The DOI matches its Crossref record; 178 of the 180 references it cites were found in a registry or an index.
Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer
Open accessAbstract
Approximately 50% of epithelial ovarian cancers (EOC) exhibit defective DNA repair via homologous recombination (HR) due to genetic and epigenetic alterations of HR pathway genes. Defective HR is an important therapeutic target in EOC as exemplified by the efficacy of platinum analogues in this disease, as well as the advent of PARP inhibitors, which exhibit synthetic lethality when applied to HR-deficient cells. Here, we describe the genotypic and phenotypic characteristics of HR-deficient EOCs, discuss current and emerging approaches for targeting these tumors, and present challenges associated with these approaches, focusing on development and overcoming resistance. Significance: Defective DNA repair via HR is a pivotal vulnerability of EOC, particularly of the high-grade serous histologic subtype. Targeting defective HR offers the unique opportunity of exploiting molecular differences between tumor and normal cells, thereby inducing cancer-specific synthetic lethality; the promise and challenges of these approaches in ovarian cancer are discussed in this review. Cancer Discov; 5(11); 1137–54. ©2015 AACR.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The cited source says what the claim attributes to it.
In the citing paper
“Increasing evidence suggests that tumors with HR deficiency are more likely to be highly sensitive to platinum-based chemotherapy20–22.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Siegel, R. L., Miller, K. D., & Jemal, A. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21254 · Cited by 11,854
Siegel, R., Naishadham, D., & Jemal, A. (2013) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21166 · Cited by 11,825
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660
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
Specific 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
The resurgence of platinum-based cancer chemotherapy
Kèlland, L. R. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2167 · Cited by 4,733
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA 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
McGuire, W. P., Hoskins, W. J., Brady, M. F., Kucera, P. R., Partridge, E. E., Look, K. Y., Clarke‐Pearson, D. L., & Davidson, M. (1996) · New England Journal of Medicine · doi:10.1056/nejm199601043340101 · Cited by 2,798
Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer
Armstrong, D. K., Bundy, B. N., Wenzel, L. B., Huang, H. Q., Baergen, R. N., Lele, S., Copeland, L. J., Walker, J. L., & Burger, R. A. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052985 · Cited by 2,626
Audeh, M. W., Carmichael, J., Penson, R. T., Friedlander, M., Powell, B., Bell-McGuinn, K. M., Scott, C., Weitzel, J. N., Oaknin, A., Loman, N., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60893-8 · Cited by 2,279
Cited by
Sorted by citations
Items 901–946 of 946
Apport du séquençage d'exome pour le diagnostic et le traitement des maladies complexes
Jacob, A. (2020) · theses.fr (ABES) · doi:10.70675/867c4f59zac67z45c8z821ez3513ef63ba7c
Exploitation du défaut de réparation de l'ADN à l'aide de la stratégie d'inhibition de CDK
Orhan, E. (2022) · theses.fr (ABES) · doi:10.70675/40065dd4z1f5bz4361zaa67z59acc4e5d6c2
Serafini, M. (2024) · theses.fr (ABES) · doi:10.70675/ab8b1f5az3c15z4b5fzba28z247b40b8c7e0
Panjarwanto, D. A., Nabila, P., Octavia, L., Indrawan, I. W. A., Utomo, R. P., Permana, A. Y., Kaspan, Adnyana, I. G. H. E., Javier, R. M., & Akbar, M. Z. H. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1778168
LINE-1 transposon derived DNA lesions reshape the chromatin landscape to promote genome instabilityPreprint
Kumar, A., Parida, A. S., Bhatoa, K., Raghav, S. K., & Tiwari, B. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.20.719662
Lineage-specific lncRNAs critically determine cross-species differences in tumorsPreprint
Lin, J., Liu, X., & Zhu, H. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.01.722350
Caramelo, B., García-Berbel, P., Carmen, S. D., Terán, A. K. C., Corrêa, L., Martinez-Villaseñor, L., Sotelo, M., Rojo, F., Gómez‐Román, J., Durán, I., et al. (2026) · Cancers · doi:10.3390/cancers18101614
MTDH-SND1 disruption sensitizes ovarian cancer to ferroptosis and PARP inhibitionPreprint
Esmaeili, P., Nasimian, A., Ernestal, E., Persson, E., Bochis, B., Li, Y., Zamore, M., Gerdtsson, A. S., Kazi, J. U., & Levander, F. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.18.725896
Prakash, S., Mohanty, S. K., & Kumar, A. (2026) · In Silico Research in Biomedicine · doi:10.1016/j.insi.2026.100431
Kim, M., Seo, A. N., Park, J. Y., Yoon, G., & Park, J. Y. (2026) · Diagnostics · doi:10.3390/diagnostics16121802
Immunotherapy for gynecological tumors: From mechanism to clinical practice
Liu, J., Wu, M., & Wang, H. (2026) · Chinese Medical Journal · doi:10.1097/cm9.0000000000004166
Salko, M., Myllylahti, L., Palomino‐Echeverría, S., Tapper, J., Koivisto-Korander, R., Kanerva, A., Nelskylä, K., Loukovaara, M. J., Färkkilä, A., Haltia, U., et al. (2026) · International Journal of Gynecological Cancer · doi:10.1016/j.ijgc.2026.104818
Gertych, W., Trécourt, A., Faustine, M., Beacco, P., Brasselet, A., Carnet, M., Chevriaux, A., Chevrier, S., Morgane, D., Gibeaud, A., et al. (2026) · International Journal of Gynecological Cancer · doi:10.1016/j.ijgc.2026.104821
Colomar-Roig, M., Navarro, L., Megías, J., Abad, M. N., Roselló-Sastre, E., Santonja-López, N., & San‐Miguel, T. (2026) · Biomedicines · doi:10.3390/biomedicines14061405
Prognostic and predictive value of HRD in early triple negative breast cancer (TNBC)
Esposto, R., Marchi, L. D., Bonotto, M., Bortot, L., Poletto, E., Aprile, G., Cesselli, D., Puglisi, F., & Minisini, A. M. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105447
Takahashi, M., Ookubo, A., Yoshimura, T., Toyonaga, T., Saotome, K., Yoshihama, T., Jisaka, M., Sakamaki, T., Nakamura, K., Sakai, K., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-59944-3
Shah, N. A., Sarwar, M., & Ullah, E. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.25.734452
Roller, L., Zhou, N., Atre, I. D., Xiong, N., Li, J., Cheng, S.-C., Liu, N., Lacad, D., Adjei, M., Matulonis, U. A., et al. (2026) · Gynecologic Oncology · doi:10.1016/j.ygyno.2026.06.007
Self-citationModels of high-grade serous carcinoma of tubo-ovarian origin
Padmanabhan, A., Dwivedi, S. K. D., Merritt, M. A., Verma, P., Buckanovich, R. J., Lang, J. D., Dimmick, H. L., Nephew, K. P., Drapkin, R., Brubaker, L. W., et al. (2026) · Oncology Reviews · doi:10.3389/or.2026.1849834
Li, M., Xu, Y., Mai, Z., Ren, L., Yu, X., Chen, S. S., Ke, Z., & Yu, R. (2026) · CytoJournal · doi:10.25259/cytojournal_99_2025
Oliveira, A. F., Rosa, A. A. P. D. S., Tsunoda, A. T., Azevedo, B. R. B., Carvalho, E. M., Baiocchi, G., Lyra, J. S., Fernandes, P. H. D. S., Zanatto, R. M., Ribeiro, R., et al. (2026) · Journal of Surgical Oncology · doi:10.1002/jso.70302
Wang, J., Lu, Z., Ge, M., Zhang, X., Chen, D., & Peng, X. (2026) · Clinical Lung Cancer · doi:10.1016/j.cllc.2026.07.009
Edwards, C. C., Hedlich-Dwyer, J., Zhang, J., Zotto, V. L. D., Chen, D., Arend, R. C., & Gassman, N. R. (2026) · Cancers · doi:10.3390/cancers18152437
Harano, K., Nakao, T., Nishio, S., Katsuda, T., Tasaki, K., Takehara, K., Yokoyama, T., Furuya, H., Hongo, K., Asano, M., et al. (2026) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-25-4887
Molecular Characteristics and Carcinogenesis of Endometrial Cancer
Porcayo, M. A. T., & Guerrero, A. (2026) · Springer eBooks · doi:10.1007/978-3-032-13454-7_20
Anatomopathological Characteristics of Endometrial Carcinomas
Porcayo, M. A. T. (2026) · Springer eBooks · doi:10.1007/978-3-032-13454-7_23
Serafini, M., Fazio, F. D., Kieffer, Y., Djerroudi, L., Dec, L., Richard, M., Aubert, Y., Marchesoni-Acland, F., Díaz‐Muñoz, M. D., Vincent‐Salomon, A., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-76046-w
Self-citationFarrag, M. S., Masoud, R., Hemeda, M. S., Emarah, Z. A., Elnaghi, K., Abdelwahab, K., Farrag, N. S., Ibrahiem, A. T., Ehab, Z., Elrefaie, W. E., et al. (2026) · Journal of Molecular Histology · doi:10.1007/s10735-026-10944-7
Gordiichuk, P., Doronina, M., Ponomarova, O. V., Gordiichuk, M., Shapochka, D., Melnyk, D., & Tereshchenko, A. (2026) · Experimental Oncology · doi:10.15407/exp-oncology.2026.02.133
Predictive Biomarker Tests for Ovarian Cancer
Lawson, B. C., & Hagemann, I. S. (2026) · Surgical pathology clinics · doi:10.1016/j.path.2026.06.004
Myelonets define spatiotemporal immunosuppressive programs in ovarian cancerPreprint
Niemiec, I., Shabanova, A., Ruuska, E., Tissarinen, M., Liang, Z., Anandagoda, G., Shah, S., Kang, Z., Junquera, A., Salko, M., et al. (2026) · medRxiv · doi:10.64898/2026.08.26.26361128
McNevin, C. S., Murphy, K., Murchan, P., Hennessy, A., Fitzpatrick, O., O’Toole, S. A., Smyth, P. C., Atkinson, E., Thodi, G., Baird, A., et al. (2026) · European Journal of Human Genetics · doi:10.1038/s41431-026-02161-3
Vargas, E., Santiago‐Tovar, N., Murcia-Soriano, L. F., PatinoHerrera, A., Parra-Medina, R. S., & Riaño-Moreno, J. C. (2026) · AJOG Global Reports · doi:10.1016/j.xagr.2026.100693
Spatial transcriptomics reveals interferon pathway enrichment in early relapsing serous carcinomaPreprint
Niemeyer, F., Aho, N., Hänninen, S. M., Youssef, O., Carpén, O., Erickson, A. M., & Laury, A. R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.12.758400
Targeting the DNA Damage Response in Cancer
Qiao, Y., Kang, B., Zhang, J., Zhang, R., & Li, J. (2026) · MedComm · doi:10.1002/mco2.71020
Integrating Structural Genomic Features for Ovarian Cancer Risk Prediction in Diverse PopulationsPreprint
Fatapour, S., Villarreal-Calva, R. C., & Brody, J. P. (2026) · Research Square · doi:10.21203/rs.3.rs-11013359/v1
Pourcel, V., Drouin, Z., Létourneau, E., Gerber, Z., Malkoun, K.-R., Jean, D., Placet, M., & Labrie, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.29.755402
Walmsley, C. S., Rodriguez, A., Konstantinopoulos, P. A., Shapiro, G. I., Tolaney, S. M., Garber, J. E., & Lynce, F. C. (2026) · Journal of Clinical Investigation · doi:10.1172/jci207632
Self-citationIntegrating Molecular Biology into Surgical Strategy in Ovarian Cancer: Are We Ready?
González, E. R., Ángeles, M. A., Gauroy, É., Bataillon, G., & Martínez, A. (2026) · International Journal of Gynecological Cancer · doi:10.1016/j.ijgc.2026.105651
Cancer risks associated with BRCA1 and BRCA2 : Overview and management
Breen, K. E., Vashisth, S., & Liu, Y. L. (2026) · Cancer · doi:10.1002/cncr.70635
Viveros-Carreño, D. A., Mora‐Soto, N., Beshar, I., Agustí, N., Garcia, R., Rauh-Hain, A., & Pareja, R. (2026) · International Journal of Gynecological Cancer · doi:10.1016/j.ijgc.2026.105667
Liu, S., & Sun, C. (2026) · Cancer and Metastasis Reviews · doi:10.1007/s10555-026-10385-4
Simcock, B. J., Wilson, M. K., Vaughan, M. M., Sykes, P., Bell, R., Nevins, N., Mapagu, C., Bouantoun, N., Provan, P. J., Lee, E., et al. (2026) · New Zealand Medical Journal · doi:10.26635/6965.7288
BindingDB Entry 50016061: Topoisomerase I inhibitors: Challenges, progress and the road ahead.
BindingDB (2023) · UC San Diego · doi:10.7270/q25b06gc
Choi, Y. J., Lee, J., Nam, E. J., Kim, S. W., Kim, Y. T., & Lee, J. (2026) · Cancers · doi:10.3390/cancers18213508
Lim, S. O., Park, J., Lee, K., Kim, M., Lee, J., Lee, J.-W., Lee, D. W., Kang, H. J., & Lee, J. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01879-w
Metadata
- Authors
- Konstantinopoulos, P. A., Ceccaldi, R., Shapiro, G. I., & D'Andrea, A. D.
- Affiliations
- Harvard University (US)
- 2Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
- Corresponding author
- Konstantinopoulos, Panagiotis A.
- Venue
- Cancer Discovery
- Published
- 2015-11-01
- Volume
- 5
- Issue
- 11
- Pages
- 1137-1154
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC4631624
- OpenAlex
- W2179105349
- Cited by
- 945
- References
- 180
- Citations by year
- 2026: 67 · 2025: 97 · 2024: 109 · 2023: 126 · 2022: 115 · 2021: 102 · 2020: 100 · 2019: 74 · 2018: 74 · 2017: 54 · 2016: 27
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA090687, UM1CA186709, P50CA168504)
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Keywords
- homologous recombination deficiency, epithelial ovarian cancer, DNA repair deficiency, PARP inhibitors, synthetic lethality, platinum analogues, high-grade serous ovarian cancer, drug resistance, targeted therapy
- MeSH terms
- Carcinoma, Ovarian Epithelial, Animals, Antineoplastic Combined Chemotherapy Protocols, Clinical Trials as Topic, DNA Repair, Female, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Phenotype, Genetic Variation, Signal Transduction, Biomarkers, Gene Expression Regulation, Neoplastic, Treatment Outcome, Drug Resistance, Neoplasm, Molecular Targeted Therapy, Homologous Recombination
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
