Drug Resistance Caused by Reversion Mutation

被引：83

作者：

Ashworth, Alan ^{[1
]}

机构：

[1] Inst Canc Res, Chester Beatty Labs, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

来源：

CANCER RESEARCH | 2008年 / 68卷 / 24期

关键词：

D O I：

10.1158/0008-5472.CAN-08-2287

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cells carrying mutated BRCA1 or BRCA2 genes are defective in DNA repair by homologous recombination and, as a consequence, are highly sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP). This provides the basis for a novel "synthetic lethal" approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer. (Cancer Res 2008;68(24):10021-3]

引用

页码：10021 / 10023

页数：3

共 20 条

[1] How do real tumors become resistant to cisplatin? [J].

Borst, Piet ;

Rottenberg, Sven ;

Jonkers, Jos .

CELL CYCLE, 2008, 7 (10) :1353-1359

[2] Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase [J].

Bryant, HE ;

Schultz, N ;

Thomas, HD ;

Parker, KM ;

Flower, D ;

Lopez, E ;

Kyle, S ;

Meuth, M ;

Curtin, NJ ;

Helleday, T .

NATURE, 2005, 434 (7035) :913-917

[3] Improved survival in women with BRCA-associated ovarian carcinoma [J].

Cass, I ;

Baldwin, RL ;

Varkey, T ;

Moslehi, R ;

Narod, SA ;

Karlan, BY .

CANCER, 2003, 97 (09) :2187-2195

[4]

DOBZHANSKY T, 1946, GENETICS, V31, P269

[5] Resistance to therapy caused by intragenic deletion in BRCA2 [J].

Edwards, Stacey L. ;

Brough, Rachel ;

Lord, Christopher J. ;

Natrajan, Rachael ;

Vatcheva, Radost ;

Levine, Douglas A. ;

Boyd, Jeff ;

Reis-Filho, Jorge S. ;

Ashworth, Alan .

NATURE, 2008, 451 (7182) :1111-U8

[6] Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy [J].

Farmer, H ;

McCabe, N ;

Lord, CJ ;

Tutt, ANJ ;

Johnson, DA ;

Richardson, TB ;

Santarosa, M ;

Dillon, KJ ;

Hickson, I ;

Knights, C ;

Martin, NMB ;

Jackson, SP ;

Smith, GCM ;

Ashworth, A .

NATURE, 2005, 434 (7035) :917-921

[7] The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability [J].

Gudmundsdottir, K. ;

Ashworth, A. .

ONCOGENE, 2006, 25 (43) :5864-5874

[8] The concept of synthetic lethality in the context of anticancer therapy [J].

Kaelin, WG .

NATURE REVIEWS CANCER, 2005, 5 (09) :689-698

[9] The resurgence of platinum-based cancer chemotherapy [J].

Kelland, Lloyd .

NATURE REVIEWS CANCER, 2007, 7 (08) :573-584

[10] RAD51, BRCA2 and DNA repair: a partial resolution [J].

Lord, Christopher J. ;

Ashworth, Alan .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2007, 14 (06) :461-462

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