title: The current status of tailor-made medicine with molecular biomarkers for patients with clear cell renal cell carcinoma.
abstract: Appropriate use of multiple reliable molecular biomarkers in the right context will play a role in tailormade medicine of clear cell renal cell carcinoma (RCC) patients in the future. A total of 11,056 patients from 53 studies were included in this review. The article numbers of the each evidence levels, using the grading system defined by the Oxford Centre for Evidence-based Medicine, in 1b, 2a, 2b, and 3b were 5 (9%), 18 (34%), 29 (55%), and 1 (2%), respectively. The main goal of using biomarkers is to refine predictions of tumor progression, pharmacotherapy responsiveness, and cancer-specific and/or overall survival. Currently, carbonic anhydrase (CA9) and vascular endothelial growth factor (VEGF) in peripheral blood and p53 in tumor tissues are measured to predict metastasis, while VEGF-related proteins in peripheral blood are used to assess pharmacotherapy responsiveness with sunitinib. Furthermore, interleukin 8, osteopontin, hepatocyte growth factor, and tissue inhibitors of metalloproteinases-1 in peripheral blood enable assessment of responsiveness to pazopanib treatment. Other reliable molecular biomarkers include von Hippel–Lindau gene alteration, hypoxia-inducible factor-1a, CA9, and survivin in tumor tissues and VEGF in peripheral blood for predicting cancer-specific survival. In the future, studies should undergo external validation for developing tailored management of clear cell RCC with molecular biomarkers, since individual institutional studies lack the generalization and consistency required to maintain accuracy among different patient series.
authors: Sunao
authors: S
authors: Shoji
authors: Mayura
authors: M
authors: Nakano
authors: Haruhiro
authors: H
authors: Sato
authors: Xian Yang
authors: XY
authors: Tang
authors: Yoshiyuki Robert
authors: YR
authors: Osamura
authors: Toshiro
authors: T
authors: Terachi
authors: Toyoaki
authors: T
authors: Uchida
authors: Koichi
authors: K
authors: Takeya
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism; D057285:Precision Medicine / Q000639:trends*
chemical_list: D014408:Biomarkers, Tumor
references: BJU Int. 2012 Oct;110(7):956-60
references: 22300498
references: Int J Cancer. 2000 Apr 15;86(2):162-8
references: 10738241
references: Curr Opin Cell Biol. 2004 Oct;16(5):590-6
references: 15363811
references: Proc Natl Acad Sci U S A. 2005 May 24;102(21):7677-82
references: 15890779
references: J Exp Med. 1996 Sep 1;184(3):1101-9
references: 9064327
references: J Urol. 2008 Jan;179(1):61-6
references: 17997430
references: Urology. 2006 Sep;68(3):518-22
references: 16979727
references: Nature. 2010 Oct 28;467(7319):1109-13
references: 20981101
references: Cancer Res. 1987 Jun 1;47(11):2883-91
references: 3552208
references: Cancer Res. 1999 Dec 15;59(24):6097-102
references: 10626797
references: Biochim Biophys Acta. 1999 Oct 8;1455(2-3):301-13
references: 10571020
references: J Urol. 2000 Jan;163(1):343-7
references: 10604387
references: BJU Int. 1999 Sep;84(4):405-11
references: 10468753
references: Development. 1995 Aug;121(8):2407-18
references: 7671806
references: Clin Cancer Res. 2007 Dec 15;13(24):7388-93
references: 18094421
references: Mol Cancer. 2009 Nov 14;8:102
references: 19912656
references: BJU Int. 2011 Sep;108(5):665-72
references: 21265994
references: Cancer Res. 1991 Dec 1;51(23 Pt 1):6328-37
references: 1933895
references: J Natl Cancer Inst. 2008 Oct 15;100(20):1454-63
references: 18840822
references: N Engl J Med. 1991 Jan 3;324(1):1-8
references: 1701519
references: Cell. 1995 Nov 3;83(3):493-501
references: 8521479
references: Urology. 2004 Apr;63(4):651-5
references: 15072872
references: Anticancer Res. 2012 Dec;32(12):5447-51
references: 23225450
references: Cancer Res. 1992 Feb 1;52(3):701-8
references: 1732058
references: Cancer Metastasis Rev. 2012 Sep;31 Suppl 1:S29-32
references: 22723081
references: Clin Cancer Res. 2005 May 15;11(10):3714-21
references: 15897568
references: PLoS Med. 2009 Jul 21;6(7):e1000100
references: 19621070
references: BJU Int. 2011 Jun;107(11):1722-32
references: 21251188
references: J Clin Invest. 2008 Jan;118(1):217-28
references: 18079963
references: Lancet Oncol. 2007 Feb;8(2):128-36
references: 17267327
references: Prostate. 2002 Feb 15;50(3):189-201
references: 11813211
references: J Clin Oncol. 2009 Jun 1;27(16):2645-52
references: 19364969
references: Cancer. 2005 Oct 1;104(7):1362-71
references: 16116599
references: Annu Rev Physiol. 1995;57:607-34
references: 7778880
references: BJU Int. 2007 Sep;100(3):556-60
references: 17608827
references: Am J Surg Pathol. 2011 Oct;35(10):1549-56
references: 21881486
references: Clin Chem. 2008 Aug;54(8):e1-e10
references: 18606634
references: Eur Urol. 1995;28(3):251-4
references: 8536781
references: Oncologist. 2011;16(12):1729-40
references: 22135123
references: Urol Int. 2008;80(2):113-23
references: 18362478
references: Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):680s-684s
references: 17255293
references: Science. 2008 Nov 28;322(5906):1377-80
references: 19039135
references: Clin Cancer Res. 2004 Aug 15;10(16):5464-71
references: 15328185
references: J Clin Oncol. 2008 Aug 1;26(22):3743-8
references: 18669461
references: Cancer. 2008 Apr 1;112(7):1471-9
references: 18260086
references: Clin Cancer Res. 2003 Feb;9(2):802-11
references: 12576453
references: Oncol Lett. 2010 Sep;1(5):783-788
references: 22966379
references: Mol Cell Biol. 1999 Feb;19(2):1262-70
references: 9891060
references: Eur Urol. 2010 May;57(5):859-66
references: 19747761
references: Cancer Detect Prev. 2002;26(3):222-8
references: 12269770
references: J Urol. 2008 Aug;180(2):510-3; discussion 513-4
references: 18550116
references: Ann Hum Genet. 1987 Oct;51(4):289-94
references: 3447512
references: Clin Exp Metastasis. 2013 Jun;30(5):607-14
references: 23277422
references: BJU Int. 2009 Oct;104(7):942-6
references: 19388989
references: Br J Cancer. 2012 Feb 28;106(5):904-8
references: 22294183
references: Annu Rev Pharmacol Toxicol. 1990;30:1-45
references: 2111654
references: Nat Rev Cancer. 2008 Mar;8(3):212-26
references: 18292776
references: J Immunol. 1984 Oct;133(4):1710-5
references: 6206131
references: Exp Cell Res. 2003 Nov 1;290(2):332-45
references: 14567991
references: Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4240-5
references: 10200246
references: N Engl J Med. 2012 Mar 8;366(10):883-892
references: 22397650
references: Int J Cancer. 2008 Jul 15;123(2):395-400
references: 18464292
references: Cancer. 2007 Jun 1;109(11):2257-67
references: 17440983
references: N Engl J Med. 2007 Jan 11;356(2):185-7
references: 17215538
references: Eur Urol. 2006 Apr;49(4):633-43
references: 16481093
references: J Clin Oncol. 1999 Aug;17(8):2530-40
references: 10561319
references: J Clin Oncol. 2007 Apr 10;25(11):1316-22
references: 17416852
references: Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1387-92
references: 11171960
references: Genes Dev. 2004 Aug 15;18(16):1926-45
references: 15314020
references: Int J Cancer. 2002 Jun 20;99(6):821-8
references: 12115483
references: Mech Dev. 1999 Oct;88(1):95-9
references: 10525192
references: Clin Cancer Res. 2006 Dec 1;12(23):6998-7003
references: 17145820
references: Eur Urol. 2007 Sep;52(3):791-7
references: 17207914
references: Oncol Lett. 2010 Nov;1(6):1073-1078
references: 22870115
references: Nat Rev Cancer. 2006 Apr;6(4):259-69
references: 16557279
references: Nat Rev Genet. 2009 Aug;10(8):578-85
references: 19609263
references: J Urol. 2008 Sep;180(3):860-5; discussion 865-6
references: 18635227
references: Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):894-900
references: 19240241
references: Int J Mol Med. 2004 Feb;13(2):229-33
references: 14719128
references: Clin Cancer Res. 2000 Dec;6(12):4866-73
references: 11156246
references: Cancer Lett. 2008 Aug 28;267(2):226-44
references: 18579287
references: J Biol Chem. 2005 May 6;280(18):18517-24
references: 15753088
references: J Urol. 2011 Feb;185(2):433-8
references: 21167521
references: Urology. 2009 Feb;73(2):394-9
references: 18849062
references: Virchows Arch. 2000 Feb;436(2):119-26
references: 10755601
references: J Pathol. 2002 Feb;196(2):186-93
references: 11793370
references: Anticancer Res. 2010 Jul;30(7):3023-30
references: 20683050
references: Lancet Oncol. 2011 Nov;12(12):1143-50
references: 22015057
references: Jpn J Clin Oncol. 2011 Mar;41(3):411-6
references: 21062756
references: APMIS. 2008 Jul-Aug;116(7-8):586-601
references: 18834404
references: Can J Urol. 2009 Aug;16(4):4726-32
references: 19671223
references: Eur J Biochem. 1999 Oct;265(2):501-23
references: 10504381
references: Clin Cancer Res. 2002 Apr;8(4):1157-67
references: 11948128
references: Nature. 2003 Sep 18;425(6955):307-11
references: 13679920
references: Lancet Oncol. 2012 Aug;13(8):827-37
references: 22759480
references: Cancer Res. 2000 Mar 1;60(5):1306-11
references: 10728691
references: Eur J Cancer. 2010 Dec;46(18):3375-82
references: 20709525
references: BJU Int. 2011 Nov;108(10):1556-63
references: 21952069
references: Ann Oncol. 2010 Aug;21(8):1599-1606
references: 20089566
references: Cell Oncol. 2009;31(5):371-82
references: 19759417
references: Cancer Res. 2002 Jan 15;62(2):403-8
references: 11809688
references: Physiol Rev. 2002 Apr;82(2):373-428
references: 11917093
references: Am J Pathol. 2001 Apr;158(4):1279-88
references: 11290546
references: Urology. 2007 Jun;69(6):1049-53
references: 17572184
references: J Urol. 2009 Aug;182(2):728-34
references: 19539328
references: Int Urol Nephrol. 2010 Jun;42(2):295-8
references: 19572207
references: Science. 2003 May 9;300(5621):987-90
references: 12738867
references: Anticancer Res. 2011 Feb;31(2):597-605
references: 21378344
references: Curr Treat Options Oncol. 2012 Jun;13(2):212-29
references: 22410708
references: Clin Exp Metastasis. 2012 Oct;29(7):657-62
references: 22692562
references: Biochim Biophys Acta. 1995 Oct 26;1259(1):109-19
references: 7492609
references: J Cell Biol. 1989 Jun;108(6):2435-47
references: 2661563
references: Cancer Res. 2003 Dec 15;63(24):8614-22
references: 14695172
references: Clin Cancer Res. 2004 Aug 1;10(15):5094-100
references: 15297412
references: Oncogene. 1999 Jan 28;18(4):869-76
references: 10023662
references: Br J Cancer. 2000 Jun;82(11):1808-13
references: 10839295
references: N Engl J Med. 2007 Jan 11;356(2):115-24
references: 17215529
references: Cancer Treat Rev. 2003 May;29 Suppl 1:3-9
references: 12738238
references: Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491-5
references: 1323840
references: J Clin Oncol. 2005 Apr 20;23(12):2763-71
references: 15837991
references: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10691-6
references: 15249675
references: J Natl Cancer Inst. 1997 Sep 3;89(17):1260-70
references: 9293916
references: Clin Cancer Res. 2008 Feb 1;14(3):782-7
references: 18245539
references: Eur Urol. 2007 Dec;52(6):1601-9
references: 17919807
references: J Immunol. 2006 Feb 1;176(3):1456-64
references: 16424173
references: Nat Rev Mol Cell Biol. 2010 Apr;11(4):252-63
references: 20216554
references: Nat Med. 2002 Aug;8(8):793-800
references: 12091876
references: BJU Int. 2010 Sep;106(6):772-8
references: 20230385
references: Eur Urol. 2006 Jul;50(1):92-7; discussion 97
references: 16426736
references: J Pathol. 2011 Jan;223(1):46-53
references: 20922711
references: J Exp Clin Cancer Res. 2009 Mar 20;28:40
references: 19302703
references: Nature. 2011 Apr 7;472(7341):90-4
references: 21399628
references: Genes Dev. 1990 Jan;4(1):1-8
references: 2137806
references: Cancer. 2006 Jul 1;107(1):37-45
references: 16736510
references: Cancer Cell. 2003 Mar;3(3):203-5
references: 12676578
references: Clin Cancer Res. 2005 Jan 1;11(1):186-92
references: 15671545
references: Ann Oncol. 2005 May;16 Suppl 4:iv74-79
references: 15923435
references: Cell. 2003 Nov 26;115(5):577-90
references: 14651849
references: J Biol Chem. 1999 Jul 30;274(31):21491-4
references: 10419448
references: Clin Cancer Res. 2005 Jul 15;11(14):5128-39
references: 16033827
references: EMBO J. 1988 Dec 1;7(12):3679-84
references: 3061804
references: JAMA. 2006 Jun 7;295(21):2516-24
references: 16757724
references: J Transl Med. 2007 Jul 02;5:32
references: 17605814
references: Br J Cancer. 2005 Jun 20;92(12):2171-80
references: 15928670
references: Urology. 2006 May;67(5):942-5
references: 16698354
references: Nat Rev Cancer. 2002 Mar;2(3):161-74
references: 11990853
references: Cytometry. 1991;12(5):455-63
references: 1935459
references: Am J Clin Pathol. 2002 Jul;118(1):47-51
references: 12109855
references: J Natl Cancer Inst. 2006 Sep 20;98(18):1331-4
references: 16985252
references: Curr Opin Hematol. 2000 Jan;7(1):64-9
references: 10608507
references: Nature. 2001 May 31;411(6837):613-7
references: 11385580
references: Annu Rev Med. 2009;60:167-79
references: 19630570
references: Cancer. 2007 Aug 1;110(3):543-50
references: 17577222
references: Cancer. 2006 Dec 1;107(11):2604-8
references: 17075871
references: Cancer. 2005 Mar 1;103(5):931-42
references: 15685621
references: Anticancer Res. 2006 Sep-Oct;26(5B):3825-33
references: 17094408
references: Urology. 2002 Apr;59(4):532-7
references: 11927308
references: Trends Mol Med. 2006 Dec;12(12):580-7
references: 17071139
references: Clin Cancer Res. 2012 Feb 1;18(3):645-53
references: 22156560
references: Cancer Treat Rev. 2005 Nov;31(7):536-45
references: 16236454
references: Eur Urol. 2009 Feb;55(2):441-9
references: 18395325
references: Clin Cancer Res. 2008 Nov 1;14(21):6735-41
references: 18980965
references: Cytogenet Cell Genet. 2001;92(1-2):164-5
references: 11306819
references: Curr Urol Rep. 2005 Feb;6(1):7-18
references: 15610692
references: J Natl Cancer Inst. 2002 Oct 16;94(20):1569-75
references: 12381710
references: Clin Cancer Res. 2005 Feb 1;11(3):1129-35
references: 15709180
references: Cancer Res. 2006 Apr 1;66(7):3381-5
references: 16585157
references: Cancer Res. 2002 Nov 15;62(22):6706-11
references: 12438270
references: Oncol Lett. 2012 Apr 1;3(4):787-790
references: 22740994
references: Oncol Rep. 2008 Sep;20(3):525-30
references: 18695901
references: J Clin Epidemiol. 2003 Sep;56(9):826-32
references: 14505766
references: Am J Cancer Res. 2011;1(2):240-254
references: 21969126
references: J Urol. 1998 Apr;159(4):1163-7
references: 9507823
references: Clin Cancer Res. 2011 Feb 1;17(3):620-9
references: 21097692
references: Br J Cancer. 2005 Jan 31;92(2):212-6
references: 15611788
references: Eur J Immunol. 1998 Nov;28(11):3696-705
references: 9842912
references: Clin Chem. 2009 Apr;55(4):623-31
references: 19246618
references: Clin Genitourin Cancer. 2007 Sep;5(6):379-85
references: 17956710
references: Nat Rev Cancer. 2004 Aug;4(8):592-603
references: 15286739
references: Nat Rev Mol Cell Biol. 2003 Dec;4(12):915-25
references: 14685170
references: Virchows Arch A Pathol Anat Histopathol. 1993;423(5):329-34
references: 7509541
references: Ophthalmology. 1993 Sep;100(9):1389-98
references: 8371929
references: Expert Opin Investig Drugs. 2011 Sep;20(9):1225-41
references: 21740293
references: Clin Cancer Res. 2004 Apr 15;10(8):2659-69
references: 15102668
references: J Urol. 2010 Apr;183(4):1309-15
references: 20171681
references: J Natl Cancer Inst. 1998 Nov 4;90(21):1609-20
references: 9811310
references: Genome Biol. 2001;2(7):REVIEWS3009
references: 11516343
references: Eur Urol. 2010 Jul;58(1):75-83
references: 20359812
references: J Urol. 2005 Mar;173(3):725-8
references: 15711252
references: Lancet Oncol. 2005 Mar;6(3):158-66
references: 15737832
references: J Clin Oncol. 2009 Jul 10;27(20):3312-8
references: 19451442
references: Leukemia. 1999 Feb;13(2):266-74
references: 10025901
references: Eur Urol. 2011 Oct;60(4):644-61
references: 21741163
references: Clin Exp Metastasis. 2007;24(3):149-55
references: 17390110
references: J Mol Med (Berl). 1999 Oct;77(10):699-712
references: 10606205
references: J Clin Oncol. 2009 Aug 1;27(22):3584-90
references: 19487381
references: Eur J Cancer. 2010 Dec;46(18):3141-8
references: 20709527