Mouse models of advanced spontaneous metastasis for experimental therapeutics.
An enduring problem in cancer research is the failure to reproduce highly encouraging preclinical therapeutic findings using transplanted or spontaneous primary tumours in mice in clinical trials of patients with advanced metastatic disease. There are several reasons for this, including the failure to model established, visceral metastatic disease. We therefore developed various models of aggressive multi-organ spontaneous metastasis after surgical resection of orthotopically transplanted human tumour xenografts. In this Opinion article we provide a personal perspective summarizing the prospect of their increased clinical relevance. This includes the reduced efficacy of certain targeted anticancer drugs, the late emergence of spontaneous brain metastases and the clinical trial results evaluating a highly effective therapeutic strategy previously tested using such models.
The Molecular & Cellular Biology Research, Sunnybrook Health Science Centre, Toronto, Ontario M4N 3M5, Canada. giulio.francia@sunnybrook.ca
Giulio
G
Francia
William
W
Cruz-Munoz
Shan
S
Man
Ping
P
Xu
Robert S
RS
Kerbel
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents
N Engl J Med. 2004 Jun 3;350(23):2335-42
15175435
Clin Exp Metastasis. 1984 Jan-Mar;2(1):15-36
6085722
Cancer Res. 1990 Feb 1;50(3):717-21
2297709
Cancer Res. 1980 May;40(5):1636-44
7370995
Cancer Res. 1984 Aug;44(8):3522-9
6744277
Cancer Metastasis Rev. 1990 Feb;8(4):285-97
2182209
Clin Exp Metastasis. 1984 Oct-Dec;2(4):297-310
6543707
Cancer Res. 2002 May 15;62(10):2731-5
12019144
Cancer Res. 1988 Apr 1;48(7):1943-8
3349467
Cancer Res. 2005 Apr 15;65(8):3396-403
15833874
Br J Cancer. 1989 Feb;59(2):179-83
2930682
Cancer Res. 2006 Apr 1;66(7):3386-91
16585158
Cancer Chemother Pharmacol. 1997;40(1):87-93
9137536
J Clin Invest. 2003 May;111(9):1287-95
12727920
Clin Cancer Res. 2009 Jul 15;15:4529
25278743
Int J Cancer. 1992 Aug 19;52(1):98-104
1500231
Nat Biotechnol. 2010 Jun;28(6):585-93
20495549
Am J Pathol. 2007 Mar;170(3):793-804
17322365
PLoS One. 2009 Sep 03;4(9):e6896
19727403
Clin Cancer Res. 2009 Oct 1;15(19):6148-57
19789319
Nature. 2005 Jul 28;436(7050):518-24
16049480
Science. 2009 Jun 12;324(5933):1457-61
19460966
Nat Med. 2000 Jun;6(6):711-4
10835692
Cancer Cell. 2009 Jul 7;16(1):67-78
19573813
Ann Oncol. 2005 Nov;16(11):1846-7
15972278
J Cell Biochem. 1994 Sep;56(1):16-22
7806587
Clin Exp Metastasis. 1997 May;15(3):272-306
9174129
Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):904-16
16467105
Cancer Res. 2006 Oct 1;66(19):9787
17018641
Cancer Res. 2008 Jun 15;68(12):4500-5
18559492
J Clin Oncol. 2010 May 20;28(15):2505-11
20406939
Nat Rev Drug Discov. 2006 Sep;5(9):741-54
16915232
Biochem Biophys Res Commun. 2010 Apr 9;394(3):443-7
20230796
J Natl Cancer Inst. 2008 Aug 6;100(15):1092-103
18664652
Cancer Cell. 2009 Mar 3;15(3):220-31
19249680
Eur J Cancer. 2004 Apr;40(6):837-44
15120039
J Natl Cancer Inst. 1984 Jan;72(1):93-108
6582307
Cancer Res. 2000 Jul 1;60(13):3605-11
10910075
Clin Exp Metastasis. 1998 Nov;16(8):751-6
10211988
Int J Cancer. 2007 Mar 15;120(6):1284-92
17163422
Nat Rev Cancer. 2007 Oct;7(10):737-49
17891189
Carcinogenesis. 2005 Mar;26(3):513-23
15358632
PLoS One. 2009 Jun 10;4(6):e5857
19516901
Nature. 2009 Sep 17;461(7262):E4; discussion E5
19759568
Nat Clin Pract Oncol. 2008 Apr;5(4):206-19
18253104
Science. 2006 May 26;312(5777):1171-5
16728631
Clin Cancer Res. 2007 Mar 15;13(6):1648-55
17363517
N Engl J Med. 2007 Jul 5;357(1):39-51
17611206
Breast Cancer Res Treat. 2006 Mar;96(2):101-13
16319986
J Clin Invest. 1995 Apr;95(4):1789-97
7535799
Nat Med. 2010 Sep;16(9):976-7
20823881
J Clin Oncol. 2008 Oct 20;26(30):4899-905
18794539
Nat Rev Cancer. 2010 Jul;10(7):470-80
20574449
Cell. 2002 Jan 25;108(2):135-44
11832204
Nature. 2009 Jun 18;459(7249):1005-9
19421193
Clin Cancer Res. 2009 Aug 1;15(15):4867-74
19622578
Cancer Res. 1993 Jul 1;53(13):3070-2
8319214
Mol Cancer Ther. 2008 Oct;7(10):3452-9
18852148
Cancer Cell. 2003 Jun;3(6):537-49
12842083
Clin Cancer Res. 2009 Oct 15;15(20):6358-66
19825954
Cancer Biol Ther. 2003 Jul-Aug;2(4 Suppl 1):S134-9
14508091
Nat Biotechnol. 2010 Jun;28(6):561-2
20531333
Cancer Metastasis Rev. 1998-1999;17(3):301-4
10352884
Int J Cancer. 1994 Jun 15;57(6):920-5
7515861
Science. 1982 Sep 10;217(4564):998-1003
7112116
J Clin Invest. 2005 Jan;115(1):44-55
15630443
Oncogene. 2001 Nov 8;20(51):7514-23
11709723
Cancer Metastasis Rev. 2007 Dec;26(3-4):737-47
17846863
J Natl Cancer Inst. 2002 Dec 18;94(24):1854-62
12488479
Clin Exp Metastasis. 2009;26(4):345-55
18787963
Cancer Control. 2005 Oct;12(4):236-41
16258495
J Cell Biochem. 1994 Sep;56(1):4-8
7806591