Cited by 6,683PARP inhibition in cancer therapyDNA Repair MechanismsBRCA gene mutations in cancer

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Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy

Farmer, Hannah, McCabe, Nuala, Lord, Christopher J., Tutt, Andrew N. J., Johnson, Damian A., Richardson, Tobias B., Santarosa, Manuela, Dillon, Krystyna J., Hickson, Ian, Knights, Charlotte, Martin, Niall M. B., Jackson, Stephen P., Smith, Graeme C. M., Ashworth, Alan·2005·Nature

DOI 10.1038/nature03445

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Abstract

BRCA1 and BRCA2 are important for DNA double-strand break repair by homologous recombination, and mutations in these genes predispose to breast and other cancers. Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in base excision repair, a key pathway in the repair of DNA single-strand breaks. We show here that BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis. This seems to be because the inhibition of PARP leads to the persistence of DNA lesions normally repaired by homologous recombination. These results illustrate how different pathways cooperate to repair damage, and suggest that the targeted inhibition of particular DNA repair pathways may allow the design of specific and less toxic therapies for cancer.

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Genome maintenance mechanisms for preventing cancer
Hoeijmakers, J. H. J. (2001) · Nature · doi:10.1038/35077232 · Cited by 3,939
Hallmarks of 'BRCAness' in sporadic cancers
Turner, N. C., Tutt, A. N. J., & Ashworth, A. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1457 · Cited by 1,690
Self-citation
Brca1 Controls Homology-Directed DNA Repair
Moynahan, M. E., Chiu, J. W., Koller, B. H., & Jasin, M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80202-6 · Cited by 1,245
BRCA2 Is Required for Homology-Directed Repair of Chromosomal Breaks
Moynahan, M. E., Pierce, A. J., & Jasin, M. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00174-5 · Cited by 1,007
PARP-2, A Novel Mammalian DNA Damage-dependent Poly(ADP-ribose) Polymerase
Amé, J., Rolli, V., Schreiber, V., Niedergang, C., Apiou, F., Decker, P., Muller, S., Höger, T. H., Murcia, J. M., & de MURCIA, G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.25.17860 · Cited by 744
Breast and Ovarian Cancer
Wooster, R., & Weber, B. (2003) · New England Journal of Medicine · doi:10.1056/nejmra012284 · Cited by 619
The Breast Cancer Susceptibility Gene BRCA1 Is Required for Subnuclear Assembly of Rad51 and Survival following Treatment with the DNA Cross-linking Agent Cisplatin
Bhattacharyya, A., Ear, U., Koller, B. H., Weichselbaum, R. R., & Bishop, D. K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000276200 · Cited by 584
PARP is important for genomic stability but dispensable in apoptosisPreprint
Wang, Z., Stingl, L., Morrison, C. G., Jantsch, M. F., Łoś, M., Schulze‐Osthoff, K., & Wagner, E. F. (1997) · Genes & Development · doi:10.1101/gad.11.18.2347 · Cited by 557
Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes
Furuta, T., Takemura, H., Liao, Z.-Y., Aune, G. J., Redon, C., Sedelnikova, O. A., Pilch, D. R., Rogakou, E. P., Celeste, A., Chen, H. T., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300198200 · Cited by 449

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Dent, R. A., Lindeman, G. J., Clemons, M. J., Wildiers, H. P. M. W., Chan, A., McCarthy, N., Singer, C. F., Lowe, E., Watkins, C. L., & Carmichael, J. (2013) · Breast Cancer Research · doi:10.1186/bcr3484 · Cited by 186
Phase I/Ib Study of Olaparib and Carboplatin in BRCA1 or BRCA2 Mutation-Associated Breast or Ovarian Cancer With Biomarker Analyses
Lee, J.-M., Hays, J. L., Annunziata, C. M., Noonan, A. M., Minasian, L. M., Zujewski, J. A., Yu, M., Gordon, N., Ji, J. J., Sissung, T. M., et al. (2014) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dju089 · Cited by 185
Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule
Zhao, Q., Lan, T., Su, S., & Rao, Y. (2018) · Chemical Communications · doi:10.1039/c8cc07813k · Cited by 187
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Alexandrov, L. B., Nik‐Zainal, S., Siu, H. C., Leung, S. Y., & Stratton, M. R. (2015) · Nature Communications · doi:10.1038/ncomms9683 · Cited by 178
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Drew, Y., Zenke, F. T., & Curtin, N. J. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01060-w · Cited by 208
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Wang, B., Chu, D., Feng, Y., Shen, Y., Aoyagi-Scharber, M., & Post, L. E. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01498 · Cited by 186
Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer
Rojo, F., García-Parra, J., Zazo, S., Tusquets, I., Ferrer-Lozano, J., Menéndez, S., Eroles, P., Chamizo, C., Servitja, S., Ramírez-Merino, N., et al. (2011) · Annals of Oncology · doi:10.1093/annonc/mdr361 · Cited by 184
PARP inhibitors: its role in treatment of cancer
Chen, A. P. (2011) · 癌症：英文版 · doi:10.5732/cjc.011.10111 · Cited by 182
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Wang, B., & Lee, N. (2018) · Cancers · doi:10.3390/cancers10110458 · Cited by 183
m5C modification of mRNA serves a DNA damage code to promote homologous recombination
Chen, H., Yang, H., Zhu, X., Yadav, T., Ouyang, J., Truesdell, S. S., Tan, J. J., Wang, Y., Duan, M.-H., Wei, L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16722-7 · Cited by 189
PARP inhibitors: New partners in the therapy of cancer and inflammatory diseases
Peralta-Leal, A., Rodríguez-Vargas, J. M., Aguilar‐Quesada, R., Rodríguez, M. I., Linares, J. L., de Almodóvar, M. R., & Oliver, F. J. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.04.008 · Cited by 189
The Role of Chromosomal Instability in Cancer and Therapeutic Responses
Vargas-Rondón, N., Villegas, V. E., & Rondón‐Lagos, M. (2017) · Cancers · doi:10.3390/cancers10010004 · Cited by 187
PARP Inhibition in Cancer: An Update on Clinical Development
Sachdev, E., Tabatabai, R., Roy, V. Y., Rimel, B. J., & Mita, M. M. (2019) · Targeted Oncology · doi:10.1007/s11523-019-00680-2 · Cited by 190
Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM-deficient cancer cells
Lloyd, R. L., Wijnhoven, P. W. G., Ramos‐Montoya, A., Wilson, Z., Illuzzi, G., Falenta, K., Jones, G. N., James, N. H., Chabbert, C. D., Stott, J., et al. (2020) · Oncogene · doi:10.1038/s41388-020-1328-y · Cited by 185
Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation
Topatana, W., Juengpanich, S., Li, S., Cao, J., Hu, J., Lee, J., Suliyanto, K., Ma, D., Zhang, B., Chen, M., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00956-5 · Cited by 193
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Stewart, E. A., Goshorn, D. R., Bradley, C. L., Griffiths, L. M., Benavente, C. A., Twarog, N. R., Miller, G. M., Caufield, W. V., Freeman, B. B., Bahrami, A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.09.028 · Cited by 183
The DNA Damaging Revolution: PARP Inhibitors and Beyond
Yap, T. A., Plummer, R., Azad, N. S., & Helleday, T. (2019) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_238473 · Cited by 178
Poly ADP-ribose polymerase-1: An international molecule of mystery
Woodhouse, B. C., & Dianov, G. L. (2008) · DNA repair · doi:10.1016/j.dnarep.2008.03.009 · Cited by 181
Plk1 and CK2 Act in Concert to Regulate Rad51 during DNA Double Strand Break Repair
Yata, K., Lloyd, J., Maslen, S., Bleuyard, J., Skehel, M. J., Smerdon, S. J., & Esashi, F. (2012) · Molecular Cell · doi:10.1016/j.molcel.2011.12.028 · Cited by 187
A high-throughput RNA interference screen for DNA repair determinants of PARP inhibitor sensitivity
Lord, C. J., McDonald, S., Swift, S., Turner, N. C., & Ashworth, A. (2008) · DNA repair · doi:10.1016/j.dnarep.2008.08.014 · Cited by 177
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Min, A., Im, S., Kim, D. K., Song, S., Kim, H. J., Lee, K.-H., Kim, T., Han, S., Oh, D., Kim, T., et al. (2015) · Breast Cancer Research · doi:10.1186/s13058-015-0534-y · Cited by 180
Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition
Aguilar‐Quesada, R., Muñoz‐Gámez, J. A., Martín‐Oliva, D., Peralta, A., Valenzuela, M. T., Matínez-Romero, R., Quiles, R., Murcia, J. M., de MURCIA, G., de Almodóvar, J. M. R., et al. (2007) · BMC Molecular Biology · doi:10.1186/1471-2199-8-29 · Cited by 186
PARP inhibitors in ovarian cancer: Sensitivity prediction and resistance mechanisms
Jiang, X., Li, X., Li, W., Bai, H., & Zhang, Z. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14133 · Cited by 179
Platinum Antitumor Complexes: 50 Years Since Barnett Rosenberg's Discovery
Muggia, F. M., Bonetti, A. V., Hoeschele, J. D., Rozencweig, M., & Howell, S. B. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.60.7481 · Cited by 181
Small Interfering RNA Screens Reveal Enhanced Cisplatin Cytotoxicity in Tumor Cells Having both BRCA Network and TP53 Disruptions
Bartz, S. R., Zhang, Z., Burchard, J., Imakura, M., Martin, M. M., Palmieri, A., Needham, R. H. V., Guo, J., Gordon, M. L., Chung, N., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01229-06 · Cited by 178
DNA repair deficiency as a therapeutic target in cancer
Martin, S. A., Lord, C. J., & Ashworth, A. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.01.016 · Cited by 176
Self-citation
RAD51 Up-regulation Bypasses BRCA1 Function and Is a Common Feature of BRCA1 -Deficient Breast Tumors
Martin, R. W., Orelli, B. J., Yamazoe, M., Minn, A. J., Takeda, S., & Bishop, D. K. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0290 · Cited by 177
Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors
Balmañà, J., Tung, N., Isakoff, S. J., Graña, B., Ryan, P. J., Saura, C., Lowe, E., Frewer, P., Winer, E. P., Baselga, J. M., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu187 · Cited by 177

Authors: Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., Martin, N. M. B., Jackson, S. P., Smith, G. C. M., & Ashworth, A.
Affiliations: Cancer Research UK (GB)
Institute of Cancer Research (GB)
Guy's Hospital (GB)
University of Cambridge (GB)
Corresponding author: Smith, Graeme C. M.
Ashworth, Alan
ORCID: Lord, Christopher J.
Tutt, Andrew N. J.
Santarosa, Manuela
Hickson, Ian
Martin, Niall M. B.
Jackson, Stephen P.
Smith, Graeme C. M.
Ashworth, Alan
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2005-04
Volume: 434
Issue: 7035
Pages: 917-921
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature03445
OpenAlex: W1973268287
Cited by: 6,683
References: 24
Citations by year: 2026: 271 · 2025: 346 · 2024: 356 · 2023: 454 · 2022: 443 · 2021: 502 · 2020: 460 · 2019: 382 · 2018: 381 · 2017: 353 · 2016: 358 · 2015: 315 · 2014: 312 · 2013: 292 · 2012: 262
FWCI: 68.30
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: Cancer Research UK
National Cancer Institute (F31CA260794)
Topics: Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Keywords: BRCA1, BRCA2, PARP inhibitors, homologous recombination, base excision repair, synthetic lethality, breast cancer, DNA double-strand break repair, chromosomal instability, cell cycle arrest, apoptosis, targeted cancer therapy
MeSH terms: Poly(ADP-ribose) Polymerase Inhibitors, Animals, Antineoplastic Agents, Cell Survival, DNA Damage, DNA Repair, Mice, Nude, Models, Biological, Mutation, Neoplasms, Poly(ADP-ribose) Polymerases, Substrate Specificity, Apoptosis, Genes, BRCA1, Xenograft Model Antitumor Assays, Genes, BRCA2, Mice

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Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy

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