title: Targeted therapy for renal cell carcinoma: The next lap.
abstract: Advances in rationally targeted therapeutics over the last decade have transformed the clinical care of advanced kidney cancer. While oncologists consolidate the gains of the wave of new agents, comprising a panoply of anti-vascular endothelial growth factor multi-targeted tyrosine kinase inhibitors and inhibitors of the mammalian target of rapamycin (mTOR), there is an increasing sense that a plateau has been reached in the short term. It is sobering that all currently approved targeted therapies have not yielded durable remissions and remain palliative in intent. In the context of recent insights in kidney cancer biology, we review promising ongoing and future approaches for kidney cancer therapeutics aimed toward forging new paths in the systemic management of renal cell carcinoma. Broadly, candidate agents for such innovative strategies include immune check-point inhibitors, anti-cancer stem cell agents, next-generation anti-vascular endothelial growth factor receptor and anti-mTOR agents as well as more investigational agents in the preclinical and early clinical development settings.
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Republic of Singapore.
authors.forename: Ravindran
authors.initials: R
authors.lastname: Kanesvaran
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Republic of Singapore ; Institute of Bioengineering and Nanotechnology, Singapore 138669, Republic of Singapore.
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
keywords: Immunotherapy; renal cell carcinoma; targeted therapy; tyrosine kinase inhibitors
references.citation: Lancet Oncol. 2013 May;14(6):552-62
references.pmid: 23598172
references.citation: J Clin Oncol. 2010 Feb 20;28(6):1061-8
references.pmid: 20100962
references.citation: Cancer Immunol Immunother. 2002 May;51(3):171-7
references.pmid: 11941456
references.citation: Nat Genet. 2009 May;41(5):521-3
references.pmid: 19330029
references.citation: Cancer. 2010 Sep 15;116(18):4256-65
references.pmid: 20549832
references.citation: Semin Oncol. 2009 Dec;36 Suppl 3:S3-S17
references.pmid: 19963098
references.citation: Lancet. 2008 Aug 9;372(9637):449-56
references.pmid: 18653228
references.citation: Cancer Res. 2006 Mar 1;66(5):2576-83
references.pmid: 16510575
references.citation: N Engl J Med. 2013 Aug 22;369(8):722-31
references.pmid: 23964934
references.citation: Am J Pathol. 2006 Dec;169(6):2223-35
references.pmid: 17148683
references.citation: Lancet. 2007 Dec 22;370(9605):2103-11
references.pmid: 18156031
references.citation: Am J Surg Pathol. 2013 Oct;37(10):1469-89
references.pmid: 24025519
references.citation: Cancer. 2009 May 15;115(10 Suppl):2313-20
references.pmid: 19402072
references.citation: Am J Physiol Renal Physiol. 2008 Sep;295(3):F680-7
references.pmid: 18614618
references.citation: Science. 1993 May 28;260(5112):1317-20
references.pmid: 8493574
references.citation: Cancer. 2011 Jan 15;117(2):290-300
references.pmid: 20830770
references.citation: Sci Transl Med. 2012 Mar 28;4(127):127ra37
references.pmid: 22461641
references.citation: Cancer. 2012 Dec 15;118(24):6152-61
references.pmid: 22692704
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references.pmid: 12629218
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17174-9
references.pmid: 15569934
references.citation: J Clin Oncol. 1995 Mar;13(3):688-96
references.pmid: 7884429
references.citation: Science. 2013 Mar 29;339(6127):1546-58
references.pmid: 23539594
references.citation: N Engl J Med. 2012 Mar 8;366(10):883-892
references.pmid: 22397650
references.citation: Cancer. 2007 Jun 1;109(11):2257-67
references.pmid: 17440983
references.citation: N Engl J Med. 2012 Jun 28;366(26):2443-54
references.pmid: 22658127
references.citation: Eur J Cancer. 2013 Apr;49(6):1287-96
references.pmid: 23321547
references.citation: Crit Rev Immunol. 2004;24(4):229-37
references.pmid: 15588223
references.citation: Br J Cancer. 2010 May 25;102(11):1592-9
references.pmid: 20461084
references.citation: Leuk Lymphoma. 2001 Nov-Dec;42(6):1195-206
references.pmid: 11911400
references.citation: Oncogene. 2002 Mar 27;21(13):2000-8
references.pmid: 11960372
references.citation: Cancer Cell. 2007 Jul;12(1):9-22
references.pmid: 17613433
references.citation: Clin Cancer Res. 2010 Jan 1;16(1):358-66
references.pmid: 20028764
references.citation: Cancer Res. 2010 Jan 1;70(1):288-98
references.pmid: 20028854
references.citation: FASEB J. 2008 Oct;22(10):3696-705
references.pmid: 18614581
references.citation: Cancer. 2005 Nov 15;104(10):2084-91
references.pmid: 16208700
references.citation: J Clin Oncol. 2013 Oct 20;31(30):3791-9
references.pmid: 24019545
references.citation: Cancer Res. 2011 Aug 1;71(15):5346-56
references.pmid: 21670082
references.citation: Am J Transl Res. 2010 May 20;2(3):296-308
references.pmid: 20589168
references.citation: Nat Genet. 2013 Aug;45(8):860-7
references.pmid: 23797736
references.citation: N Engl J Med. 2007 Jan 11;356(2):115-24
references.pmid: 17215529
references.citation: Nature. 2013 Jul 4;499(7456):43-9
references.pmid: 23792563
references.citation: Target Oncol. 2010 Dec;5(4):269-80
references.pmid: 20563661
references.citation: J Drug Target. 2012 Dec;20(10):873-82
references.pmid: 23050928
references.citation: Br J Cancer. 2004 Mar 8;90(5):985-90
references.pmid: 14997194
references.citation: Invest New Drugs. 2013 Jun;31(3):677-84
references.pmid: 22843211
references.citation: Cancer Invest. 2011 Aug;29(7):451-5
references.pmid: 21696296
references.citation: Cell. 2012 Mar 2;148(5):886-95
references.pmid: 22385958
references.citation: N Engl J Med. 2012 Nov 8;367(19):1783-91
references.pmid: 23020162
references.citation: J Clin Oncol. 2010 May 1;28(13):2137-43
references.pmid: 20368558
references.citation: Cancer Res. 2006 Feb 15;66(4):2328-37
references.pmid: 16489038
references.citation: N Engl J Med. 2007 May 31;356(22):2271-81
references.pmid: 17538086
references.citation: Clin Cancer Res. 2012 Sep 1;18(17):4820-9
references.pmid: 22767667
references.citation: Cancer Res. 2006 Apr 1;66(7):3381-5
references.pmid: 16585157
references.citation: Lancet. 2011 Dec 3;378(9807):1931-9
references.pmid: 22056247
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18030-5
references.pmid: 15596714
references.citation: Clin Cancer Res. 2004 Sep 15;10(18 Pt 2):6315S-21S
references.pmid: 15448024
references.citation: N Engl J Med. 2007 Jan 11;356(2):125-34
references.pmid: 17215530
references.citation: Int J Nephrol. 2011;2011:286985
references.pmid: 21647312
references.citation: J Natl Cancer Inst. 2011 Dec 21;103(24):1884-98
references.pmid: 22043039
references.citation: Cancer Chemother Pharmacol. 2013 May;71(5):1297-307
references.pmid: 23479136
references.citation: Clin Cancer Res. 2010 Jul 15;16(14):3628-38
references.pmid: 20606035
references.citation: Science. 2005 Feb 18;307(5712):1098-101
references.pmid: 15718470
references.citation: Nat Genet. 2012 Jun 10;44(7):751-9
references.pmid: 22683710
references.citation: Nature. 2010 Jan 21;463(7279):360-3
references.pmid: 20054297
references.citation: J Clin Oncol. 2009 Jul 10;27(20):3312-8
references.pmid: 19451442
references.citation: Nat Genet. 2011 Dec 04;44(1):17-9
references.pmid: 22138691
references.citation: Int J Cancer. 2009 Jul 1;125(1):115-23
references.pmid: 19384924
references.citation: J Clin Oncol. 2010 Jul 1;28(19):3167-75
references.pmid: 20516446
references.citation: Int J Cancer. 1986 Oct 15;38(4):489-94
references.pmid: 2428759
references.citation: Cell. 2006 Feb 10;124(3):471-84
references.pmid: 16469695
references.citation: Nature. 2011 Jan 27;469(7331):539-42
references.pmid: 21248752