title: Pathogenesis of prostate cancer and hormone refractory prostate cancer.
abstract: Prostate cancer is the second most common malignancy in males and the leading cause of cancer death. Prostate cancer is initially androgen dependent and relies upon the androgen receptor (AR) to mediate the effects of androgens. The AR is also the target for therapy using antiandrogens and LHRH analogues. However, all cancers eventually become androgen independent, often referred to as hormone refractory prostate cancer. The processes involved in this transformation are yet to be fully understood but research in this area has discovered numerous potential mechanisms including AR amplification, over-expression or mutation and alterations in the AR signaling pathway. This review of the recent literature examines the current knowledge and developments in the understanding of the molecular biology of prostate cancer and hormone refractory prostate cancer, summarizing the well characterized pathways involved as well as introducing new concepts that may offer future solutions to this difficult problem.
authors.affiliation: CRUK Uro-oncolgy Group, Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, CB2 2XZ, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Girling
authors.forename: H C
authors.initials: HC
authors.lastname: Whitaker
authors.forename: I G
authors.initials: IG
authors.lastname: Mills
authors.forename: D E
authors.initials: DE
authors.lastname: Neal
references.citation: Cancer. 1993 Dec 15;72(12 Suppl):3888-95
references.pmid: 8252511
references.citation: J Pathol. 2005 Mar;205(4):522-9
references.pmid: 15685688
references.citation: Br J Cancer. 2006 Jun 19;94(12):1906-12
references.pmid: 16721361
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7379-84
references.pmid: 9636157
references.citation: Br J Cancer. 2004 Jan 26;90(2):449-54
references.pmid: 14735192
references.citation: Prostate. 2004 Nov 1;61(3):276-90
references.pmid: 15368471
references.citation: Endocr Rev. 1999 Jun;20(3):321-44
references.pmid: 10368774
references.citation: Clin Cancer Res. 2004 Feb 1;10(3):1032-40
references.pmid: 14871982
references.citation: Cancer Res. 2001 May 1;61(9):3550-5
references.pmid: 11325816
references.citation: Mol Endocrinol. 1999 Jan;13(1):117-28
references.pmid: 9892017
references.citation: FEBS Lett. 2002 Jul 17;523(1-3):43-7
references.pmid: 12123801
references.citation: Traffic. 2005 Dec;6(12):1103-13
references.pmid: 16262722
references.citation: Cancer Res. 2004 Jan 15;64(2):765-71
references.pmid: 14744796
references.citation: Urology. 1995 Mar;45(3):542-9
references.pmid: 7879350
references.citation: Lab Invest. 2001 Dec;81(12):1647-51
references.pmid: 11742035
references.citation: Cell. 1997 Aug 8;90(3):569-80
references.pmid: 9267036
references.citation: Nat Med. 2000 Jun;6(6):703-6
references.pmid: 10835690
references.citation: Anticancer Res. 2005 Nov-Dec;25(6C):4595-8
references.pmid: 16334148
references.citation: Prostate Suppl. 1989;2:33-50
references.pmid: 2482772
references.citation: Cancer Res. 1997 Jan 15;57(2):314-9
references.pmid: 9000575
references.citation: Cancer Res. 2005 Sep 1;65(17):7959-67
references.pmid: 16140968
references.citation: Biochem J. 2004 Oct 15;383(Pt 2):267-76
references.pmid: 15239671
references.citation: Clin Cancer Res. 2004 Nov 1;10(21):7121-6
references.pmid: 15534082
references.citation: J Mol Endocrinol. 2000 Jun;24(3):339-51
references.pmid: 10828827
references.citation: J Urol. 2001 Oct;166(4):1514-9
references.pmid: 11547123
references.citation: Int J Cancer. 2006 Mar 1;118(5):1108-19
references.pmid: 16161052
references.citation: Cancer. 2006 Jun 15;106(12):2743-52
references.pmid: 16703599
references.citation: Nat Genet. 1995 Apr;9(4):401-6
references.pmid: 7795646
references.citation: Urology. 2001 Aug;58(2):289-94
references.pmid: 11489729
references.citation: Clin Cancer Res. 2002 Apr;8(4):1168-71
references.pmid: 11948129
references.citation: J Cell Biol. 2005 Jul 18;170(2):191-200
references.pmid: 16027218
references.citation: Cancer Cell. 2003 May;3(5):471-82
references.pmid: 12781365
references.citation: Biochem Pharmacol. 2004 Sep 15;68(6):1199-208
references.pmid: 15313417
references.citation: Mol Cell Biol. 2001 Jan;21(1):39-50
references.pmid: 11113179
references.citation: J Steroid Biochem Mol Biol. 2001 Jan-Mar;76(1-5):135-42
references.pmid: 11384871
references.citation: J Natl Cancer Inst. 2001 Nov 21;93(22):1687-97
references.pmid: 11717329
references.citation: J Urol. 2000 Dec;164(6):1992-5
references.pmid: 11061898
references.citation: Nat Med. 2004 Jan;10(1):33-9
references.pmid: 14702632
references.citation: Genes Dev. 2006 Jun 15;20(12):1569-74
references.pmid: 16778075
references.citation: Prostate. 2006 Jun 15;66(9):895-902
references.pmid: 16496415
references.citation: J Natl Cancer Inst. 2000 Dec 6;92(23):1918-25
references.pmid: 11106683
references.citation: Urol Clin North Am. 2006 May;33(2):201-10, vii
references.pmid: 16631458
references.citation: Mol Endocrinol. 1997 Apr;11(4):450-9
references.pmid: 9092797
references.citation: J Biol Chem. 2003 Dec 19;278(51):50902-7
references.pmid: 14555644
references.citation: Hum Mol Genet. 2001 Aug 15;10(17):1807-17
references.pmid: 11532990
references.citation: Cancer Cells. 1990 Nov;2(11):345-54
references.pmid: 2282250
references.citation: Cancer Res. 1998 Oct 15;58(20):4640-5
references.pmid: 9788616
references.citation: Am J Pathol. 2003 Jan;162(1):233-41
references.pmid: 12507906
references.citation: J Biol Chem. 2004 Feb 20;279(8):7119-30
references.pmid: 14662770
references.citation: Prostate. 2003 May 1;55(2):128-39
references.pmid: 12661038
references.citation: Cancer Res. 2003 Nov 15;63(22):7638-40
references.pmid: 14633682
references.citation: J Clin Invest. 2002 Aug;110(3):351-60
references.pmid: 12163454
references.citation: Cancer Res. 1994 Jun 1;54(11):2861-4
references.pmid: 8187068
references.citation: Exp Cell Res. 1999 Dec 15;253(2):349-56
references.pmid: 10585257
references.citation: Cancer Res. 1999 Jan 15;59(2):279-84
references.pmid: 9927031
references.citation: Exp Cell Res. 2006 Oct 1;312(16):3165-83
references.pmid: 16860317
references.citation: Cancer Res. 1999 Feb 15;59(4):803-6
references.pmid: 10029066
references.citation: Mol Cell Biol. 2002 Jun;22(11):3621-32
references.pmid: 11997499
references.citation: Cancer Metastasis Rev. 2001;20(3-4):207-23
references.pmid: 12085963
references.citation: Cancer Res. 1994 Oct 15;54(20):5474-8
references.pmid: 7522959
references.citation: Cancer Res. 2001 Jun 1;61(11):4315-9
references.pmid: 11389051
references.citation: Mol Endocrinol. 2006 May;20(5):1048-60
references.pmid: 16373395
references.citation: Mol Endocrinol. 1998 Aug;12(8):1172-83
references.pmid: 9717843
references.citation: J Pathol. 2000 Jul;191(3):239-44
references.pmid: 10878544
references.citation: Surg Oncol. 2005 Aug;14(2):91-104
references.pmid: 15993579
references.citation: Cancer Res. 1998 Dec 15;58(24):5718-24
references.pmid: 9865729
references.citation: Int J Cancer. 1991 May 10;48(2):189-93
references.pmid: 1708363
references.citation: Cancer Res. 1999 May 1;59(9):2203-9
references.pmid: 10232609
references.citation: Trends Mol Med. 2004 Apr;10(4):194-9
references.pmid: 15059611
references.citation: J Urol. 2003 Nov;170(5):1817-21
references.pmid: 14532783
references.citation: Hum Mutat. 1999;14(2):103-14
references.pmid: 10425033
references.citation: J Biol Chem. 2006 Sep 22;281(38):27882-93
references.pmid: 16870607
references.citation: Endocr Relat Cancer. 2004 Dec;11(4):709-24
references.pmid: 15613447
references.citation: Clin Cancer Res. 2003 Nov 1;9(14):5271-81
references.pmid: 14614009
references.citation: Nature. 1997 Sep 11;389(6647):194-8
references.pmid: 9296499
references.citation: FEBS Lett. 2002 Aug 28;526(1-3):142-6
references.pmid: 12208521
references.citation: Eur J Cancer. 2006 Jun;42(9):1213-8
references.pmid: 16632344
references.citation: Trends Endocrinol Metab. 2001 Jul;12(5):186-8
references.pmid: 11592245
references.citation: J Biol Chem. 2003 Feb 14;278(7):5052-61
references.pmid: 12441355
references.citation: Br J Cancer. 2001 Dec 14;85(12):1928-36
references.pmid: 11747336
references.citation: Cancer Res. 1999 Jun 1;59(11):2511-5
references.pmid: 10363963
references.citation: Clin Cancer Res. 2005 Jul 1;11(13):4653-7
references.pmid: 16000557