DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer
Open accessAbstract
BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib. METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the prostate-specific antigen level or a confirmed reduction in the circulating tumor-cell count from 5 or more cells per 7.5 ml of blood to less than 5 cells per 7.5 ml. Targeted next-generation sequencing, exome and transcriptome analysis, and digital polymerase-chain-reaction testing were performed on samples from mandated tumor biopsies. RESULTS: Overall, 50 patients were enrolled; all had received prior treatment with docetaxel, 49 (98%) had received abiraterone or enzalutamide, and 29 (58%) had received cabazitaxel. Sixteen of 49 patients who could be evaluated had a response (33%; 95% confidence interval, 20 to 48), with 12 patients receiving the study treatment for more than 6 months. Next-generation sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes--including BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2--in 16 of 49 patients who could be evaluated (33%). Of these 16 patients, 14 (88%) had a response to olaparib, including all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations. The specificity of the biomarker suite was 94%. Anemia (in 10 of the 50 patients [20%]) and fatigue (in 6 [12%]) were the most common grade 3 or 4 adverse events, findings that are consistent with previous studies of olaparib. CONCLUSIONS: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. (Funded by Cancer Research UK and others; ClinicalTrials.gov number, NCT01682772; Cancer Research UK number, CRUK/11/029.).
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Accurate detection of HRD is of clinical relevance as it is indicative of sensitivity to targeted therapy with PARPi and DNA damaging reagents.
“Accurate detection of HRD is of clinical relevance as it is indicative of sensitivity to targeted therapy with poly ADP-ribose polymerase inhibitors (PARPi)3,4 as well as to DNA damaging reagents1.”
From Pan-cancer landscape of homologous recombination deficiency. (2020) · cites this paper as [4]
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New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534 · see citing works
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 · see citing works
Self-citationSpecific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005) · Nature · doi:10.1038/nature03443 · Cited by 5,198 · see citing works
Integrative Clinical Genomics of Advanced Prostate Cancer
Robinson, D., Van Allen, E. M., Wu, Y.-M., Schultz, N., Lonigro, R. J., Mosquera, J.-M., Montgomery, B., Taplin, M.-E., Pritchard, C. C., Attard, G., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.001 · Cited by 3,645 · see citing works
Self-citationInhibition of Poly(ADP-Ribose) Polymerase in Tumors from <i>BRCA</i> Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634 · see citing works
Self-citationDNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466 · see citing works
The mutational landscape of lethal castration-resistant prostate cancer
Grasso, C. S., Wu, Y.-M., Robinson, D. R., Cao, X., Dhanasekaran, S. M., Khan, A. P., Quist, M. J., Jing, X., Lonigro, R. J., Brenner, J. C., et al. (2012) · Nature · doi:10.1038/nature11125 · Cited by 2,517 · see citing works
Self-citationScher, H. I., Halabi, S., Tannock, I. F., Morris, M. J., Sternberg, C. N., Carducci, M. A., Eisenberger, M. A., Higano, C. S., Bubley, G. J., Dreicer, R., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.4487 · Cited by 2,228 · see citing works
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors
Murai, J., Huang, S.-Y. N., Das, B. B., Renaud, A., Zhang, Y., Doroshow, J. H., Ji, J. J., Takeda, S., & Pommier, Y. G. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-2753 · Cited by 2,217 · see citing works
Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53
Canman, C. E., Lim, D.-S., Cimprich, K. A., Taya, Y., Tamai, K., Sakaguchi, K., Appella, E., Kastan, M. B., & Siliciano, J. D. (1998) · Science · doi:10.1126/science.281.5383.1677 · Cited by 2,042 · see citing works
Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer
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. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1105535 · Cited by 1,891 · see citing works
Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation
Kaufman, B., Shapira‐Frommer, R., Schmutzler, R. K., Audeh, M. W., Friedlander, M. L., Balmañà, J., Mitchell, G., Fried, G., Stemmer, S. M., Hubert, A., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.56.2728 · Cited by 1,707 · see citing works
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. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70228-1 · Cited by 1,437 · see citing works
McCabe, N., Turner, N. C., Lord, C. J., Kluzek, K., Białkowska, A., Swift, S., Giavara, S., O’Connor, M. J., Tutt, A. N. J., Zdzienicka, M. Z., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0140 · Cited by 1,311 · see citing works
Self-citationPunctuated Evolution of Prostate Cancer Genomes
Baca, S. C., Prandi, D., Lawrence, M. S., Mosquera, J. M., Romanel, A., Drier, Y., Park, K., Kitabayashi, N., MacDonald, T. Y., Ghandi, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.021 · Cited by 1,300 · see citing works
Self-citationEarly Detection of Prostate Cancer: AUA Guideline
Carter, H. B., Albertsen, P. C., Barry, M. J., Etzioni, R., Freedland, S. J., Greene, K. L., Holmberg, L., Kantoff, P. W., Konety, B. R., Murad, M. H., et al. (2013) · The Journal of Urology · doi:10.1016/j.juro.2013.04.119 · Cited by 1,244 · see citing works
Fong, P. C. C., Yap, T. A., Boss, D. S., Carden, C. P., Mergui‐Roelvink, M., Gourley, C., Grève, J. D., Lubiński, J., Shanley, S., Messiou, C., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.9589 · Cited by 1,009 · see citing works
Self-citationCastro, E., Goh, C. L., Olmos, D., Saunders, E. J., Leongamornlert, D. A., Tymrakiewicz, M., Mahmud, N., Dadaev, T., Govindasami, K., Guy, M., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.1882 · Cited by 854 · see citing works
Self-citationHuman HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining
Miller, K. M., Tjeertes, J. V., Coates, J., Legube, G., Polo, S. E., Britton, S., & Jackson, S. P. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1899 · Cited by 629 · see citing works
Sandhu, S. K., Schelman, W. R., Wilding, G., Moreno, V., Baird, R. D., Miranda, S., Hylands, L., Riisnaes, R., Forster, M. D., Omlin, A. G., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70240-7 · Cited by 564 · see citing works
Self-citationBeltran, H., Yelensky, R., Frampton, G. M., Park, K., Downing, S. R., MacDonald, T. Y., Jarosz, M. V., Lipson, D., Tagawa, S. T., Nanus, D. M., et al. (2012) · European Urology · doi:10.1016/j.eururo.2012.08.053 · Cited by 450 · see citing works
Self-citationCollaborators, T. U., Kote‐Jarai, Z., Leongamornlert, D. A., Saunders, E. J., Tymrakiewicz, M., Castro, E., Mahmud, N., Guy, M., Edwards, S. E., O'Brien, L., et al. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.383 · Cited by 399 · see citing works
Self-citationThe Current State of Hormonal Therapy for Prostate Cancer
Hellerstedt, B. A., & Pienta, K. J. (2002) · CA: A Cancer Journal for Clinicians · doi:10.3322/canjclin.52.3.154 · Cited by 386 · see citing works
Scher, H. I., Heller, G., Molina, A., Attard, G., Danila, D. C., Jia, X., Peng, W., Sandhu, S. K., Olmos, D., Riisnaes, R., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.55.3487 · Cited by 380 · see citing works
Self-citationDominant Negative ATM Mutations in Breast Cancer Families
Chenevix‐Trench, G. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.3.205 · Cited by 376 · see citing works
Sternberg, C. N., Petrylak, D. P., Sartor, O. A., Witjes, J. A., Demkow, T., Ferrero, J.-., Eymard, J., Falcon, S. G., Calabrò, F., James, N. D., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.1228 · Cited by 340 · see citing works
Tumor clone dynamics in lethal prostate cancer
Carreira, S., Romanel, A., GOODALL, J. C., Grist, E., Ferraldeschi, R., Miranda, S., Prandi, D., Lorente, D., Frenel, J., Pezaro, C. J., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009448 · Cited by 337 · see citing works
Self-citationTranslating cancer research into targeted therapeutics
Bono, J. S. D., & Ashworth, A. (2010) · Nature · doi:10.1038/nature09339 · Cited by 333 · see citing works
Self-citationBuisson, R., Dion‐Côté, A., Coulombe, Y., Launay, H., Cai, H., Stasiak, A. Z., Stasiak, A., Xia, B., & Masson, J. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1915 · Cited by 303 · see citing works
Ferraldeschi, R., Nava Rodrigues, D., Riisnaes, R., Miranda, S., Figueiredo, I., Rescigno, P., Ravi, P., Pezaro, C., Omlin, A., Lorente, D., et al. (2015) · European Urology · doi:10.1016/j.eururo.2014.10.027 · Cited by 268 · see citing works
Self-citationHDAC 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 239 · see citing works
Fragments of ATM Which Have Dominant-Negative or Complementing Activity
Morgan, S. E., Lovly, C. M., Pandita, T. K., Shiloh, Y., & Kastan, M. B. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.4.2020 · Cited by 162 · see citing works
Morris, M. J., Molina, A., Small, E. J., Bono, J. S. D., Logothetis, C. J., Fizazi, K. S., SOUZA, P. D., Kantoff, P. W., Higano, C. S., Li, J., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.55.3875 · Cited by 133 · see citing works
Ceccaldi, R., O’Connor, K. W., Mouw, K. W., Li, A. Y., Matulonis, U. A., D’Andrea, A. D., & Konstantinopoulos, P. A. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2593 · Cited by 132 · see citing works
Barocas, D. A., Mallin, K., Graves, A. J., Penson, D. F., Palis, B. E., Winchester, D. P., & Chang, S. S. (2015) · The Journal of Urology · doi:10.1016/j.juro.2015.06.075 · Cited by 126 · see citing works
Barlow, C., Eckhaus, M., Schäffer, A. A., & Wynshaw-Boris, A. J. (1999) · Nature Genetics · doi:10.1038/7684 · Cited by 123 · see citing works
Turenne, G. A., Paul, P., Laflair, L., & Price, B. D. (2001) · Oncogene · doi:10.1038/sj.onc.1204665 · Cited by 120 · see citing works
Beamish, H., Kedar, P. S., Kaneko, H., Chen, P., Fukao, T., Peng, C., Beresten, S., Gueven, N., Purdie, D. M., Lees‐Miller, S. P., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203801200 · Cited by 119 · see citing works
Predictive biomarkers for cancer therapy with PARP inhibitors
Michels, J., Vitale, I., Saparbaev, M. K., Castedo, M., & Kroemer, G. (2013) · Oncogene · doi:10.1038/onc.2013.352 · Cited by 113 · see citing works
Histone Deacetylase Regulation of ATM-Mediated DNA Damage Signaling
Thurn, K. T., Thomas, S., Raha, P., Qureshi, I., & Münster, P. N. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-1242 · Cited by 108 · see citing works
Synergistic Loss of Prostate Cancer Cell Viability by Coinhibition of HDAC and PARP
Chao, O. S., & Goodman, O. B. (2014) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-14-0173 · Cited by 93 · see citing works
Sandhu, S. K., Omlin, A. G., Hylands, L., Miranda, S., Barber, L. J., Riisnaes, R., Reid, A. H. M., Attard, G., Chen, L., Kozarewa, I., et al. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt074 · Cited by 69 · see citing works
Self-citationOng, M., Carreira, S., GOODALL, J. C., Mateo, J., Figueiredo, I., Rodrigues, D. N., Perkins, G., Seed, G., Yap, T. A., Attard, G., et al. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.350 · Cited by 39 · see citing works
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A comprehensive map of molecular drug targets
Santos, R., Ursu, O., Gaulton, A., Bento, A. P., Donadi, R. S., Bologa, C. G., Karlsson, A., Al-Lazikani, B., Hersey, A., Oprea, T. I., et al. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.230 · Cited by 2,427 · see citing works
Olaparib for Metastatic Castration-Resistant Prostate Cancer
de Bono, J., Mateo, J., Fizazi, K., Saad, F., Shore, N., Sandhu, S., Chi, K. N., Sartor, O., Agarwal, N., Olmos, D., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1911440 · Cited by 2,323 · see citing works
Self-citationThe multifaceted roles of PARP1 in DNA repair and chromatin remodelling
Ray Chaudhuri, A., & Nussenzweig, A. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.53 · Cited by 1,786 · see citing works
Genomic correlates of clinical outcome in advanced prostate cancer
Abida, W., Cyrta, J., Heller, G., Prandi, D., Armenia, J., Coleman, I., Cieslik, M., Benelli, M., Robinson, D., Van Allen, E. M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902651116 · Cited by 1,372 · see citing works
Self-citationLord, C. J., & Ashworth, A. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.21 · Cited by 1,257 · see citing works
Self-citationState-of-the-art strategies for targeting the DNA damage response in cancer
Pilié, P. G., Tang, C., Mills, G. B., & Yap, T. A. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0114-z · Cited by 1,189 · see citing works
Swisher, E. M., Lin, K. K., Oza, A. M., Scott, C. L., Giordano, H., Sun, J., Konecny, G. E., Coleman, R. L., Tinker, A. V., O'Malley, D. M., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30559-9 · Cited by 1,196 · see citing works
HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
Davies, H., Glodzik, D., Morganella, S., Yates, L. R., Staaf, J., Zou, X., Ramakrishna, M., Martin, S., Boyault, S., Sieuwerts, A. M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4292 · Cited by 1,086 · see citing works
Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Parker, C., Castro, E., Fizazi, K., Heidenreich, A., Ost, P., Procopio, G., Tombal, B., & Gillessen, S. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.06.011 · Cited by 977 · see citing works
Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
Study, T. P., Schumacher, F. R., (APCB), A. P. C. B., Study, T. I., Canary PASS Investigators, Breast and Prostate Cancer Cohort Consortium (BPC3), The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, (CAPS), C. O. T. P. I. S., Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci (PEGASUS), The Genetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium, et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0142-8 · Cited by 902 · see citing works
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Quigley, D. A., Dang, H. X., Zhao, S. G., Lloyd, P., Aggarwal, R., Alumkal, J. J., Foye, A., Kothari, V., Perry, M. D., Bailey, A. M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.039 · Cited by 733 · see citing works
Self-citationPascual, J., Attard, G., Bidard, F.-C., Curigliano, G., De Mattos-Arruda, L., Diehn, M., Italiano, A., Lindberg, J., Merker, J. D., Montagut, C., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.05.520 · Cited by 783 · see citing works
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Gupte, R., Liu, Z., & Kraus, W. L. (2017) · Genes & Development · doi:10.1101/gad.291518.116 · Cited by 681 · see citing works
Fang, E. F., Kassahun, H., Croteau, D. L., Scheibye-Knudsen, M., Marosi, K., Lu, H., Shamanna, R. A., Kalyanasundaram, S., Bollineni, R. C., Wilson, M. A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.004 · Cited by 575 · see citing works
Sartor, O., & de Bono, J. S. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1701695 · Cited by 546 · see citing works
Self-citationPan-cancer landscape of homologous recombination deficiency.
Nguyen, L., W. M. Martens, J., Van Hoeck, A., & Cuppen, E. (2020) · Nature communications · doi:10.1038/s41467-020-19406-4 · Cited by 532 · see citing works
“Accurate detection of HR deficiency (HRD) is of clinical relevance as it is indicative of sensitivity to targeted therapy with poly ADP-ribose polymerase inhibitors (PARPi)[3, 4] as well as to DNA damaging reagents[1].”
BackgroundNuhn, P., De Bono, J. S., Fizazi, K., Freedland, S. J., Grilli, M., Kantoff, P. W., Sonpavde, G., Sternberg, C. N., Yegnasubramanian, S., & Antonarakis, E. S. (2019) · European Urology · doi:10.1016/j.eururo.2018.03.028 · Cited by 437 · see citing works
Self-citationProstate-specific Membrane Antigen Heterogeneity and DNA Repair Defects in Prostate Cancer
Paschalis, A., Sheehan, B., Riisnaes, R., Rodrigues, D. N., Gurel, B., Bertan, C., Ferreira, A., Lambros, M. B. K., Seed, G., Yuan, W., et al. (2019) · European Urology · doi:10.1016/j.eururo.2019.06.030 · Cited by 455 · see citing works
Self-citationViswanathan, S. R., Ha, G., Hoff, A. M., Wala, J. A., Carrot-Zhang, J., Whelan, C. W., Haradhvala, N. J., Freeman, S. S., Reed, S. C., Rhoades, J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.036 · Cited by 365 · see citing works
Biomarkers for Homologous Recombination Deficiency in Cancer
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Development of PARP and immune-checkpoint inhibitor combinations
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Yurgelun, M. B., Chittenden, A. B., Morales-Oyarvide, V., Rubinson, D. A., Dunne, R. F., Kozak, M. M., Qian, Z. R., Welch, M. W., Brais, L. K., Da Silva, A., et al. (2019) · Genetics in Medicine · doi:10.1038/s41436-018-0009-5 · Cited by 217 · see citing works
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Li, X., Baek, G., Ramanand, S. G., Sharp, A., Gao, Y., Yuan, W., Welti, J., Rodrigues, D. N., Dolling, D., Figueiredo, I., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.078 · Cited by 148 · see citing works
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Weigelt, B., Bi, R., Kumar, R., Blecua, P., Mandelker, D. L., Geyer, F. C., Pareja, F., James, P. A., kConFab Investigators, Couch, F. J., et al. (2018) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djy028 · Cited by 128 · see citing works
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Arena, S., Corti, G., Durinikova, E., Montone, M., Reilly, N. M., Russo, M., Lorenzato, A., Arcella, P., Lazzari, L., Rospo, G., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2409 · Cited by 115 · see citing works
Stelloo, S., Nevedomskaya, E., Kim, Y., Hoekman, L., Bleijerveld, O. B., Mirza, T., Wessels, L. F. A., van Weerden, W. M., Altelaar, A. F. M., Bergman, A. M., et al. (2018) · Oncogene · doi:10.1038/onc.2017.330 · Cited by 118 · see citing works
HER3 Is an Actionable Target in Advanced Prostate Cancer
Gil, V., Miranda, S., Riisnaes, R., Gurel, B., D’Ambrosio, M., Vasciaveo, A., Crespo, M., Ferreira, A., Brina, D., Troiani, M., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-3360 · Cited by 68 · see citing works
Self-citationRuiz de Porras, V., Font, A., & Aytes, A. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.08.033 · Cited by 65 · see citing works
Understanding Resistance Mechanisms and Expanding the Therapeutic Utility of PARP Inhibitors
Lim, J., & Tan, D. S. P. (2017) · Cancers · doi:10.3390/cancers9080109 · Cited by 52 · see citing works
Toward a More Precise Future for Oncology
Murciano-Goroff, Y. R., Taylor, B. S., Hyman, D. M., & Schram, A. M. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.03.014 · Cited by 48 · see citing works
Targeting the DNA Damage Response Pathway as a Novel Therapeutic Strategy in Colorectal Cancer
Catalano, F., Borea, R., Puglisi, S., Boutros, A., Gandini, A., Cremante, M., Martelli, V., Sciallero, S., & Puccini, A. (2022) · Cancers · doi:10.3390/cancers14061388 · Cited by 44 · see citing works
Pancreas cancer and <i>BRCA</i> : A critical subset of patients with improving therapeutic outcomes
Momtaz, P., O’Connor, C. A., Chou, J. F., Capanu, M., Park, W., Bandlamudi, C., Berger, M. F., Kelsen, D. P., Suehnholz, S. P., Chakravarty, D., et al. (2021) · Cancer · doi:10.1002/cncr.33812 · Cited by 44 · see citing works
Targeting DNA Damage Response and Immune Checkpoint for Anticancer Therapy
Huang, J.-L., Chang, Y.-T., Hong, Z.-Y., & Lin, C.-S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063238 · Cited by 42 · see citing works
Comprehensive analysis of DNA damage repair deficiency in 10,284 pan–cancer study
Xiao, Y., Lu, D., Lei, M., Xie, W., Chen, Y., Zheng, Y., Wang, C., Zhao, J., Zhu, Z., Zhao, X., et al. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-5449 · Cited by 22 · see citing works
Maurice Dror, C., Chi, K. N., & Khalaf, D. J. (2021) · Translational Andrology and Urology · doi:10.21037/tau-20-1341 · Cited by 14 · see citing works
- Authors
- Mateo, J., Carreira, S., Sandhu, S., Miranda, S., Mossop, H., Perez-Lopez, R., Nava Rodrigues, D., Robinson, D., Omlin, A., Tunariu, N., Boysen, G., Porta, N., Flohr, P., Gillman, A., Figueiredo, I., Paulding, C., Seed, G., Jain, S., Ralph, C., Protheroe, A., Hussain, S., Jones, R., Elliott, T., McGovern, U., Bianchini, D., Goodall, J., Zafeiriou, Z., Williamson, C. T., Ferraldeschi, R., Riisnaes, R., Ebbs, B., Fowler, G., Roda, D., Yuan, W., Wu, Y.-M., Cao, X., Brough, R., Pemberton, H., A’Hern, R., Swain, A., Kunju, L. P., Eeles, R., Attard, G., Lord, C. J., Ashworth, A., Rubin, M. A., Knudsen, K. E., Feng, F. Y., Chinnaiyan, A. M., Hall, E., & de Bono, J. S.
- Affiliations
- Institute of Cancer Research (GB)
- Royal Marsden NHS Foundation Trust (GB)
- University of Michigan (US)
- Queen's University Belfast (GB)
- University of Leeds (GB)
- Churchill Hospital (GB)
- University of Liverpool (GB)
- Beatson West of Scotland Cancer Centre (GB)
- The Christie Hospital (GB)
- University College Hospital (GB)
- Weill Cornell Medicine (US)
- Thomas Jefferson University (US)
- ORCID
- Carreira, Suzanne
- Sandhu, Shahneen
- Miranda, Susana
- Mossop, Helen
- Robinson, Dan
- Omlin, Aurelius
- Tunariu, Nina
- Boysen, Gunther
- Flohr, Penny
- Figueiredo, Ines
- Seed, George
- Jain, Suneil
- Ralph, Christy
- Protheroe, Andrew
- Hussain, Syed
- Jones, Robert
- Elliott, Tony
- McGovern, Ursula
- Bianchini, Diletta
- Goodall, Jane
- Zafeiriou, Zafeiris
- Riisnaes, Ruth
- Roda, Desamparados
- Yuan, Wei
- Wu, Yi-Mi
- Cao, Xuhong
- Brough, Rachel
- A’Hern, Roger
- Swain, Amanda
- Kunju, Lakshmi P.
- Eeles, Rosalind
- Attard, Gerhardt
- Lord, Christopher J.
- Ashworth, Alan
- Rubin, Mark A.
- Knudsen, Karen E.
- Feng, Felix Y.
- Chinnaiyan, Arul M.
- Hall, Emma
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-10-29
- Volume
- 373
- Issue
- 18
- Pages
- 1697-1708
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5228595
- OpenAlex
- W2235405584
- Cited by
- 2,185
- References
- 43
- Citations by year
- 2026: 85 · 2025: 114 · 2024: 140 · 2023: 180 · 2022: 199 · 2021: 236 · 2020: 284 · 2019: 248 · 2018: 257 · 2017: 242 · 2016: 182 · 2015: 10 · 2014: 3
- FWCI
- 100.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- New England Journal of Medicine (publishedVersion, other-oa)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, other-oa)
- The Medicine Forum (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- American Association for Cancer Research
- Prostate Cancer Foundation
- Bristol-Myers Squibb
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Celgene
- Royal Marsden NHS Foundation Trust
- Les Laboratories Pierre Fabre
- Cancer Research UK (14276, C12540/A13230, C12540 A12829, C1491/ A15955, 12829, C1491/A9895, 15007, 13239, A15955, 13230, 17528, CRUK/11/029, A9895)
- National Institute for Health and Care Research (NF-SI-0510-10096, CL-2008-22-001)
- Prostate Cancer UK (PG12-49)
- European Commission (625792)
- Public Health Agency (SPI/3315/06)
- Oncolytics Biotech
- Astellas Pharma
- European Society for Medical Oncology
- Genentech
- Stand Up To Cancer
- Medical Research Council (MR/M003272/1)
- National Cancer Institute (R01CA182569, P30CA056036)
- Cilag
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Keywords
- olaparib, PARP inhibition, metastatic castration-resistant prostate cancer, DNA repair deficiency, Fanconi anemia genes, CHEK2, germline mutations, somatic deletions, biomarker-guided therapy, targeted next-generation sequencing, circulating tumor cells, prostate-specific antigen, anemia, fatigue, treatment response rate
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Adult, Aged, Anemia, Antineoplastic Agents, DNA Repair, Enzyme Inhibitors, Fatigue, Humans, Male, Middle Aged, Mutation, Neoplasm Metastasis, Phthalazines, Piperazines, Prostatic Neoplasms, Genes, Tumor Suppressor, Drug Resistance, Neoplasm, Genes, BRCA2, Ataxia Telangiectasia Mutated Proteins
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