{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:13:48Z","timestamp":1770819228668,"version":"3.50.1"},"reference-count":174,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T00:00:00Z","timestamp":1625788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/QUI\/50006\/2020"],"award-info":[{"award-number":["UID\/QUI\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Precision medicine aims to identify specific molecular alterations, such as driver mutations, allowing tailored and effective anticancer therapies. Poly(ADP)-ribose polymerase inhibitors (PARPi) are the prototypical example of targeted therapy, exploiting the inability of cancer cells to repair DNA damage. Following the concept of synthetic lethality, PARPi have gained great relevance, particularly in BRCA1 dysfunctional cancer cells. In fact, BRCA1 mutations culminate in DNA repair defects that can render cancer cells more vulnerable to therapy. However, the efficacy of these drugs has been greatly affected by the occurrence of resistance due to multi-connected DNA repair pathways that may compensate for each other. Hence, the search for additional effective agents targeting DNA damage repair (DDR) is of crucial importance. In this context, BRCA1 has assumed a central role in developing drugs aimed at inhibiting DNA repair activity. Collectively, this review provides an in-depth understanding of the biology and regulatory mechanisms of DDR pathways, highlighting the potential of DDR-associated molecules, particularly BRCA1 and its interconnected partners, in precision cancer medicine. It also affords an overview about what we have achieved and a reflection on how much remains to be done in this field, further addressing encouraging clues for the advance of DDR targeted therapy.<\/jats:p>","DOI":"10.3390\/cancers13143438","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T04:14:57Z","timestamp":1625804097000},"page":"3438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Exploiting DNA Damage Repair in Precision Cancer Therapy: BRCA1 as a Prime Therapeutic Target"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-2601","authenticated-orcid":false,"given":"Liliana","family":"Raimundo","sequence":"first","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5895-6951","authenticated-orcid":false,"given":"Juliana","family":"Calheiros","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-4939","authenticated-orcid":false,"given":"Luc\u00edlia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394424","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e000285","DOI":"10.1136\/esmoopen-2017-000285","article-title":"Global cancer control: Responding to the growing burden, rising costs and inequalities in access","volume":"3","author":"Prager","year":"2018","journal-title":"ESMO Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"255cm10","DOI":"10.1126\/scitranslmed.3009148","article-title":"Genomic Complexity: A Call to Action","volume":"6","author":"Hait","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6472","DOI":"10.1038\/sj.onc.1206955","article-title":"Genetic and epigenetic alterations as hallmarks of the intricate road to cancer","volume":"22","author":"Macaluso","year":"2003","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.molcel.2015.10.040","article-title":"Targeting the DNA Damage Response in Cancer","volume":"60","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.critrevonc.2018.10.012","article-title":"Targeting homologous repair deficiency in breast and ovarian cancers: Biological pathways, preclinical and clinical data","volume":"133","author":"Chartron","year":"2019","journal-title":"Crit. Rev. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1200\/EDBK_238473","article-title":"The DNA Damaging Revolution: PARP Inhibitors and Beyond","volume":"39","author":"Yap","year":"2019","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1158\/2159-8290.CD-16-0860","article-title":"Targeting DNA Repair in Cancer: Beyond PARP Inhibitors","volume":"7","author":"Brown","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"879","DOI":"10.3389\/fcell.2020.564601","article-title":"PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance","volume":"8","author":"Rose","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_10","first-page":"165","article-title":"Genomic Instability and Cancer","volume":"5","author":"Yao","year":"2014","journal-title":"J. Carcinog. Mutagenesis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"417","DOI":"10.2174\/187152008784220294","article-title":"DNA Repair Proteins as Molecular Targets for Cancer Therapeutics","volume":"8","author":"Kelley","year":"2008","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_12","first-page":"6221","article-title":"BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis","volume":"63","author":"Quinn","year":"2003","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17079","DOI":"10.1073\/pnas.0806092105","article-title":"High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs","volume":"105","author":"Rottenberg","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1093\/jnci\/djh312","article-title":"The Role of BRCA1 in the Cellular Response to Chemotherapy","volume":"96","author":"Kennedy","year":"2004","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1158\/1078-0432.CCR-13-2287","article-title":"Germline and Somatic Mutations in Homologous Recombination Genes Predict Platinum Response and Survival in Ovarian, Fallopian Tube, and Peritoneal Carcinomas","volume":"20","author":"Pennington","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1038\/onc.2013.329","article-title":"Opportunities and hurdles in the treatment of BRCA1-related breast cancer","volume":"33","author":"Drost","year":"2013","journal-title":"Oncogene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1016\/j.cub.2012.07.034","article-title":"A DNA-Damage Selective Role for BRCA1 E3 Ligase in Claspin Ubiquitylation, CHK1 Activation, and DNA Repair","volume":"22","author":"Sato","year":"2012","journal-title":"Curr. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.ccr.2011.11.014","article-title":"BRCA1 RING Function Is Essential for Tumor Suppression but Dispensable for Therapy Resistance","volume":"20","author":"Drost","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_19","first-page":"83","article-title":"Haploinsufficient tumor suppressor genes","volume":"118","author":"Inoue","year":"2017","journal-title":"Adv. Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.chembiol.2017.08.027","article-title":"Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy","volume":"24","author":"Hengel","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nrc3342","article-title":"The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance","volume":"12","author":"Bouwman","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.pharmthera.2014.12.001","article-title":"ATM and ATR as therapeutic targets in cancer","volume":"149","author":"Weber","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1016\/j.febslet.2010.07.029","article-title":"The MRN complex in double-strand break repair and telomere maintenance","volume":"584","author":"Lamarche","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_24","first-page":"13837","article-title":"Targeting DNA double-strand break signalling and repair: Recent advances in cancer therapy","volume":"143","author":"Bolck","year":"2013","journal-title":"Swiss Med. Wkly."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nrc.2015.21","article-title":"BRCAness revisited","volume":"16","author":"Lord","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1126\/science.2270482","article-title":"Linkage of early-onset familial breast cancer to chromosome 17q","volume":"250","author":"Hall","year":"1990","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.1128\/MCB.01646-13","article-title":"BRCA1 Pathway Function in Basal-Like Breast Cancer Cells","volume":"34","author":"Hill","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.7150\/jca.30410","article-title":"BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance","volume":"10","author":"Gorodetska","year":"2019","journal-title":"J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7380","DOI":"10.1128\/MCB.01075-08","article-title":"Rapid Recruitment of BRCA1 to DNA Double-Strand Breaks Is Dependent on Its Association with Ku80","volume":"28","author":"Wei","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2902","DOI":"10.4161\/cc.7.18.6679","article-title":"DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells","volume":"7","author":"Mao","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1042\/BST20120140","article-title":"BRCA1 exon 11 alternative splicing, multiple functions and the association with cancer","volume":"40","author":"Tammaro","year":"2012","journal-title":"Biochem. Soc. Trans."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nrc3181","article-title":"BRCA1 and BRCA2: Different roles in a common pathway of genome protection","volume":"12","author":"Roy","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e201204005","DOI":"10.5936\/csbj.201204005","article-title":"Structure-Function of the Tumor Suppressor BRCA","volume":"1","author":"Clark","year":"2012","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17724","DOI":"10.1074\/jbc.R115.667931","article-title":"Deciphering the BRCA1 Tumor Suppressor Network","volume":"290","author":"Jiang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4161\/rna.28458","article-title":"BRCA1 exon 11 a model of long exon splicing regulation","volume":"11","author":"Raponi","year":"2014","journal-title":"RNA Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biocel.2015.12.008","article-title":"New concepts on BARD1: Regulator of BRCA pathways and beyond","volume":"72","author":"Ratajska","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6755","DOI":"10.1093\/emboj\/cdf691","article-title":"Activation of the E3 ligase function of the BRCA1\/BARD1 complex by polyubiquitin chains","volume":"21","author":"Mallery","year":"2002","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1158\/0008-5472.CAN-05-3296","article-title":"BRCA1 DNA-Binding Activity Is Stimulated by BARD1","volume":"66","author":"Simons","year":"2006","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"22085","DOI":"10.1074\/jbc.M201252200","article-title":"Autoubiquitination of the BRCA1\u00b7BARD1 RING Ubiquitin Ligase","volume":"277","author":"Chen","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4100","DOI":"10.1158\/0008-5472.CAN-05-4430","article-title":"Identification of Domains of BRCA1 Critical for the Ubiquitin-Dependent Inhibition of Centrosome Function","volume":"66","author":"Sankaran","year":"2006","journal-title":"Cancer Res."},{"key":"ref_41","first-page":"833","article-title":"Structure of a BRCA1-BARD1 heterodimeric RING-RING complex","volume":"8","author":"Brzovic","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21315","DOI":"10.1074\/jbc.M200769200","article-title":"BARD1 Induces BRCA1 Intranuclear Foci Formation by Increasing RING-dependent BRCA1 Nuclear Import and Inhibiting BRCA1 Nuclear Export","volume":"277","author":"Fabbro","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3509","DOI":"10.1038\/sj.onc.1207427","article-title":"Nuclear\u2013cytoplasmic translocation of BARD1 is linked to its apoptotic activity","volume":"23","author":"Jefford","year":"2004","journal-title":"Oncogene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.yexcr.2003.09.027","article-title":"Cytoplasmic mislocalization of BRCA1 caused by cancer-associated mutations in the BRCT domain","volume":"293","author":"Rodriguez","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/s41418-018-0153-0","article-title":"Regulating BRCA1 protein stability by cathepsin S-mediated ubiquitin degradation","volume":"26","author":"Kim","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1667\/RR1290.1","article-title":"Impact of RING and BRCT Domain Mutations on BRCA1 Protein Stability, Localization and Recruitment to DNA Damage","volume":"174","author":"Nelson","year":"2010","journal-title":"Radiat. Res."},{"key":"ref_47","first-page":"360","article-title":"BRCA1\u2013BARD1 promotes RAD51-mediated homologous DNA pairing","volume":"550","author":"Zhao","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Cimmino, F., Formicola, D., and Capasso, M. (2017). Dualistic Role of BARD1 in Cancer. Genes, 8.","DOI":"10.3390\/genes8120375"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"31251","DOI":"10.1074\/jbc.M405372200","article-title":"BRCA1-BARD1 Complexes Are Required for p53Ser-15 Phosphorylation and a G1\/S Arrest following Ionizing Radiation-induced DNA Damage","volume":"279","author":"Fabbro","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6152","DOI":"10.1038\/sj.onc.1203974","article-title":"BRCA1 and cell signaling","volume":"19","author":"Wang","year":"2000","journal-title":"Oncogene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1111\/febs.13150","article-title":"BRCA1, a \u2018complex\u2019 protein involved in the maintenance of genomic stability","volume":"282","author":"Savage","year":"2015","journal-title":"FEBS J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7730","DOI":"10.1038\/sj.onc.1205971","article-title":"Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells","volume":"21","author":"Kawai","year":"2002","journal-title":"Oncogene"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5854","DOI":"10.1038\/sj.onc.1209872","article-title":"The role of BRCA1 in transcriptional regulation and cell cycle control","volume":"25","author":"Mullan","year":"2006","journal-title":"Oncogene"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10555-012-9403-7","article-title":"Mouse models of BRCA1 and their application to breast cancer research","volume":"32","author":"Dine","year":"2013","journal-title":"Cancer Metastasis Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.1111\/j.1742-4658.2010.07735.x","article-title":"BRCA1 16 years later: Risk-associated BRCA1 mutations and their functional implications","volume":"277","author":"Linger","year":"2010","journal-title":"FEBS J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/nrm2831","article-title":"BRCA1 and its toolbox for the maintenance of genome integrity","volume":"11","author":"Huen","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s10147-017-1182-2","article-title":"BRCA1 gene: Function and deficiency","volume":"23","author":"Takaoka","year":"2017","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.currproblcancer.2018.01.001","article-title":"BRCA1 mutation spectrum, functions, and therapeutic strategies: The story so far","volume":"42","author":"Sharma","year":"2018","journal-title":"Curr. Probl. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/cr.2008.1","article-title":"Homologous recombination in DNA repair and DNA damage tolerance","volume":"18","author":"Li","year":"2008","journal-title":"Cell Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev-biochem-013118-111058","article-title":"The BRCA Tumor Suppressor Network in Chromosome Damage Repair by Homologous Recombination","volume":"88","author":"Zhao","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Situ, Y., Chung, L., Lee, C.S., and Ho, V. (2019). MRN (MRE11-RAD50-NBS1) Complex in Human Cancer and Prognostic Implications in Colorectal Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040816"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1093\/nar\/gkw1241","article-title":"And-1 is required for homologous recombination repair by regulating DNA end resection","volume":"45","author":"Li","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1517\/14728222.2010.525221","article-title":"Cyclin-dependent kinases (cdks) and the DNA damage response: Rationale for cdk inhibitor\u2013chemotherapy combinations as an anticancer strategy for solid tumors","volume":"14","author":"Johnson","year":"2010","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1083\/jcb.201302145","article-title":"The interaction between CtIP and BRCA1 is not essential for resection-mediated DNA repair or tumor suppression","volume":"201","author":"Reczek","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1084\/jem.20131939","article-title":"CtIP-mediated resection is essential for viability and can operate independently of BRCA1","volume":"211","author":"Polato","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev.biochem.77.061306.125255","article-title":"Mechanism of Eukaryotic Homologous Recombination","volume":"77","author":"Filippo","year":"2008","journal-title":"Annu. Rev. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5351","DOI":"10.1038\/s41467-018-07798-3","article-title":"Kinase-dead ATR differs from ATR loss by limiting the dynamic exchange of ATR and RPA","volume":"9","author":"Menolfi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7155","DOI":"10.1073\/pnas.0811159106","article-title":"PALB2 is an integral component of the BRCA complex required for homologous recombination repair","volume":"106","author":"Sy","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.cub.2009.02.018","article-title":"PALB2 Links BRCA1 and BRCA2 in the DNA-Damage Response","volume":"19","author":"Zhang","year":"2009","journal-title":"Curr. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"a016600","DOI":"10.1101\/cshperspect.a016600","article-title":"Homologous Recombination and Human Health: The Roles of BRCA1, BRCA2, and Associated Proteins","volume":"7","author":"Prakash","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"859","DOI":"10.4161\/cc.7.7.5613","article-title":"Break-induced replication: What is it and what is it for?","volume":"7","author":"Llorente","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_72","first-page":"188339","article-title":"BRCA1\/P53: Two strengths in cancer chemoprevention","volume":"1873","author":"Raimundo","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA) Bioenerg."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kotsopoulos, J., Huzarski, T., Gronwald, J., Singer, C.F., Moller, P., Lynch, H.T., Armel, S., Karlan, B., Foulkes, W.D., and Neuhausen, S.L. (2017). Bilateral Oophorectomy and Breast Cancer Risk inBRCA1andBRCA2Mutation Carriers. J. Natl. Cancer Inst., 109.","DOI":"10.1093\/jnci\/djw177"},{"key":"ref_74","unstructured":"National Human Genome Research Institute (2020, March 18). Breast Cancer Information Core (BIC) Database, Available online: http:\/\/research.nhgri.nih.gov\/bic\/."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3322\/caac.21560","article-title":"The current state of molecular testing in the treatment of patients with solid tumors","volume":"69","author":"Goldberg","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1158\/0008-5472.CAN-16-2025","article-title":"Out-RANKing BRCA1 in Mutation Carriers","volume":"77","author":"Nolan","year":"2017","journal-title":"Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1172\/JCI70196","article-title":"BRCA1185delAG tumors may acquire therapy resistance through expression of RING-less BRCA1","volume":"126","author":"Drost","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/humu.20590","article-title":"Does the nonsense-mediated mRNA decay mechanism prevent the synthesis of truncated BRCA1, CHK2, and p53 proteins?","volume":"29","author":"Anczukow","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1200\/JCO.2004.04.188","article-title":"Bilateral Prophylactic Mastectomy Reduces Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group","volume":"22","author":"Rebbeck","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1016\/j.celrep.2016.10.077","article-title":"CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer","volume":"17","author":"Johnson","year":"2016","journal-title":"Cell Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nrclinonc.2016.66","article-title":"Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease","volume":"13","author":"Bianchini","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3233\/BD-2010-0306","article-title":"BRCA1\/2 mutations and triple negative breast cancers","volume":"32","author":"Peshkin","year":"2011","journal-title":"Breast Dis."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Shimizu, Y., Luk, H., Horio, D., Miron, P., Griswold, M., Iglehart, D., Hernandez, B., Killeen, J., and ElShamy, W.M. (2012). BRCA1-IRIS Overexpression Promotes Formation of Aggressive Breast Cancers. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034102"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e000357","DOI":"10.1136\/esmoopen-2018-000357","article-title":"How shall we treat early triple-negative breast cancer (TNBC): From the current standard to upcoming immuno-molecular strategies","volume":"3","author":"Park","year":"2018","journal-title":"ESMO Open"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1093\/jnci\/djt095","article-title":"Cancer Risks for BRCA1 and BRCA2 Mutation Carriers: Results From Prospective Analysis of EMBRACE","volume":"105","author":"Mavaddat","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13048-019-0484-6","article-title":"Current strategies for the targeted treatment of high-grade serous epithelial ovarian cancer and relevance of BRCA mutational status","volume":"12","author":"Gadducci","year":"2019","journal-title":"J. Ovarian Res."},{"key":"ref_87","first-page":"1","article-title":"Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes","volume":"10","author":"Peron","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e879","DOI":"10.1002\/mgg3.879","article-title":"The role of BRCA1\/2 in hereditary and familial breast and ovarian cancers","volume":"7","author":"Hawsawi","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"8109","DOI":"10.1158\/0008-5472.CAN-06-0140","article-title":"Deficiency in the Repair of DNA Damage by Homologous Recombination and Sensitivity to Poly(ADP-Ribose) Polymerase Inhibition","volume":"66","author":"McCabe","year":"2006","journal-title":"Cancer Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nrc1691","article-title":"The concept of synthetic lethality in the context of anticancer therapy","volume":"5","author":"Kaelin","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nature03443","article-title":"Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase","volume":"434","author":"Bryant","year":"2005","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1158\/1078-0432.CCR-12-0163","article-title":"Molecular Pathways: Targeting PARP in Cancer Treatment","volume":"19","author":"Do","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"198","DOI":"10.7150\/ijbs.17240","article-title":"Reverse the Resistance to PARP Inhibitors","volume":"13","author":"Kim","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1042\/bj1850775","article-title":"Novel inhibitors of poly(ADP-ribose) synthetase","volume":"185","author":"Purnell","year":"1980","journal-title":"Biochem. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/2346585","article-title":"Predictors and Modulators of Synthetic Lethality: An Update on PARP Inhibitors and Personalized Medicine","volume":"2016","author":"Murata","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Keung, M.Y.T., Wu, Y., and Vadgama, J.V. (2019). PARP Inhibitors as a Therapeutic Agent for Homologous Recombination Deficiency in Breast Cancers. J. Clin. Med., 8.","DOI":"10.3390\/jcm8040435"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5177","DOI":"10.2147\/OTT.S184971","article-title":"Evidence to date: Talazoparib in the treatment of breast cancer","volume":"12","author":"Exman","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.2147\/OTT.S69935","article-title":"Profile of veliparib and its potential in the treatment of solid tumors","volume":"8","author":"Wagner","year":"2015","journal-title":"OncoTargets Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/PPO.0b013e3181d78223","article-title":"Poly(ADP-Ribose) Polymerase Inhibitors","volume":"16","author":"Gartner","year":"2010","journal-title":"Cancer J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/S1470-2045(19)30396-1","article-title":"Pamiparib in combination with tislelizumab in patients with advanced solid tumours: Results from the dose-escalation stage of a multicentre, open-label, phase 1a\/b trial","volume":"20","author":"Friedlander","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"41307","DOI":"10.18632\/oncotarget.5846","article-title":"E7449: A dual inhibitor of PARP1\/2 and tankyrase1\/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling","volume":"6","author":"Mcgonigle","year":"2015","journal-title":"Oncotarget"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6875","DOI":"10.1021\/acs.jmedchem.5b00680","article-title":"Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy","volume":"58","author":"Papeo","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.dnarep.2011.07.006","article-title":"The PARP inhibitor PJ34 causes a PARP1-independent, p21 dependent mitotic arrest","volume":"10","author":"Madison","year":"2011","journal-title":"DNA Repair"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1158\/1940-6207.CAPR-14-0047","article-title":"The PARP Inhibitors, Veliparib and Olaparib, Are Effective Chemopreventive Agents for Delaying Mammary Tumor Development in BRCA1-deficient Mice","volume":"7","author":"To","year":"2014","journal-title":"Cancer Prev. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/S1470-2045(17)30469-2","article-title":"Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1\/2 mutation (SOLO2\/ENGOT-Ov21): A double-blind, randomised, placebo-controlled, phase 3 trial","volume":"18","author":"Ledermann","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"7170","DOI":"10.1021\/jm901188v","article-title":"Discovery of 2-{4-[(3S)-Piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): A Novel Oral Poly(ADP-ribose)polymerase (PARP) Inhibitor Efficacious in BRCA-1 and -2 Mutant Tumors","volume":"52","author":"Jones","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/j.chembiol.2016.10.011","article-title":"Proteome-wide Profiling of Clinical PARP Inhibitors Reveals Compound-Specific Secondary Targets","volume":"23","author":"Knezevic","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41571-018-0114-z","article-title":"State-of-the-art strategies for targeting the DNA damage response in cancer","volume":"16","author":"Tang","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1021\/acs.jmedchem.7b01896","article-title":"The Identification of Potent, Selective, and Orally Available Inhibitors of Ataxia Telangiectasia Mutated (ATM) Kinase: The Discovery of AZD0156 (8-{6-[3-(Dimethylamino)propoxy]pyridin-3-yl}-3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one)","volume":"61","author":"Pike","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"eaat1719","DOI":"10.1126\/sciadv.aat1719","article-title":"The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models","volume":"4","author":"Durant","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1158\/1535-7163.MCT-09-0519","article-title":"Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion","volume":"8","author":"Golding","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Yang, F., Qian, X.-J., Qin, W., Deng, R., Wu, X.-Q., Qin, J., Feng, G.-K., and Zhu, X.-F. (2013). Dual Phosphoinositide 3-Kinase\/Mammalian Target of Rapamycin Inhibitor NVP-BEZ235 Has a Therapeutic Potential and Sensitizes Cisplatin in Nasopharyngeal Carcinoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059879"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/aps.2013.22","article-title":"NVP-BEZ235, a novel dual PI3K\/mTOR inhibitor, enhances the radiosensitivity of human glioma stem cells in vitro","volume":"34","author":"Wang","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.toxlet.2013.04.021","article-title":"Dual inhibitor of phosphoinositide 3-kinase\/mammalian target of rapamycin NVP-BEZ235 effectively inhibits cisplatin-resistant urothelial cancer cell growth through autophagic flux","volume":"220","author":"Li","year":"2013","journal-title":"Toxicol. Lett."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"107518","DOI":"10.1016\/j.pharmthera.2020.107518","article-title":"Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy","volume":"210","author":"Gorecki","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e441","DOI":"10.1038\/cddis.2012.181","article-title":"Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation","volume":"3","author":"Fokas","year":"2012","journal-title":"Cell Death Dis."},{"key":"ref_117","first-page":"791","article-title":"Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor","volume":"2","author":"Bunch","year":"1996","journal-title":"Clin. Cancer Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1158\/1078-0432.CCR-16-1782","article-title":"Phase I Study of GDC-0425, a Checkpoint Kinase 1 Inhibitor, in Combination with Gemcitabine in Patients with Refractory Solid Tumors","volume":"23","author":"Infante","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.radonc.2017.09.043","article-title":"ATR\/CHK1 inhibitors and cancer therapy","volume":"126","author":"Qiu","year":"2018","journal-title":"Radiother. Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1158\/1535-7163.MCT-08-0492","article-title":"AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies","volume":"7","author":"Zabludoff","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1158\/1535-7163.MCT-06-0371","article-title":"Cell cycle phenotype-based optimization of G2-abrogating peptides yields CBP501 with a unique mechanism of action at the G2 checkpoint","volume":"6","author":"Sha","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1080\/13543784.2018.1511700","article-title":"Strategic development of AZD1775, a Wee1 kinase inhibitor, for cancer therapy","volume":"27","author":"Fu","year":"2018","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1158\/1078-0432.CCR-17-3421","article-title":"A First-in-Human Phase 1 Study of LY3023414, an Oral PI3K\/mTOR Dual Inhibitor, in Patients with Advanced Cancer","volume":"24","author":"Bendell","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"5599","DOI":"10.1021\/acs.jmedchem.5b00627","article-title":"Optimization of a Series of Triazole Containing Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors and the Discovery of CC-115","volume":"58","author":"Mortensen","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1182\/blood-2016-02-700328","article-title":"Dual TORK\/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia","volume":"128","author":"Thijssen","year":"2016","journal-title":"Blood"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"74688","DOI":"10.18632\/oncotarget.20342","article-title":"CC-115, a dual inhibitor of mTOR kinase and DNA-PK, blocks DNA damage repair pathways and selectively inhibits ATM-deficient cell growth in vitro","volume":"8","author":"Tsuji","year":"2017","journal-title":"Oncotarget"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/cmdc.201700143","article-title":"Targeting DNA-Dependent Protein Kinase for Cancer Therapy","volume":"12","author":"Harnor","year":"2017","journal-title":"ChemMedChem"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"25833","DOI":"10.18632\/oncotarget.25383","article-title":"VX-984 is a selective inhibitor of non-homologous end joining, with possible preferential activity in transformed cells","volume":"9","author":"Khan","year":"2018","journal-title":"Oncotarget"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-12836-9","article-title":"AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity","volume":"10","author":"Fok","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.neo.2019.06.006","article-title":"AsiDNA Treatment Induces Cumulative Antitumor Efficacy with a Low Probability of Acquired Resistance","volume":"21","author":"Jdey","year":"2019","journal-title":"Neoplasia"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.3389\/fonc.2019.01388","article-title":"Harnessing DNA Double-Strand Break Repair for Cancer Treatment","volume":"9","author":"Trenner","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/s41571-018-0055-6","article-title":"Synthetic lethal therapies for cancer: What\u2019s next after PARP inhibitors?","volume":"15","author":"Ashworth","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"9152","DOI":"10.1158\/0008-5472.CAN-04-2727","article-title":"Identification and Characterization of a Novel and Specific Inhibitor of the Ataxia-Telangiectasia Mutated Kinase ATM","volume":"64","author":"Hickson","year":"2004","journal-title":"Cancer Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"7466","DOI":"10.1158\/0008-5472.CAN-08-0763","article-title":"Transient Inhibition of ATM Kinase Is Sufficient to Enhance Cellular Sensitivity to Ionizing Radiation","volume":"68","author":"Rainey","year":"2008","journal-title":"Cancer Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1158\/1535-7163.MCT-17-0975","article-title":"Orally Bioavailable and Blood\u2013Brain Barrier-Penetrating ATM Inhibitor (AZ32) Radiosensitizes Intracranial Gliomas in Mice","volume":"17","author":"Karlin","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"107391","DOI":"10.1016\/j.pharmthera.2019.07.002","article-title":"ATM in DNA repair in cancer","volume":"203","author":"Jin","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"5678","DOI":"10.1093\/nar\/gkp593","article-title":"Inhibition of ATR protein kinase activity by schisandrin B in DNA damage response","volume":"37","author":"Nishida","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/bjc.2011.243","article-title":"Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines","volume":"105","author":"Peasland","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1021\/jm101520v","article-title":"Discovery of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a Potent, Selective, and Orally Available Mammalian Target of Rapamycin (mTOR) Inhibitor for Treatment of Cancer","volume":"54","author":"Liu","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nsmb.2076","article-title":"A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations","volume":"18","author":"Toledo","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nchembio.573","article-title":"Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR","volume":"7","author":"Reaper","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_142","first-page":"2419","article-title":"Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase","volume":"54","author":"Powis","year":"1994","journal-title":"Cancer Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1016\/S0021-9258(17)37680-9","article-title":"A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)","volume":"269","author":"Vlahos","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"111692","DOI":"10.1016\/j.mrfmmm.2020.111692","article-title":"Targeting DNA-PK in cancer","volume":"821","author":"Damia","year":"2020","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1021\/jm049526a","article-title":"Selective Benzopyranone and Pyrimido [2,1-a] isoquinolin-4-one Inhibitors of DNA-Dependent Protein Kinase: Synthesis, Structure\u2212Activity Studies, and Radiosensitization of a Human Tumor Cell Line in Vitro","volume":"48","author":"Griffin","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"6083","DOI":"10.1016\/j.bmcl.2004.09.060","article-title":"Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries","volume":"14","author":"Leahy","year":"2004","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1158\/1535-7163.MCT-11-0535","article-title":"Chemosensitization of Cancer Cells by KU-0060648, a Dual Inhibitor of DNA-PK and PI-3K","volume":"11","author":"Munck","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1172\/JCI127483","article-title":"Selective DNA-PKcs inhibition extends the therapeutic index of localized radiotherapy and chemotherapy","volume":"130","author":"Willoughby","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"5354","DOI":"10.1158\/0008-5472.CAN-05-4275","article-title":"Preclinical Evaluation of a Potent Novel DNA-Dependent Protein Kinase Inhibitor NU7441","volume":"66","author":"Zhao","year":"2006","journal-title":"Cancer Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1158\/1535-7163.MCT-15-0996","article-title":"Characterization of LY3023414, a Novel PI3K\/mTOR Dual Inhibitor Eliciting Transient Target Modulation to Impede Tumor Growth","volume":"15","author":"Smith","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Prakash, A., Garcia-Moreno, J.F., Brown, J.A.L., and Bourke, E. (2018). Clinically Applicable Inhibitors Impacting Genome Stability. Molecules, 23.","DOI":"10.3390\/molecules23051166"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Nogueira, A., Fernandes, M., Catarino, R., and Medeiros, R. (2019). RAD52 Functions in Homologous Recombination and Its Importance on Genomic Integrity Maintenance and Cancer Therapy. Cancers, 11.","DOI":"10.3390\/cancers11111622"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1093\/nar\/gkp200","article-title":"DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange","volume":"37","author":"Ishida","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1021\/cb100428c","article-title":"Identification of Specific Inhibitors of Human RAD51 Recombinase Using High-Throughput Screening","volume":"6","author":"Huang","year":"2011","journal-title":"ACS Chem. Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"7347","DOI":"10.1093\/nar\/gks353","article-title":"RI-1: A chemical inhibitor of RAD51 that disrupts homologous recombination in human cells","volume":"40","author":"Budke","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1021\/jm301565b","article-title":"An Optimized RAD51 Inhibitor That Disrupts Homologous Recombination without Requiring Michael Acceptor Reactivity","volume":"56","author":"Budke","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.bcp.2014.07.033","article-title":"Identification and characterization of human Rad51 inhibitors by screening of an existing drug library","volume":"91","author":"Normand","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"15848","DOI":"10.1073\/pnas.0808046105","article-title":"A chemical compound that stimulates the human homologous recombination protein RAD51","volume":"105","author":"Jayathilaka","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Huang, F., and Mazin, A.V. (2014). A Small Molecule Inhibitor of Human RAD51 Potentiates Breast Cancer Cell Killing by Therapeutic Agents in Mouse Xenografts. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100993"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1021\/jm201173g","article-title":"Inhibition of Homologous Recombination in Human Cells by Targeting RAD51 Recombinase","volume":"55","author":"Huang","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.chembiol.2015.10.003","article-title":"Small-Molecule Disruption of RAD52 Rings as a Mechanism for Precision Medicine in BRCA-Deficient Cancers","volume":"22","author":"Chandramouly","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.1093\/nar\/gkw087","article-title":"Targeting BRCA1- and BRCA2-deficient cells with RAD52 small molecule inhibitors","volume":"44","author":"Huang","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Sullivan, K., Cramer-Morales, K., McElroy, D.L., Ostrov, D.A., Haas, K., Childers, W., Hromas, R., and Skorski, T. (2016). Identification of a Small Molecule Inhibitor of RAD52 by Structure-Based Selection. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147230"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e14740","DOI":"10.7554\/eLife.14740","article-title":"Small-molecule inhibitors identify the RAD52-ssDNA interaction as critical for recovery from replication stress and for survival of BRCA2 deficient cells","volume":"5","author":"Hengel","year":"2016","journal-title":"eLife"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Raimundo, L., Paterna, A., Calheiros, J., Ribeiro, J., Cardoso, D.S.P., Piga, I., Neto, S.J., Hegan, D., Glazer, P.M., and Indraccolo, S. (2021). BBIT20 inhibits homologous DNA repair with disruption of the BRCA1\u2013BARD1 interaction in breast and ovarian cancer. Br. J. Pharmacol.","DOI":"10.1111\/bph.15506"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"31567","DOI":"10.1074\/jbc.M113.502195","article-title":"Analysis of the Activities of RAD54, a SWI2\/SNF2 Protein, Using a Specific Small-molecule Inhibitor","volume":"288","author":"Deakyne","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1073\/pnas.1006423108","article-title":"Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress","volume":"108","author":"Aggarwal","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"5497","DOI":"10.1158\/0008-5472.CAN-12-2975","article-title":"Werner Syndrome Helicase Has a Critical Role in DNA Damage Responses in the Absence of a Functional Fanconi Anemia Pathway","volume":"73","author":"Aggarwal","year":"2013","journal-title":"Cancer Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"5660","DOI":"10.1016\/j.bmcl.2013.08.025","article-title":"Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase","volume":"23","author":"Rosenthal","year":"2013","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nchembio.63","article-title":"A forward chemical genetic screen reveals an inhibitor of the Mre11\u2013Rad50\u2013Nbs1 complex","volume":"4","author":"Sattler","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.molcel.2013.11.003","article-title":"DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities","volume":"53","author":"Shibata","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"8421","DOI":"10.1002\/anie.201405169","article-title":"Discovery of Cell-Permeable Inhibitors That Target the BRCT Domain of BRCA1 Protein by Using a Small-Molecule Microarray","volume":"53","author":"Na","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1021\/ml200147a","article-title":"Exploiting the P-1 Pocket of BRCT Domains Toward a Structure Guided Inhibitor Design","volume":"2","author":"Yuan","year":"2011","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"5546","DOI":"10.1158\/0008-5472.CAN-10-3423","article-title":"p53-Dependent BRCA1 Nuclear Export Controls Cellular Susceptibility to DNA Damage","volume":"71","author":"Jiang","year":"2011","journal-title":"Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/14\/3438\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:28:09Z","timestamp":1760164089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/14\/3438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,9]]},"references-count":174,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cancers13143438"],"URL":"https:\/\/doi.org\/10.3390\/cancers13143438","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,9]]}}}