title: Beyond CA125: the coming of age of ovarian cancer biomarkers. Are we there yet?
abstract: Ovarian cancer (OC) is the fourth leading cause of cancer deaths among women in the United States, despite its relatively low incidence of 50 per 100,000. Even though advances in therapy have been made, the OC fatality-to-case ratio remains exceedingly high, due to the lack of accurate tools to diagnose early-stage disease when cure is still possible. The most studied marker for OC, CA125, is only expressed by 50-60% of patients with early stage disease. Large efforts have been deployed to identify novel serum markers, yet no single marker has emerged as a serious competitor for CA125. Various groups are investing in combination approaches to increase the diagnostic value of existing markers, but many markers may still lie in under-explored areas of ovarian cancer biology, such as tumor vasculature environment and post-translational modifications (glycomics).
authors.affiliation: University of Pennsylvania School of Medicine, 421 Curie Boulevard, BRBII/III, PA, USA.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Sasaroli
authors.forename: George
authors.initials: G
authors.lastname: Coukos
authors.forename: Nathalie
authors.initials: N
authors.lastname: Scholler
references.citation: N Engl J Med. 2005 Sep 22;353(12):1224-35
references.pmid: 16177248
references.citation: Cancer Res. 2003 Jul 1;63(13):3695-700
references.pmid: 12839961
references.citation: Endocr Rev. 2001 Apr;22(2):255-88
references.pmid: 11294827
references.citation: Mol Cancer. 2006 Oct 26;5(1):50
references.pmid: 17067392
references.citation: Proc Natl Acad Sci U S A. 2005 May 24;102(21):7677-82
references.pmid: 15890779
references.citation: Am J Obstet Gynecol. 2004 Sep;191(3):718-32
references.pmid: 15467531
references.citation: Glycobiology. 2006 Feb;16(2):132-45
references.pmid: 16177264
references.citation: Int J Cancer. 2002 Apr 10;98(5):737-40
references.pmid: 11920644
references.citation: Am J Pathol. 2004 Aug;165(2):601-8
references.pmid: 15277233
references.citation: Gynecol Oncol. 1994 Mar;52(3):301-5
references.pmid: 7512519
references.citation: Clin Cancer Res. 2008 Nov 15;14(22):7574; author reply 7577-9
references.pmid: 18948386
references.citation: Biomark Med. 2007 Dec;1(4):513-23
references.pmid: 20477371
references.citation: Clin Chem. 2008 Oct;54(10):1600-7
references.pmid: 18687738
references.citation: Int J Gynecol Cancer. 2006 Jan-Feb;16 Suppl 1:54-9
references.pmid: 16515568
references.citation: J Natl Cancer Inst. 1999 Sep 1;91(17):1459-67
references.pmid: 10469746
references.citation: Science. 2000 Aug 18;289(5482):1197-202
references.pmid: 10947988
references.citation: J Proteome Res. 2007 Jul;6(7):2509-17
references.pmid: 17547437
references.citation: Cancer Lett. 2007 Apr 28;249(1):14-7
references.pmid: 17320281
references.citation: Int J Cancer. 1996 Aug 22;69(4):283-9
references.pmid: 8797869
references.citation: Lancet Oncol. 2009 Apr;10(4):327-40
references.pmid: 19282241
references.citation: Nature. 2001 May 17;411(6835):375-9
references.pmid: 11357145
references.citation: J Clin Oncol. 2005 Aug 20;23(24):5588-96
references.pmid: 16110018
references.citation: Hematol Oncol Clin North Am. 2003 Aug;17(4):989-1005, ix
references.pmid: 12959188
references.citation: Biotechniques. 2001 Mar;30(3):670-5
references.pmid: 11252802
references.citation: Mol Immunol. 1997 Jan;34(1):9-20
references.pmid: 9182872
references.citation: J Clin Endocrinol Metab. 2002 Feb;87(2):816-24
references.pmid: 11836327
references.citation: Eur J Obstet Gynecol Reprod Biol. 1997 Dec;75(2):205-6
references.pmid: 9447374
references.citation: J Clin Invest. 1981 Nov;68(5):1331-7
references.pmid: 7028788
references.citation: Clin Cancer Res. 2007 Dec 1;13(23):6984-92
references.pmid: 18056174
references.citation: Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2117-24
references.pmid: 16609024
references.citation: Nature. 2007 Dec 20;450(7173):1235-9
references.pmid: 18097410
references.citation: Cancer Res. 2007 Feb 15;67(4):1757-68
references.pmid: 17308118
references.citation: J Proteome Res. 2008 Jan;7(1):319-27
references.pmid: 18047267
references.citation: Anticancer Res. 1999 Mar-Apr;19(2B):1401-5
references.pmid: 10365113
references.citation: Gynecol Oncol. 2008 Sep;110(3):374-82
references.pmid: 18584856
references.citation: Br J Cancer. 2002 Jul 29;87(3):339-43
references.pmid: 12177805
references.citation: Am J Obstet Gynecol. 1991 Nov;165(5 Pt 1):1356-62
references.pmid: 1957862
references.citation: Cancer Res. 1984 Mar;44(3):1048-53
references.pmid: 6198078
references.citation: Am J Surg Pathol. 2006 Feb;30(2):230-6
references.pmid: 16434898
references.citation: Expert Opin Ther Targets. 2005 Dec;9(6):1203-16
references.pmid: 16300471
references.citation: Clin Cancer Res. 1997 Apr;3(4):605-11
references.pmid: 9815727
references.citation: Dis Markers. 2007;23(5-6):419-31
references.pmid: 18057525
references.citation: Mol Cell Proteomics. 2004 Apr;3(4):355-66
references.pmid: 14764655
references.citation: Cancer Res. 2003 May 1;63(9):2223-7
references.pmid: 12727843
references.citation: J Clin Oncol. 2008 Nov 10;26(32):5284-93
references.pmid: 18854563
references.citation: J Biol Chem. 2004 Mar 5;279(10):9190-8
references.pmid: 14676194
references.citation: Anticancer Res. 2000 Nov-Dec;20(6D):5109-12
references.pmid: 11326678
references.citation: J Exp Med. 1998 Apr 20;187(8):1163-7
references.pmid: 9547328
references.citation: Mol Cell Proteomics. 2009 May;8(5):995-1005
references.pmid: 19196707
references.citation: Gynecol Oncol. 2008 Feb;108(2):402-8
references.pmid: 18061248
references.citation: Int J Cancer. 1997 May 16;71(4):638-44
references.pmid: 9178820
references.citation: Clin Med Res. 2007 Mar;5(1):35-44
references.pmid: 17456833
references.citation: Nat Immunol. 2008 Nov;9(11):1225-35
references.pmid: 18820683
references.citation: Gynecol Oncol. 2005 May;97(2):476-82
references.pmid: 15863147
references.citation: N Engl J Med. 1983 Oct 13;309(15):883-7
references.pmid: 6310399
references.citation: J Immunother. 2000 Jul-Aug;23(4):473-9
references.pmid: 10916757
references.citation: Nat Rev Cancer. 2004 Nov;4(11):876-90
references.pmid: 15516960
references.citation: J Clin Oncol. 2005 Nov 1;23(31):7919-26
references.pmid: 16258091
references.citation: Gynecol Oncol. 2005 Nov;99(2):267-77
references.pmid: 16061277
references.citation: Gynecol Oncol. 2004 Oct;95(1):9-15
references.pmid: 15385104
references.citation: Nature. 2008 Apr 3;452(7187):571-9
references.pmid: 18385731
references.citation: J Immunol. 2002 Jul 15;169(2):1102-9
references.pmid: 12097419
references.citation: Int J Cancer. 2009 Feb 15;124(4):919-23
references.pmid: 19035463
references.citation: Gene. 2007 Sep 15;399(2):137-43
references.pmid: 17560052
references.citation: Clin Chem. 2008 Mar;54(3):582-9
references.pmid: 18171715
references.citation: Crit Rev Biochem Mol Biol. 1997;32(1):1-100
references.pmid: 9063619
references.citation: Fertil Steril. 2001 Jun;75(6):1218-21
references.pmid: 11384653
references.citation: Arch Biochem Biophys. 2004 Jun 15;426(2):122-31
references.pmid: 15158662
references.citation: Hum Pathol. 2005 Jan;36(1):44-50
references.pmid: 15712181
references.citation: Am J Obstet Gynecol. 1991 Apr;164(4):1038-42; discussion 1042-3
references.pmid: 2014824
references.citation: Lancet Oncol. 2008 Nov;9(11):1076-85
references.pmid: 19012856
references.citation: PLoS One. 2007 Dec 05;2(12):e1281
references.pmid: 18060075
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17494-9
references.pmid: 17954908
references.citation: Cancer Res. 2004 Nov 1;64(21):7857-66
references.pmid: 15520192
references.citation: Arthritis Rheum. 2006 Nov;54(11):3433-40
references.pmid: 17075835
references.citation: N Engl J Med. 1993 Nov 18;329(21):1539-42
references.pmid: 8413476
references.citation: Am J Obstet Gynecol. 2008 Sep;199(3):215-23
references.pmid: 18468571
references.citation: Gynecol Oncol. 2006 Aug;102(2):244-51
references.pmid: 16434085
references.citation: Clin Cancer Res. 2006 Jan 15;12(2):447-53
references.pmid: 16428485
references.citation: Clin Cancer Res. 2008 Feb 15;14(4):1065-72
references.pmid: 18258665
references.citation: J Biol Chem. 2001 Jul 20;276(29):27371-5
references.pmid: 11369781
references.citation: Cancer Res. 2006 Jan 15;66(2):1181-90
references.pmid: 16424057
references.citation: Gynecol Oncol. 2006 Dec;103(3):1077-82
references.pmid: 16904167
references.citation: Cancer Lett. 2007 Oct 8;255(2):263-74
references.pmid: 17560019
references.citation: Mol Cell Endocrinol. 2001 Jun 30;180(1-2):73-7
references.pmid: 11451574
references.citation: JAMA. 2002 Apr 3;287(13):1671-9
references.pmid: 11926891
references.citation: Cancer Lett. 2007 Mar 8;247(1):130-6
references.pmid: 16677756
references.citation: Cancer. 1994 Apr 1;73(7):1855-8
references.pmid: 8137210
references.citation: Cell. 2007 Aug 10;130(3):395-8
references.pmid: 17693247
references.citation: Gene. 1999 Oct 1;238(2):375-85
references.pmid: 10570965
references.citation: Int J Gynecol Pathol. 2008 Jan;27(1):1-9
references.pmid: 18156967
references.citation: Clin Cancer Res. 2002 Oct;8(10):3193-7
references.pmid: 12374688
references.citation: J Transl Med. 2008 Jul 24;6:41
references.pmid: 18652693
references.citation: Cancer Res. 2005 Dec 1;65(23):10794-800
references.pmid: 16322225
references.citation: CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
references.pmid: 18287387
references.citation: J Immunol Methods. 2006 Dec 20;317(1-2):132-43
references.pmid: 17113097
references.citation: J Clin Oncol. 2002 Mar 1;20(5):1260-8
references.pmid: 11870168
references.citation: Proteomics. 2007 Nov;7(22):4045-52
references.pmid: 17952875
references.citation: Eur J Cancer. 2005 Mar;41(4):549-54
references.pmid: 15737559
references.citation: Science. 2006 Aug 4;313(5787):670-3
references.pmid: 16888140
references.citation: Gynecol Oncol. 2006 Jan;100(1):20-6
references.pmid: 16188302
references.citation: J Virol Methods. 1998 Jul;73(1):99-107
references.pmid: 9705181
references.citation: Clin Cancer Res. 2006 Jan 15;12(2):323-7
references.pmid: 16428467
references.citation: Gynecol Oncol. 2008 May;109(2):168-73
references.pmid: 18342932
references.citation: Lancet. 2002 Jul 13;360(9327):170; author reply 170-1
references.pmid: 12126845
references.citation: Lancet. 2003 Nov 15;362(9396):1612-6
references.pmid: 14630441
references.citation: JAMA. 1998 Aug 26;280(8):719-23
references.pmid: 9728644
references.citation: Br J Cancer. 2006 Mar 27;94(6):814-9
references.pmid: 16495917
references.citation: Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11531-6
references.pmid: 10500211
references.citation: J Natl Cancer Inst. 1996 Nov 20;88(22):1652-8
references.pmid: 8931609
references.citation: Glycobiology. 2007 Dec;17(12):1344-56
references.pmid: 17884841
references.citation: Int J Gynecol Cancer. 2002 Jan-Feb;12(1):86-91
references.pmid: 11860541
references.citation: Proteomics. 2008 Aug;8(16):3284-93
references.pmid: 18646009
references.citation: J Clin Oncol. 2007 Sep 1;25(25):3985-90
references.pmid: 17761984
references.citation: Int J Gynecol Cancer. 2005 Nov-Dec;15 Suppl 3:274-81
references.pmid: 16343244
references.citation: Cancer Sci. 2008 Feb;99(2):432-40
references.pmid: 18271942
references.citation: Science. 1992 Dec 11;258(5089):1798-801
references.pmid: 1281554
references.citation: Gynecol Oncol. 2009 Jan;112(1):185-91
references.pmid: 18954898
references.citation: Clin Cancer Res. 2008 Nov 15;14(22):7574; author reply 7577-9
references.pmid: 18948385
references.citation: J Clin Oncol. 2007 Mar 1;25(7):852-61
references.pmid: 17327606
references.citation: J Pathol. 2007 Jan;211(1):26-35
references.pmid: 17117391
references.citation: Mol Cell Proteomics. 2002 Mar;1(3):197-203
references.pmid: 12096119
references.citation: Cancer Lett. 2007 Apr 28;249(1):61-79
references.pmid: 17275179
references.citation: Clin Cancer Res. 2007 Mar 1;13(5):1571-5
references.pmid: 17332303
references.citation: J Clin Invest. 1992 Mar;89(3):1021-31
references.pmid: 1347295
references.citation: Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):136-40
references.pmid: 8552591
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):981-7
references.pmid: 15824174
references.citation: Cancer. 2002 Aug 1;95(3):506-12
references.pmid: 12209742
references.citation: J Proteome Res. 2007 Sep;6(9):3558-65
references.pmid: 17696519
references.citation: Ann Oncol. 2007 Feb;18(2):269-74
references.pmid: 17065588
references.citation: Biomaterials. 1990 Nov;11(9):615-8
references.pmid: 1708683
references.citation: J Clin Oncol. 2003 May 15;21(10 Suppl):200s-205s
references.pmid: 12743135
references.citation: Gynecol Oncol. 1992 Feb;44(2):147-54
references.pmid: 1312052
references.citation: Cancer. 2000 Nov 15;89(10):2068-75
references.pmid: 11066047
references.citation: Clin Cancer Res. 2004 May 15;10(10):3474-8
references.pmid: 15161704
references.citation: Cancer. 1996 Nov 15;78(10):2146-52
references.pmid: 8918407
references.citation: Int J Cancer. 1994 Apr 1;57(1):90-7
references.pmid: 8150545
references.citation: Br J Cancer. 2007 Jan 29;96(2):362-72
references.pmid: 17242704
references.citation: Int J Cancer. 2003 Nov 10;107(3):359-64
references.pmid: 14506734