Emergence of rationally designed therapeutic strategies for breast cancer targeting DNA repair mechanisms.
Accumulating evidence suggests that many cancers, including BRCA1- and BRCA2-associated breast cancers, are deficient in DNA repair processes. Both hereditary and sporadic breast cancers have been found to have significant downregulation of repair factors. This has provided opportunities to exploit DNA repair deficiencies, whether acquired or inherited. Here, we review efforts to exploit DNA repair deficiencies in tumors, with a focus on breast cancer. A variety of agents, including PARP (poly [ADP-ribose] polymerase) inhibitors, are currently under investigation in clinical trials and available results will be reviewed.
Rowe
Bryan P
BP
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040, USA. bryan.rowe@yale.edu
Glazer
Peter M
PM
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002986:Clinical Trials as Topic; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D007211:Indoles; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C521013:veliparib; C531549:rucaparib; D011065:Poly(ADP-ribose) Polymerases
Cancer Res. 2009 Feb 1;69(3):1221-9
19141645
Cancer Res. 2008 Jan 15;68(2):605-14
18199558
J Biol Chem. 2000 Aug 4;275(31):23899-903
10843985
Cell. 2002 May 17;109(4):459-72
12086603
Oncogene. 2002 Dec 16;21(58):8949-56
12483511
Annu Rev Genet. 2009;43:223-49
19686080
Cancer Invest. 2009 Aug;27(7):756-63
19440934
DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1103-8
15279798
Mol Cancer Res. 2009 Aug;7(8):1304-9
19671671
Br J Cancer. 2001 Jan 5;84(1):106-12
11139322
Clin Cancer Res. 2009 Mar 15;15(6):1853-9
19240165
Am J Clin Oncol. 1998 Aug;21(4):355-61
9708633
DNA Repair (Amst). 2009 Sep 2;8(9):1153-65
19501553
Mutagenesis. 2006 May;21(3):173-8
16613912
Clin Cancer Res. 2007 May 1;13(9):2728-37
17473206
Biochem Soc Trans. 2006 Nov;34(Pt 5):633-45
17052168
J Natl Cancer Inst. 2004 Jan 7;96(1):56-67
14709739
Mol Cancer Ther. 2007 Aug;6(8):2290-302
17699724
J Clin Oncol. 2007 Apr 10;25(11):1329-33
17416853
Nature. 2005 Feb 10;433(7026):653-7
15703751
Cell. 2002 Nov 1;111(3):393-405
12419249
N Engl J Med. 2009 Jul 9;361(2):189-91
19553640
Cancer Lett. 2005 Jun 1;223(1):143-50
15890247
Hum Mol Genet. 2002 Oct 1;11(21):2531-46
12354779
Nat Med. 2003 May;9(5):568-74
12692539
Mol Cancer Ther. 2006 Apr;5(4):952-61
16648566
Cancer Res. 2006 Aug 15;66(16):8109-15
16912188
Nature. 2004 Nov 18;432(7015):316-23
15549093
Mol Cell. 2001 Feb;7(2):249-62
11239454
Mol Cancer Res. 2008 Oct;6(10):1621-9
18922977
Nature. 2005 Apr 14;434(7035):917-21
15829967
Clin Cancer Res. 2004 Feb 1;10(3):881-9
14871963
Semin Radiat Oncol. 2006 Jan;16(1):51-8
16378907
N Engl J Med. 2009 Jul 9;361(2):123-34
19553641
Cancer Res. 2005 Dec 15;65(24):11597-604
16357170
Cancer. 2003 May 1;97(9):2187-95
12712470
Cancer Lett. 2004 Mar 18;205(2):155-60
15036647
Cancer Res. 2010 Jan 1;70(1):409-17
20028873
J Biomed Biotechnol. 2009;2009:369129
19644562
Clin Cancer Res. 2008 Dec 1;14(23):7917-23
19047122
Nature. 2000 Nov 23;408(6811):429-32
11100717
Oncogene. 2002 Dec 16;21(58):8981-93
12483514
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7303-7
9207086
Nature. 2005 Apr 14;434(7035):913-7
15829966
Cancer Res. 2007 Aug 1;67(15):7078-81
17671173
Cancer Res. 2005 Sep 15;65(18):8134-41
16166287
Cell Mol Life Sci. 2009 Mar;66(6):981-93
19153658
Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2201-6
20133863
Cancer Gene Ther. 2004 Aug;11(8):539-46
15192709
Genes Dev. 2004 Aug 15;18(16):1958-63
15314022
Cold Spring Harb Symp Quant Biol. 2005;70:139-48
16869747
Clin Cancer Res. 2007 Mar 1;13(5):1532-9
17332299
Mol Cell. 2005 Mar 18;17(6):793-803
15780936
Cancer Res. 1999 Apr 1;59(7 Suppl):1752s-1756s
10197592
Cancer Treat Rev. 2003 Aug;29(4):297-307
12927570
Cancer Res. 2000 Sep 1;60(17):4889-93
10987303
Radiother Oncol. 2008 Aug;88(2):258-68
18456354
Cancer Metastasis Rev. 2007 Jun;26(2):249-60
17415527
Mol Cell. 1998 May;1(6):783-93
9660962
Mol Cell. 1999 Oct;4(4):511-8
10549283
Mol Cell Biol. 2003 May;23(9):3265-73
12697826
Nat Rev Drug Discov. 2005 May;4(5):421-40
15864271
Hum Pathol. 2008 May;39(5):672-80
18329696
Mol Cell Biol. 2004 Oct;24(19):8504-18
15367671
Nature. 2008 Feb 28;451(7182):1111-5
18264088
Histopathology. 2008 May;52(6):698-705
18393977
J Biol Chem. 2002 Jun 21;277(25):23028-36
11948190
Nat Rev Cancer. 2005 Sep;5(9):689-98
16110319
Clin Cancer Res. 2007 May 15;13(10):3033-42
17505006
Cancer Res. 2008 Apr 15;68(8):2581-6
18413725
Br J Cancer. 1999 Mar;79(7-8):1012-7
10098729
Nat Rev Cancer. 2004 Oct;4(10):814-9
15510162
Mol Cancer Ther. 2003 Apr;2(4):371-82
12700281
Nature. 2008 Feb 28;451(7182):1116-20
18264087
Cancer Res. 1997 Nov 15;57(22):5143-7
9371516
Mol Cell Biol. 2000 Nov;20(21):8283-9
11027296
Cell Mol Life Sci. 2009 Mar;66(6):1039-56
19153654
Mol Cancer Ther. 2005 Sep;4(9):1364-8
16170028
Clin Cancer Res. 2000 Jul;6(7):2860-7
10914735
Neoplasia. 2008 Nov;10(11):1222-30
18953431
Clin Cancer Res. 2007 Mar 1;13(5):1383-8
17332279
J Clin Oncol. 2007 Sep 10;25(26):4066-74
17827455