt 1):652-5
14713779
J Natl Cancer Inst. 1993 Jun 2;85(11):912-6
8492320
J Cancer Res Clin Oncol. 1991;117(4):345-50
2066355
Nutr Cancer. 2006;56(2):172-81
17474863
Cancer Epidemiol Biomarkers Prev. 2008 Feb;17(2):292-9
18268112
Cancer Epidemiol Biomarkers Prev. 1995 Jul-Aug;4(5):447-51
7549798
Can J Physiol Pharmacol. 1987 Oct;65(10):2024-35
3322538
Biochem J. 1979 Jun 15;180(3):507-13
486129
Cancer Res. 2004 Dec 1;64(23):8521-5
15574757
Biochem Soc Trans. 2007 Apr;35(Pt 2):300-4
17371265
Clin Cancer Res. 2008 Apr 15;14(8):2303-9
18413818
Clin Cancer Res. 2005 Jan 1;11(1):390-6
15671570
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7859-64
12810952
J Natl Cancer Inst. 1986 Dec;77(6):1309-13
3099048
Int J Cancer. 2000 Jan 15;85(2):243-7
10629084
Prostate. 2000 Sep 1;44(4):313-21
10951496
Cancer Prev Res (Phila). 2009 Mar;2(3):209-12
19258540
N Engl J Med. 1992 May 7;326(19):1289; author reply 1290-1
1560808
Cancer Res. 2000 Sep 15;60(18):5125-33
11016639
Photochem Photobiol. 2008 Mar-Apr;84(2):322-9
18194346
Dig Dis Sci. 2007 Mar;52(3):628-42
17253130
Urol Oncol. 2007 Sep-Oct;25(5):398-400
17826659
Cancer Prev Res (Phila). 2008 Jun;1(1):32-8
18841250
Cancer Res. 2006 Dec 1;66(23):11125-30
17145855
Cell Mol Life Sci. 2001 Feb;58(2):244-58
11289306
Inhal Toxicol. 2006 Aug;18(9):667-77
16864557
Am J Physiol. 1991 Jan;260(1 Pt 1):G45-51
1846274
J Natl Cancer Inst. 2005 Jul 6;97(13):975-80
15998950
Trends Biochem Sci. 1996 Jan;21(1):27-30
8848835
Am J Physiol Gastrointest Liver Physiol. 2004 Aug;287(2):G315-9
15246966
Carcinogenesis. 2001 Jan;22(1):83-8
11159745
Mol Carcinog. 2006 Feb;45(2):93-105
16329147
Nat Clin Pract Urol. 2007 May;4(5):240-1
17325729
N Engl J Med. 2006 Aug 31;355(9):873-84
16943400
Cell. 1990 Jun 1;61(5):759-67
2188735
Gastroenterology. 2006 Dec;131(6):1674-82
17087947
N Engl J Med. 2000 Apr 20;342(16):1156-62
10770980
Cancer Epidemiol Biomarkers Prev. 2001 Mar;10(3):191-9
11303587
Cancer. 1990 Feb 15;65(4):958-66
2297664
N Engl J Med. 1999 Jan 14;340(2):101-7
9887161
N Engl J Med. 1984 Jul 12;311(2):80-3
6738598
N Engl J Med. 2003 Mar 6;348(10):883-90
12621132
J Exp Med. 1997 May 19;185(10):1759-68
9151701
BMC Cancer. 2002 Nov 26;2:31
12453317
Adv Exp Med Biol. 1999;470:45-53
10709673
Carcinogenesis. 1990 Dec;11(12):2127-32
2265465
N Engl J Med. 2000 Apr 20;342(16):1149-55
10770979
N Engl J Med. 1992 May 7;326(19):1290; author reply 1290-1
1560810
Mol Carcinog. 2004 Feb;39(2):91-102
14750214
Inflamm Bowel Dis. 2006 Apr;12(4):278-93
16633050
Proc Natl Acad Sci U S A. 1968 Aug;60(4):1420-7
4299947
Nature. 2002 Dec 19-26;420(6917):860-7
12490959
Photochem Photobiol. 2002 Jul;76(1):73-80
12126310
Cancer Res. 2000 Jan 1;60(1):28-34
10646846
Prostate. 1992;21(3):239-45
1437858
Oncogene. 2003 Aug 11;22(33):5093-107
12910247
Breast Cancer Res Treat. 2008 Nov;112(2):255-61
18097746
Carcinogenesis. 1999 Sep;20(9):1709-13
10469614
N Engl J Med. 1991 Dec 5;325(23):1593-6
1669840
Prostate. 2002 Mar 1;50(4):252-61
11870804
Cell. 2000 Jan 7;100(1):57-70
10647931
N Engl J Med. 2000 Jun 29;342(26):1946-52
10874062
Biochimie. 2002 Aug;84(8):815-9
12457568
J Immunol. 2002 May 1;168(9):4692-700
11971019
Anticancer Drugs. 2005 Mar;16(3):229-41
15711175
Clin Cancer Res. 1999 Jan;5(1):143-7
9918212
Mol Carcinog. 2002 May;34(1):10-8
12112318
Cancer Res. 1997 Jan 15;57(2):199-201
9000553
Cancer Prev Res (Phila). 2010 Jan;3(1):35-47
20051371
Mol Carcinog. 2006 Oct;45(10):764-73
16705737
Epidemiology. 1994 Mar;5(2):138-46
8172988
N Engl J Med. 2003 Mar 6;348(10):891-9
12621133
Carcinogenesis. 1999 Mar;20(3):425-30
10190557
Proc Am Thorac Soc. 2006 Aug;3(6):535-7
16921139
J Clin Invest. 2004 Mar;113(6):867-75
15067319
J Biol Chem. 2003 Nov 28;278(48):47762-75
14506281
Cancer Epidemiol Biomarkers Prev. 1994 Jun;3(4):325-30
8061581
Shock. 1999 Feb;11(2):115-9
10030798
J Natl Cancer Inst. 2006 Oct 18;98(20):1494-500
17047198
J Biol Chem. 2004 Sep 17;279(38):40076-83
15252047
N Engl J Med. 2006 Aug 31;355(9):885-95
16943401
Genomics. 2002 Apr;79(4):505-12
11944982
J Urol. 2006 Aug;176(2):500-4
16813878