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

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

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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

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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.

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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

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Review of Poly (ADP-ribose) Polymerase (PARP) Mechanisms of Action and Rationale for Targeting in Cancer and Other Diseases
Morales, J. C., Li, L.-S., Fattah, F. J., Dong, Y., Bey, E. A., Patel, M., Gao, J., & Boothman, D. A. (2013) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukaryotgeneexpr.2013006875 · Cited by 629
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/s43586-021-00093-4 · Cited by 626
PARP is activated at stalled forks to mediate Mre11‐dependent replication restart and recombination
Bryant, H. E., Petermann, E., Schultz, N., Jemth, A., Loseva, O., Issaeva, N., Johansson, F., Fernandez, S., McGlynn, P., & Helleday, T. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.206 · Cited by 623
Self-citation
The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance
Bouwman, P., & Jonkers, J. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3342 · Cited by 615
4-[3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: A Novel Bioavailable Inhibitor of Poly(ADP-ribose) Polymerase-1
Menear, K. A., Adcock, C., Boulter, R., Cockcroft, X. F., Copsey, L., Cranston, A. N., Dillon, K. J., Drzewiecki, J., Garman, S., Gomez, S., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm8001263 · Cited by 608
PARPi Triggers the STING-Dependent Immune Response and Enhances the Therapeutic Efficacy of Immune Checkpoint Blockade Independent of BRCAness
Shen, J., Zhao, W., Ju, Z., Wang, L., Peng, Y., Labrie, M., Yap, T. A., Mills, G. B., & Peng, G. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-1003 · Cited by 614
BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution
Deng, C. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl010 · Cited by 604
Regulation of DNA Damage Responses by Ubiquitin and SUMO
Jackson, S. P., & Durocher, D. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.017 · Cited by 601
The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases
Paul, O. H. (2007) · Frontiers in bioscience · doi:10.2741/2909 · Cited by 601
How the Fanconi Anemia Pathway Guards the Genome
Moldovan, G., & D’Andrea, A. D. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102108-134222 · Cited by 601
The role of double-strand break repair — insights from human genetics
O’Driscoll, M., & Jeggo, P. A. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1746 · Cited by 600
Parthanatos: mitochondrial‐linked mechanisms and therapeutic opportunities
Fatokun, A. A., Dawson, V. L., & Dawson, T. M. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12416 · Cited by 594
Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study
Liu, J. F., Barry, W. T., Birrer, M. J., Lee, J.-M., Buckanovich, R. J., Fleming, G. F., Rimel, B. J., Buss, M. K., Nattam, S. R., Hurteau, J. A., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70391-2 · Cited by 592
The DNA Damage Response: Implications for Tumor Responses to Radiation and Chemotherapy
Goldstein, M., & Kastan, M. B. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-081313-121208 · Cited by 590
Poly(ADP-ribose) polymerase inhibition: past, present and future
Curtin, N. J., & Szabó, C. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0076-6 · Cited by 595
Self-citation
PARP inhibitor resistance: the underlying mechanisms and clinical implications
Li, H., Liu, Z., Wu, N., Chen, Y., Cheng, Q., & Wang, J. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01227-0 · Cited by 578
PARP inhibition elicits STING-dependent antitumor immunity in brca1-deficient ovarian cancer
Ding, L., Kim, H.-J., Wang, Q., Kearns, M., Jiang, T., Ohlson, C. E., Li, B. B., Xie, S., Liu, J. F., Stover, E. H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.054 · Cited by 572
Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells
Patel, A. G., Sarkaria, J. N., & Kaufmann, S. H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013715108 · Cited by 568
Enabling personalized cancer medicine through analysis of gene-expression patterns
Veer, L. V. ‘., & Bernards, R. (2008) · Nature · doi:10.1038/nature06915 · Cited by 558
Triple‑negative breast cancer therapy: Current and future perspectives (Review)
Won, K., & Spruck, C. (2020) · International Journal of Oncology · doi:10.3892/ijo.2020.5135 · Cited by 555
Understanding and overcoming resistance to PARP inhibitors in cancer therapy
Dias, M. P., Moser, S. C., Ganesan, S., & Jonkers, J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00532-x · Cited by 544
Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial
Agarwal, N., Azad, A. A., Carles, J., Fay, A. P., Matsubara, N., Heinrich, D., Szczylik, C., De Giorgi, U., Young Joung, J., Fong, P. C. C., et al. (2023) · The Lancet · doi:10.1016/s0140-6736(23)01055-3 · Cited by 538
Loss of 53BP1 Causes PARP Inhibitor Resistance in Brca1 -Mutated Mouse Mammary Tumors
Jaspers, J. E., Kersbergen, A. J., Boon, U., Sol, W., van Deemter, L., Zander, S. A. L., Drost, R., Wientjens, E., Ji, J. J., Aly, A., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0049 · Cited by 532
Topoisomerase I poisoning results in PARP-mediated replication fork reversal
Chaudhuri, A. R., Hashimoto, Y., Herrador, R., Neelsen, K. J., Fachinetti, D., Bermejo, R., Cocito, A., Costanzo, V., & Lopes, M. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2258 · Cited by 524
Chemotherapeutic Approaches for Targeting Cell Death Pathways
Ricci, M., & Zong, W. (2006) · The Oncologist · doi:10.1634/theoncologist.11-4-342 · Cited by 523
ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors
Shen, J., Peng, Y., Wei, L., Zhang, W., Yang, L., Lan, L., Kapoor, P., Ju, Z., Mo, Q., Shih, I.-M., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0849 · Cited by 522
The diverse roles and clinical relevance of PARPs in DNA damage repair: Current state of the art
Vos, M. D., Schreiber, V., & Dantzer, F. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.03.018 · Cited by 522
Acetylation limits 53BP1 association with damaged chromatin to promote homologous recombination
Tang, J., Cho, N. W., Cui, G., Manion, E. M., Shanbhag, N. M., Botuyan, M. V., Mer, G., & Greenberg, R. A. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2499 · Cited by 521
DNA damage signalling guards against activated oncogenes and tumour progression
Bartek, J., Bartkova, J., & Lukas, J. (2007) · Oncogene · doi:10.1038/sj.onc.1210881 · Cited by 521
MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
Gad, H., Koolmeister, T., Jemth, A., Eshtad, S., Jacques, S. A., Ström, C. E., Svensson, L. M., Schultz, N., Lundbäck, T., Einarsdottir, B. O., et al. (2014) · Nature · doi:10.1038/nature13181 · Cited by 520
Self-citation
High speed of fork progression induces DNA replication stress and genomic instability
Maya-Mendoza, A., Moudry, P., Merchut-Maya, J. M., Lee, M., Strauss, R., & Bartek, J. (2018) · Nature · doi:10.1038/s41586-018-0261-5 · Cited by 514
Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors
Flynn, R. L., Cox, K. E., Jeitany, M., Wakimoto, H., Bryll, A. R., Ganem, N. J., Bersani, F., Pineda, J. R., Suvà, M. L., Benes, C. H., et al. (2015) · Science · doi:10.1126/science.1257216 · Cited by 515
ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer
Miller, R. E., Leary, A. F., Scott, C. L., Serra, V., Lord, C. J., Bowtell, D. D. L., Chang, D. K.-F., Garsed, D. W., Jonkers, J., Ledermann, J. A., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.08.2102 · Cited by 507
Rational combinations of targeted cancer therapies: background, advances and challenges
Jin, H., Wang, L., & Bernards, R. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00615-z · Cited by 503
Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing
Walsh, T., Lee, M. K., Casadei, S., Thornton, A., Stray, S. M., Pennil, C. C., Nord, A. S., Mandell, J. B., Swisher, E. M., & King, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007983107 · Cited by 503
Mechanisms of PARP inhibitor sensitivity and resistance
D’Andrea, A. D. (2018) · DNA repair · doi:10.1016/j.dnarep.2018.08.021 · Cited by 502
Beyond chemotherapy: targeted therapies in ovarian cancer
Yap, T. A., Carden, C. P., & Kaye, S. B. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2583 · Cited by 501
Ubiquitin ligases in oncogenic transformation and cancer therapy
Senft, D., Qi, J., & Ronai, Z. A. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.105 · Cited by 499
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Singleton, D. C., Macann, A., & Wilson, W. R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00539-4 · Cited by 507
Synthetic Lethality and Cancer Therapy: Lessons Learned from the Development of PARP Inhibitors
Lord, C. J., Tutt, A. N. J., & Ashworth, A. (2014) · Annual Review of Medicine · doi:10.1146/annurev-med-050913-022545 · Cited by 493
Unravelling the biology of SCLC: implications for therapy
Sabari, J. K., Lok, B. H., Laird, J. H., Poirier, J. T., & Rudin, C. M. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.71 · Cited by 493
Methylating Agents and DNA Repair Responses: Methylated Bases and Sources of Strand Breaks
Wyatt, M. D., & Pittman, D. L. (2006) · Chemical Research in Toxicology · doi:10.1021/tx060164e · Cited by 487
BMN 673, a Novel and Highly Potent PARP1/2 Inhibitor for the Treatment of Human Cancers with DNA Repair Deficiency
Shen, Y., Rehman, F. L., Feng, Y., Boshuizen, J., Bajrami, I., Elliott, R. J. R., Wang, B., Lord, C. J., Post, L. E., & Ashworth, A. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1391 · Cited by 486
Synthetic lethality as an engine for cancer drug target discovery
Huang, A., Garraway, L. A., Ashworth, A., & Weber, B. L. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0046-z · Cited by 490
DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity
Gupta, R., Somyajit, K., Narita, T., Maskey, E., Stanlie, A., Kremer, M., Typas, D., Lammers, M., Mailand, N., Nussenzweig, A., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.050 · Cited by 480
Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors
Wahlberg, E., Karlberg, T., Kouznetsova, E., Markova, N., Macchiarulo, A., Thorsell, A. G., Pol, E., Frostell, Å., Ekblad, T., Öncü, D., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2121 · Cited by 479
Phase II, Open-Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of Olaparib, a Poly (ADP-Ribose) Polymerase Inhibitor, and Pegylated Liposomal Doxorubicin in Patients With BRCA1 or BRCA2 Mutations and Recurrent Ovarian Cancer
Kaye, S. B., Lubiński, J., Matulonis, U. A., Ang, J. E., Gourley, C., Karlan, B. Y., Amit, A., Bell‐McGuinn, K. M., Chen, L.-M., Friedlander, M. L., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.36.9215 · Cited by 478
Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1 -mutated basal-like breast cancer
Liu, X., Holstege, H. H., van der Gulden, H. M. L., Treur-Mulder, M., Zevenhoven, J., Velds, A., Kerkhoven, R. M., van Vliet, M. H., Wessels, L. F. A., Peterse, J. L., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702969104 · Cited by 476
Strategies for optimizing the response of cancer and normal tissues to radiation
Moding, E. J., Kastan, M. B., & Kirsch, D. G. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4003 · Cited by 474
Dissecting the Heterogeneity of Triple-Negative Breast Cancer
Metzger, O., Tutt, A. N. J., de Azambuja, E., Saini, K. S., Viale, G., Loi, S., Bradbury, I., Bliss, J. M., Azim, H. A., Ellis, P., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.38.2010 · Cited by 471
The Fanconi Anemia/BRCA pathway: new faces in the crowdPreprint
Kennedy, R. D., & D’Andrea, A. D. (2005) · Genes & Development · doi:10.1101/gad.1370505 · Cited by 471
PARP Inhibitor Resistance: A Tug-of-War in BRCA-Mutated Cells
Noordermeer, S. M., & van Attikum, H. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.07.008 · Cited by 472
Mechanisms of resistance to therapies targeting BRCA-mutant cancers
Lord, C. J., & Ashworth, A. (2013) · Nature Medicine · doi:10.1038/nm.3369 · Cited by 467
A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations
Toledo, L. I., Murga, M., Zur, R., Soria, R., Rodriguez, A., Martinez, S., Oyarzabal, J., Pastor, J., Bischoff, J. R., & Fernandez-Capetillo, O. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2076 · Cited by 465
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance
Pettitt, S. J., Krastev, D. B., Brandsma, I., Dréan, A., Song, F., Aleksandrov, R., Harrell, M. I., Menon, M. R., Brough, R., Campbell, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03917-2 · Cited by 463
Biology of Poly(ADP-Ribose) Polymerases: The Factotums of Cell Maintenance
Bai, P. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.01.034 · Cited by 457
Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial
Ledermann, J. A., Harter, P., Gourley, C., Friedlander, M. L., Vergote, I. B., Rustin, G. J. S., Scott, C. L., Meier, W., Shapira‐Frommer, R., Safra, T., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30376-x · Cited by 455
RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer
Cruz, C., Castroviejo‐Bermejo, M., Gutiérrez‐Enríquez, S., Llop‐Guevara, A., Ibrahim, Y. H., Gris‐Oliver, A., Bonache, S., Morancho, B., Bruna, A., Rueda, O. M., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy099 · Cited by 454
The Landscape of Targeted Therapies in TNBC
Vagia, E., Mahalingam, D., & Cristofanilli, M. (2020) · Cancers · doi:10.3390/cancers12040916 · Cited by 453
Rucaparib or Physician’s Choice in Metastatic Prostate Cancer
Fizazi, K., Piulats, J. M., Reaume, M. N., Ostler, P., McDermott, R., Gingerich, J. R., Pintus, E., Sridhar, S. S., Bambury, R. M., Emmenegger, U., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2214676 · Cited by 449
BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
Lin, K., Harrell, M. I., Oza, A. M., Oaknin, A., Ray-Coquard, I. L., Tinker, A. V., Helman, E., Radke, M. R., Say, C., Vo, L.-T., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0715 · Cited by 449
Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers
Golan, T., Kanji, Z. S., Epelbaum, R., Devaud, N., Dagan, E., Holter, S., Aderka, D., Paluch–Shimon, S., Kaufman, B., Gershoni‐Baruch, R., et al. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.418 · Cited by 442
miR-182-Mediated Downregulation of BRCA1 Impacts DNA Repair and Sensitivity to PARP Inhibitors
Moskwa, P., Buffa, F. M., Pan, Y., Panchakshari, R. A., Gottipati, P., Muschel, R. J., Beech, J. S., Kulshrestha, R., Abdelmohsen, K., Weinstock, D. M., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.12.005 · Cited by 436
Self-citation
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Ashworth, A., & Lord, C. J. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0055-6 · Cited by 434
Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells
Dev, H., Chiang, T.-W. W., Lescale, C., de Krijger, I., Martin, A. G., Pilger, D., Coates, J., Sczaniecka-Clift, M., Wei, W., Ostermaier, M., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0140-1 · Cited by 433
Recent Advances in the Treatment of Breast Cancer
Tong, C. W. S., Wu, M., Cho, W. C. S., & To, K. K. W. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00227 · Cited by 428
Mechanistic Rationale for Inhibition of Poly(ADP-Ribose) Polymerase in ETS Gene Fusion-Positive Prostate Cancer
Brenner, J. C., Ateeq, B., Li, Y., Yocum, A. K., Cao, Q., Asangani, I. A., Patel, S., Wang, X., Liang, H., Yu, J., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.04.010 · Cited by 424
RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis
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O'Reilly, E. M., Lee, J. W., Zalupski, M. M., Capanu, M., Park, J., Golan, T., Tahover, E., Lowery, M. A., Chou, J. F., Sahai, V., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.02931 · Cited by 420
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Cortesi, L., Rugo, H. S., & Jackisch, C. (2021) · Targeted Oncology · doi:10.1007/s11523-021-00796-4 · Cited by 411
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Alhmoud, J. F., Woolley, J. F., Moustafa, A. A., & Malki, M. I. (2020) · Cancers · doi:10.3390/cancers12041050 · Cited by 410
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BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ
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Molecular pathogenesis of Fanconi anemia: recent progress
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Retracted

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

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

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