Cited by 5,198PARP inhibition in cancer therapyDNA Repair MechanismsBRCA gene mutations in cancer

The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.

Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase

Open access

Bryant, Helen E., Schultz, Niklas, Thomas, Huw D., Parker, Kayan M., Flower, Dan, Lopez, Elena, Kyle, Suzanne, Meuth, Mark, Curtin, Nicola J., Helleday, Thomas·2005·Nature

DOI 10.1038/nature03443

Open this paper in CoChat — free account

Abstract

Poly(ADP-ribose) polymerase (PARP1) facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Nevertheless, PARP1-/- mice are viable, fertile and do not develop early onset tumours. Here, we show that PARP inhibitors trigger gamma-H2AX and RAD51 foci formation. We propose that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair. Furthermore, we show that BRCA2-deficient cells, as a result of their deficiency in homologous recombination, are acutely sensitive to PARP inhibitors, presumably because resultant collapsed replication forks are no longer repaired. Thus, PARP1 activity is essential in homologous recombination-deficient BRCA2 mutant cells. We exploit this requirement in order to kill BRCA2-deficient tumours by PARP inhibition alone. Treatment with PARP inhibitors is likely to be highly tumour specific, because only the tumours (which are BRCA2-/-) in BRCA2+/- patients are defective in homologous recombination. The use of an inhibitor of a DNA repair enzyme alone to selectively kill a tumour, in the absence of an exogenous DNA-damaging agent, represents a new concept in cancer treatment.

Integrity signals

Registry

Crossref · 10.1038/nature03443

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
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., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683
Instability and decay of the primary structure of DNA
Lindahl, T. (1993) · Nature · doi:10.1038/362709a0 · Cited by 5,679
A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., & Bonner, W. M. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00610-2 · Cited by 2,098
Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions
D’Amours, D., Desnoyers, S., D’Silva, I., & Poirier, G. G. (1999) · Biochemical Journal · doi:10.1042/bj3420249 · Cited by 1,819
Cancer Susceptibility and the Functions of BRCA1 and BRCA2
Venkitaraman, A. R. (2002) · Cell · doi:10.1016/s0092-8674(02)00615-3 · Cited by 1,713
Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells
Murcia, J. M., Niedergang, C., Trucco, C., Ricoul, M., Dutrillaux, B., Mark, M. P., Oliver, F. J., Masson, M., Dierich, A., LeMeur, M., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7303 · Cited by 1,058
A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage
El‐Khamisy, S. F. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg761 · Cited by 689
Functional interaction between PARP‐1 and PARP‐2 in chromosome stability and embryonic development in mouse
Murcia, J. M., Ricoul, M., Tartier, L., Niedergang, C., Huber, A., Dantzer, F., Schreiber, V., Amé, J., Dierich, A., LeMeur, M., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg206 · Cited by 629
Post-translational modification of poly(ADP-ribose) polymerase induced by DNA strand breaks
Lindahl, T. L., Satoh, M. S., Poirier, G. G., & Klungland, A. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89089-1 · Cited by 611
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

Show all 26 references

Sorted by citations

Items 301–400 of 1,021

Oxidatively induced DNA damage and its repair in cancer
Dizdaroğlu, M. (2014) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2014.11.002 · Cited by 264
PARP inhibitors in pancreatic cancer: molecular mechanisms and clinical applications
Zhu, H., Wei, M., Xu, J., Hua, J., Chen, L., Meng, Q., Zhang, Y., Liu, J., Zhang, B., Yu, X., et al. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01167-9 · Cited by 263
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers
Redon, C. E., Nakamura, A., Zhang, Y., Ji, J. J., Bonner, W. M., Kinders, R. J., Parchment, R. E., Doroshow, J. H., & Pommier, Y. G. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0523 · Cited by 262
Ataxia Telangiectasia Mutated (ATM) Signaling Network Is Modulated by a Novel Poly(ADP-ribose)-dependent Pathway in the Early Response to DNA-damaging Agents
Haince, J.-F., Kozlov, S., Dawson, V. L., Dawson, T. M., Hendzel, M. J., Lavin, M. F., & Poirier, G. G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608406200 · Cited by 261
Human Apurinic/Apyrimidinic Endonuclease 1
Li, M., & Wilson, D. M. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5492 · Cited by 261
New Paradigms and Future Challenges in Radiation Oncology: An Update of Biological Targets and Technology
Liauw, S. L., Connell, P. P., & Weichselbaum, R. R. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005148 · Cited by 260
Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas
Kummar, S., Chen, A., Ji, J., Zhang, Y., Reid, J. M., Ames, M., Jia, L., Weil, M., Speranza, G., Murgo, A. J., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1227 · Cited by 259
Homologous recombination deficiency and ovarian cancer
Ledermann, J. A., Drew, Y., & Kristeleit, R. S. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2016.03.005 · Cited by 258
High-content CRISPR screening
Bock, C., Datlinger, P., Chardon, F. M., Coelho, M. A., Dong, M. B., Lawson, K. A., Lu, T., Maroc, L., Norman, T. M., Song, B., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00098-7 · Cited by 264
Oncogene addiction as a foundational rationale for targeted anti‐cancer therapy: promises and perils
Torti, D., & Trusolino, L. (2011) · EMBO Molecular Medicine · doi:10.1002/emmm.201100176 · Cited by 257
Human AP endonuclease 1 (APE1): From mechanistic insights to druggable target in cancer
Abbotts, R., & Madhusudan, S. (2010) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2009.12.006 · Cited by 256
PCAT-1 , a Long Noncoding RNA, Regulates BRCA2 and Controls Homologous Recombination in Cancer
Prensner, J. R., Chen, W., Iyer, M. K., Cao, Q., Ma, T., Han, S., Sahu, A., Malik, R., Wilder-Romans, K., Navone, N. M., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3159 · Cited by 255
Two decades beyond BRCA1/2: Homologous recombination, hereditary cancer risk and a target for ovarian cancer therapy
Walsh, C. (2015) · Gynecologic Oncology · doi:10.1016/j.ygyno.2015.02.017 · Cited by 254
The expanding universe of PARP1-mediated molecular and therapeutic mechanisms
Huang, D., & Kraus, W. L. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.02.021 · Cited by 254
Niraparib activates interferon signaling and potentiates anti-PD-1 antibody efficacy in tumor models
Wang, Z., Sun, K., Xiao, Y., Feng, B., Mikule, K., Ma, X., Feng, N., Vellano, C. P., Federico, L., Marszalek, J. R., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-38534-6 · Cited by 253
BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair
Bunting, S. F., Callén, E., Kozak, M. L., Kim, J. M., Wong, N., López-Contreras, A. J., Ludwig, T., Baer, R., Faryabi, R. B., Malhowski, A., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.02.015 · Cited by 252
Blocking c-Met–mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors
Du, Y., Yamaguchi, H., Wei, Y., Hsu, J. L., Wang, H.-L., Hsu, Y.-H., Lin, W.-C., Yu, W.-H., Leonard, P. G., Lee, G. R., et al. (2016) · Nature Medicine · doi:10.1038/nm.4032 · Cited by 252
A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics
Chaikuad, A., Tacconi, E. M., Zimmer, J., Liang, Y., Gray, N. S., Tarsounas, M., & Knapp, S. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1629 · Cited by 250
Contextual Synthetic Lethality of Cancer Cell Kill Based on the Tumor Microenvironment
Chan, N. H. L., Pires, I. M., Bencokova, Z., Coackley, C. L., Luoto, K. R., Bhogal, N., Lakshman, M., Gottipati, P., Oliver, F. J., Helleday, T., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2352 · Cited by 250
Self-citation
Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone
Damiani, R. M., Moura, D. J., Viau, C. M., Caceres, R. A., Henriques, J. A. P., & Saffi, J. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1759-y · Cited by 250
Repair of DNA double-strand breaks by mammalian alternative end-joining pathways
Sallmyr, A., & Tomkinson, A. E. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.tm117.000375 · Cited by 250
A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2 -Mutated Ovarian Carcinoma or Other Solid Tumors
Kristeleit, R. S., Shapiro, G. I., Burris, H. A., Oza, A. M., LoRusso, P. M., Patel, M. R., Domchek, S. M., Balmañà, J., Drew, Y., Chen, L.-M., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2796 · Cited by 248
Triple-negative breast cancer
Chacon, R. D., & Costanzo, M. V. (2010) · Breast Cancer Research · doi:10.1186/bcr2574 · Cited by 247
DNA Repair in Prostate Cancer: Biology and Clinical Implications
Mateo, J., Boysen, G., Barbieri, C. E., Bryant, H. E., Castro, E., Nelson, P., Olmos, D., Pritchard, C. C., Rubin, M. A., & Bono, J. S. D. (2016) · European Urology · doi:10.1016/j.eururo.2016.08.037 · Cited by 247
Self-citation
Beyond DNA Repair: Additional Functions of PARP-1 in Cancer
Weaver, A. N., & Yang, E. S. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00290 · Cited by 246
A review of PARP inhibitors: from bench to bedside
Underhill, C. R., Toulmonde, M., & Bonnefoi, H. R. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq322 · Cited by 246
Applying Synthetic Lethality for the Selective Targeting of Cancer
McLornan, D. P., List, A. F., & Mufti, G. J. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1407390 · Cited by 246
Repression of BET activity sensitizes homologous recombination–proficient cancers to PARP inhibition
Yang, L., Zhang, Y., Shan, W., Hu, Z., Yuan, J., Pi, J., Wang, Y., Fan, L., Tang, Z., Li, C., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aal1645 · Cited by 246
Combined PARP Inhibition and Immune Checkpoint Therapy in Solid Tumors
Peyraud, F., & Italiano, A. (2020) · Cancers · doi:10.3390/cancers12061502 · Cited by 245
53BP1: a DSB escortPreprint
Mirman, Z., & de Lange, T. (2020) · Genes & Development · doi:10.1101/gad.333237.119 · Cited by 248
Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy
Kim, B. M., Hong, Y., Lee, S., Liu, P., Lim, J. Y., Lee, Y. C., Lee, T., Chang, K. T., & Hong, Y. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161125991 · Cited by 243
HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination
Adimoolam, S., Sirisawad, M., Chen, J., Thiemann, P., Ford, J. M., & Buggy, J. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707828104 · Cited by 242
Inhibition of Homologous Recombination by the PCNA-Interacting Protein PARI
Moldovan, G., Dejsuphong, D., Petalcorin, M. I. R., Hofmann, K., Takeda, S., Boulton, S. J., & D’Andrea, A. D. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.11.010 · Cited by 242
Exploiting DNA Replication Stress for Cancer Treatment
Ubhi, T., & Brown, G. W. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3631 · Cited by 245
Overcoming drug resistance in pancreatic cancer
Long, J., Zhang, Y., Yu, X., Yang, J., LeBrun, D. G., Chen, C., Yao, Q. C., & Li, M. (2011) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.566216 · Cited by 241
Development of PARP and immune-checkpoint inhibitor combinations
Stewart, R. A., Pilié, P. G., & Yap, T. A. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-2652 · Cited by 239
p53 as a target for the treatment of cancer
Duffy, M. J., Synnott, N. C., McGowan, P. M., Crown, J. P., O’Connor, D. P., & Gallagher, W. M. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.10.004 · Cited by 239
Role of BRCA Mutations in Cancer Treatment with Poly(ADP-ribose) Polymerase (PARP) Inhibitors
Faraoni, I., & Graziani, G. (2018) · Cancers · doi:10.3390/cancers10120487 · Cited by 239
Biomarker-Guided Development of DNA Repair Inhibitors
Cleary, J. M., Aguirre, A. J., Shapiro, G. I., & D’Andrea, A. D. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.04.035 · Cited by 239
Recent therapeutic trends and promising targets in triple negative breast cancer
Hwang, S., Park, S., & Kwon, Y. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.006 · Cited by 239
Mismatch repair deficient colorectal cancer in the era of personalized treatment
Hewish, M., Lord, C. J., Martin, S. A., Cunningham, D., & Ashworth, A. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.18 · Cited by 236
The role of BRCA1 in DNA damage response
Wu, J., Lu, L.-Y., & Yu, X. (2010) · Protein & Cell · doi:10.1007/s13238-010-0010-5 · Cited by 235
Rational combination therapy with PARP and MEK inhibitors capitalizes on therapeutic liabilities in RAS mutant cancers
Sun, C., Fang, Y., Yin, J., Chen, J., Ju, Z., Zhang, D., Chen, X., Vellano, C. P., Jeong, K. J., Ng, P. K., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aal5148 · Cited by 237
PTEN Loss Compromises Homologous Recombination Repair in Astrocytes: Implications for Glioblastoma Therapy with Temozolomide or Poly(ADP-Ribose) Polymerase Inhibitors
Mcellin, B. M., Camacho, C. V., Mukherjee, B., Hahm, B., Tomimatsu, N., Bachoo, R. M., & Burma, S. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4295 · Cited by 234
Synthetic Lethality — A New Direction in Cancer-Drug Development
Iglehart, J. D., & Silver, D. P. (2009) · New England Journal of Medicine · doi:10.1056/nejme0903044 · Cited by 234
Killing cells by targeting mitosis
Manchado, E., Guillamot, M., & Malumbres, M. (2012) · Cell Death and Differentiation · doi:10.1038/cdd.2011.197 · Cited by 233
Poly(ADP-Ribose) Polymerase Is Hyperactivated in Homologous Recombination–Defective Cells
Gottipati, P., Vischioni, B., Schultz, N., Solomons, J., Bryant, H. E., Djureinovic, T., Issaeva, N., Sleeth, K. M., Sharma, R. A., & Helleday, T. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4716 · Cited by 233
Self-citation
Targeting tumour-supportive cellular machineries in anticancer drug development
Dobbelstein, M., & Moll, U. M. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4201 · Cited by 233
Genome-wide transcriptome profiling of homologous recombination DNA repair
Peng, G., Lin, C. C.-J., Mo, W., Dai, H., Park, Y., Kim, S. M., Peng, Y., Mo, Q., Siwko, S. K., Hu, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms4361 · Cited by 231
Nuclear ADP-Ribosylation and Its Role in Chromatin Plasticity, Cell Differentiation, and Epigenetics
Hottiger, M. O. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034506 · Cited by 231
Trapping Poly(ADP-Ribose) Polymerase
Shen, Y., Aoyagi-Scharber, M., & Wang, B. (2015) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.222448 · Cited by 230
Unraveling the mechanism of BRCA2 in homologous recombination
Holloman, W. K. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2096 · Cited by 230
DNA Double-Strand Break Repair Inhibitors as Cancer Therapeutics
Srivastava, M., & Raghavan, S. C. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.11.013 · Cited by 230
Differential Phosphorylation of DNA-PKcs Regulates the Interplay between End-Processing and End-Ligation during Nonhomologous End-Joining
Jiang, W., Crowe, J. L., Liu, X., Nakajima, S., Wang, Y., Li, C., Lee, B. J., Dubois, R. L., Liu, C., Yu, X., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.024 · Cited by 229
Error-prone translesion synthesis mediates acquired chemoresistance
Xie, K., Doles, J. D., Hemann, M. T., & Walker, G. C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1011412107 · Cited by 228
PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: current practice and future directions
Konecny, G. E., & Kristeleit, R. S. (2016) · British Journal of Cancer · doi:10.1038/bjc.2016.311 · Cited by 228
BRCA1/2 testing: therapeutic implications for breast cancer management
Tung, N., & Garber, J. E. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0127-5 · Cited by 228
Platinum compounds 30 years after the introduction of cisplatin: Implications for the treatment of ovarian cancer
Muggia, F. M. (2008) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.09.034 · Cited by 227
LEDGF (p75) promotes DNA-end resection and homologous recombination
Daugaard, M., Baude, A., Fugger, K., Povlsen, L. K., Beck, H., Sørensen, C. S., Petersen, N. H. T., Sorensen, P. H. B., Lukas, C., Bártek, J., et al. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2314 · Cited by 228
Replication-Dependent Radiosensitization of Human Glioma Cells by Inhibition of Poly(ADP-Ribose) Polymerase: Mechanisms and Therapeutic Potential
Dungey, F. A., Löser, D. A., & Chalmers, A. J. (2008) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2008.07.031 · Cited by 227
Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models
Ma, C. X., Cai, S., Li, S., Ryan, C. E., Guo, Z., Schaiff, W. T., Li, L., Hoog, J., Goiffon, R., Prat, A., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58765 · Cited by 227
The Meaning, Measurement and Modification of Hypoxia in the Laboratory and the Clinic
Hammond, E. M., Asselin, M., Forster, D. M., O’Connor, J. P. B., Senra, J. M., & Williams, K. J. (2014) · Clinical Oncology · doi:10.1016/j.clon.2014.02.002 · Cited by 227
Familial Pancreatic Cancer
Shi, C., Hruban, R. H., & Klein, A. P. (2009) · Archives of Pathology & Laboratory Medicine · doi:10.5858/133.3.365 · Cited by 227
Synthetic essentiality of chromatin remodelling factor CHD1 in PTEN-deficient cancer
Zhao, D., Lü, X., Wang, G., Lan, Z., Liao, W., Li, J., Liang, X., Chen, J., Shah, S. R., Shang, X., et al. (2017) · Nature · doi:10.1038/nature21357 · Cited by 227
Cancer Vulnerabilities Unveiled by Genomic Loss
Nijhawan, D., Zack, T. I., Ren, Y., Strickland, M. R., Lamothe, R. C., Schumacher, S. E., Tsherniak, A., Besche, H. C., Rosenbluh, J., Shehata, S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.07.023 · Cited by 225
Mechanisms of Therapy Resistance in Patient-Derived Xenograft Models of BRCA1-Deficient Breast Cancer
ter Brugge, P., Kristel, P., van der Burg, E., Boon, U., de Maaker, M., Lips, E. H., Mulder, L., de Ruiter, J., Moutinho, C., Gevensleben, H., et al. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw148 · Cited by 225
Endocrine Resistance in Hormone Receptor Positive Breast Cancer–From Mechanism to Therapy
Rani, A., Stebbing, J., Giamas, G., & Murphy, J. J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00245 · Cited by 224
The breast cancer susceptibility genes (BRCA) in breast and ovarian cancers
Paul, A. (2014) · Frontiers in bioscience · doi:10.2741/4230 · Cited by 224
The emerging role of DNA repair proteins as predictive, prognostic and therapeutic targets in cancer
Madhusudan, S., & Middleton, M. R. (2005) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2005.09.006 · Cited by 223
The ACF1 Complex Is Required for DNA Double-Strand Break Repair in Human Cells
Lan, L., Ui, A., Nakajima, S., Hatakeyama, K., Hoshi, M., Watanabe, R., Janicki, S. M., Ogiwara, H., Kohno, T., Kanno, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.12.003 · Cited by 221
Arginine Starvation Impairs Mitochondrial Respiratory Function in ASS1-Deficient Breast Cancer Cells
Qiu, F., Chen, Y.-R., Liu, X., Chu, C.-Y., Shen, L., Xu, J., Gaur, S., Forman, H. J., Zhang, H., Zheng, S. S., et al. (2014) · Science Signaling · doi:10.1126/scisignal.2004761 · Cited by 221
A Macrohistone Variant Links Dynamic Chromatin Compaction to BRCA1-Dependent Genome Maintenance
Khurana, S., Kruhlak, M. J., Kim, J., Tran, A. D., Liu, J., Nyswaner, K., Shi, L., Jailwala, P., Sung, M.-H., Hakim, O., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.024 · Cited by 220
A Third Zinc-binding Domain of Human Poly(ADP-ribose) Polymerase-1 Coordinates DNA-dependent Enzyme Activation
Langelier, M.-F., Servent, K. M., Rogers, E. E., & Pascal, J. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m708558200 · Cited by 220
PARP inhibitors in ovarian cancer
Franzese, E., Centonze, S., Diana, A., Carlino, F., Guerrera, L. P., Napoli, M. D., Vita, F. D., Pignata, S., Ciardiello, F., & Orditura, M. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.12.002 · Cited by 220
Rational Cancer Treatment Combinations: An Urgent Clinical Need
Boshuizen, J., & Peeper, D. S. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.05.031 · Cited by 221
Opportunities for the repurposing of PARP inhibitors for the therapy of non‐oncological diseases
Berger, N. A., Besson, V. C., Boulares, A. H., Bürkle, A., Chiarugi, A., Clark, R. S. B., Curtin, N. J., Cuzzocrea, S., Dawson, T. M., Dawson, V. L., et al. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13748 · Cited by 219
Self-citation
Poly(ADP-Ribose) polymerase (PARP) inhibitors: Exploiting a synthetic lethal strategy in the clinic
Yap, T. A., Sandhu, S. K., Carden, C. P., & Bono, J. S. D. (2011) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20095 · Cited by 218
RAD52 inactivation is synthetically lethal with deficiencies in BRCA1 and PALB2 in addition to BRCA2 through RAD51-mediated homologous recombination
Lok, B. H., Carley, A. C., Tchang, B., & Powell, S. N. (2012) · Oncogene · doi:10.1038/onc.2012.391 · Cited by 218
Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer
Petroni, G., Cantley, L. C., Santambrogio, L., Formenti, S. C., & Galluzzi, L. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00579-w · Cited by 224
Transcription–replication conflicts underlie sensitivity to PARP inhibitors
Petropoulos, M., Karamichali, A., Rossetti, G. G., Freudenmann, A., Iacovino, L. G., Dionellis, V. S., Sotiriou, S. K., & Halazonetis, T. D. (2024) · Nature · doi:10.1038/s41586-024-07217-2 · Cited by 217
PARP inhibitor combination therapy
Dréan, A., Lord, C. J., & Ashworth, A. (2016) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2016.10.010 · Cited by 216
Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities
Ge, T., Gu, X., Jia, R., Ge, S., Chai, P., Zhuang, A., & Fan, X. (2022) · 癌症：英文版 · doi:10.1002/cac2.12374 · Cited by 220
Basic Mechanisms of Therapeutic Resistance to Radiation and Chemotherapy in Lung Cancer
Willers, H., Azzoli, C. G., Santivasi, W. L., & Xia, F. (2013) · The Cancer Journal · doi:10.1097/ppo.0b013e318292e4e3 · Cited by 214
Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants
Pareja, F. G., Geyer, F. C., Marchiò, C., Burke, K. A., Weigelt, B., & Reis-Filho, J. S. (2016) · npj Breast Cancer · doi:10.1038/npjbcancer.2016.36 · Cited by 214
Failure of Iniparib to Inhibit Poly(ADP-Ribose) Polymerase In Vitro
Patel, A. G., Lorenzo, S. B. D., Flatten, K. S., Poirier, G. G., & Kaufmann, S. H. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2890 · Cited by 213
Fanconi anaemia genes and susceptibility to cancer
Mathew, C. G. (2006) · Oncogene · doi:10.1038/sj.onc.1209878 · Cited by 212
Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair
Bryant, H. E. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl108 · Cited by 212
Self-citation
DNA repair defects in cancer and therapeutic opportunitiesPreprint
Hopkins, J. L., Lan, L., & Zou, L. (2022) · Genes & Development · doi:10.1101/gad.349431.122 · Cited by 212
Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130
Hegan, D. C., Lü, Y., Stachelek, G. C., Crosby, M. E., Bindra, R. S., & Glazer, P. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904783107 · Cited by 211
Targeting DNA Repair Pathways for Cancer Treatment: what’s new?
Kelley, M. R., Logsdon, D. P., & Fishel, M. L. (2014) · Future Oncology · doi:10.2217/fon.14.60 · Cited by 211
Identifying chemogenetic interactions from CRISPR screens with drugZ
Colic, M., Wang, G., Zimmermann, M., Mascall, K. S., McLaughlin, M. E., Bertolet, L. L., Lenoir, W. F., Moffat, J., Angers, S., Durocher, D., et al. (2019) · Genome Medicine · doi:10.1186/s13073-019-0665-3 · Cited by 211
Therapeutic targets of triple‐negative breast cancer: a review
Jamdade, V., Sethi, N., Mundhe, N., Kumar, P., Lahkar, M., & Sinha, N. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13211 · Cited by 210
Targeting Androgen Receptor and DNA Repair in Metastatic Castration-Resistant Prostate Cancer: Results From NCI 9012
Hussain, M., Daignault‐Newton, S., Twardowski, P. W., Albany, C., Stein, M. N., Kunju, L. P., Siddiqui, J., Wu, Y.-M., Robinson, D. R., Lonigro, R. J., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.75.7310 · Cited by 210
Therapeutic targeting of tumor suppressor genes
Morris, L. G. T., & Chan, T. A.-T. (2014) · Cancer · doi:10.1002/cncr.29140 · Cited by 209
FANCD2 Maintains Fork Stability in BRCA1/2-Deficient Tumors and Promotes Alternative End-Joining DNA Repair
Kais, Z., Rondinelli, B., Holmes, A. L., O’Leary, C., Kozono, D., D’Andrea, A. D., & Ceccaldi, R. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.031 · Cited by 208
DNA damage response inhibitors in cancer therapy: lessons from the past, current status and future implications
Drew, Y., Zenke, F. T., & Curtin, N. J. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01060-w · Cited by 208
Self-citation
Synthetic lethality: exploiting the addiction of cancer to DNA repair
Shaheen, M. F., Allen, C., Nickoloff, J. A., & Hromas, R. (2011) · Blood · doi:10.1182/blood-2011-01-313734 · Cited by 207
Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress
Aggarwal, M., Sommers, J. A., Shoemaker, R. H., & Brosh, R. M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006423108 · Cited by 207
Hereditary Breast and Ovarian Cancer
Meindl, A., Ditsch, N. C., Kast, K., Rhiem, K., & Schmutzler, R. K. (2011) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.2011.0323 · Cited by 206
Does γH2AX foci formation depend on the presence of DNA double strand breaks?
Takahashi, A., & Ohnishi, T. (2005) · Cancer Letters · doi:10.1016/j.canlet.2005.07.016 · Cited by 205

Authors: Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T.
Affiliations: University of Sheffield (GB)
Stockholm University (SE)
Newcastle University (GB)
Corresponding author: Helleday, Thomas
ORCID: Bryant, Helen E.
Thomas, Huw D.
Curtin, Nicola J.
Helleday, Thomas
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2005-04-14
Volume: 434
Issue: 7035
Pages: 913-917
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature03443
OpenAlex: W2009007206
Cited by: 5,198
References: 26
Citations by year: 2026: 213 · 2025: 256 · 2024: 286 · 2023: 355 · 2022: 355 · 2021: 396 · 2020: 388 · 2019: 282 · 2018: 290 · 2017: 273 · 2016: 265 · 2015: 230 · 2014: 243 · 2013: 223 · 2012: 213
FWCI: 56.59
Type: journal article
Language: en
Update notices: erratum (2007-05-17)
Open access: green
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Newcastle University ePrints (Newcastle Univesity)
Funders: 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: PARP inhibitors, BRCA2 deficiency, homologous recombination, synthetic lethality, breast cancer, PARP1, DNA repair, replication fork collapse, single-strand breaks, γH2AX foci, RAD51 foci, base excision repair
MeSH terms: Poly(ADP-ribose) Polymerase Inhibitors, Animals, Antineoplastic Agents, Benzodiazepines, DNA Damage, DNA Repair, DNA Replication, Mice, Nude, Neoplasms, Poly(ADP-ribose) Polymerases, Xenograft Model Antitumor Assays, Genes, BRCA2, BRCA2 Protein, Cell Line, Tumor, Mice, Azulenes

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks