{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T19:40:20Z","timestamp":1768678820287,"version":"3.49.0"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["260203"],"award-info":[{"award-number":["260203"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["256790"],"award-info":[{"award-number":["256790"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background and purpose<\/jats:title>\n<jats:p>PARP inhibitors have been shown to increase the efficacy of radiotherapy in preclinical models. Radioimmunotherapy results in selective radiation cytotoxicity of targeted tumour cells. Here we investigate the combined effect of anti-CD37 \u03b2-emitting <jats:sup>177<\/jats:sup>Lu-NNV003 radioimmunotherapy and the PARP inhibitor olaparib, and gene expression profiles in CD37 positive non-Hodgkin\u2019s lymphoma cell lines.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>The combined effect of <jats:sup>177<\/jats:sup>Lu-NNV003 and olaparib was studied in seven cell lines using a fixed-ratio ray design, and combination index was calculated for each combination concentration. mRNA was extracted before and after treatment with the drug combination. After RNA-sequencing, hierarchical clustering was performed on basal gene expression profiles and on differentially expressed genes after combination treatment from baseline. Functional gene annotation analysis of significant differentially expressed genes after combination treatment was performed to identify enriched biological processes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The combination of olaparib and <jats:sup>177<\/jats:sup>Lu-NNV003 was synergistic in four of seven cell lines, antagonistic in one and both synergistic and antagonistic (conditionally synergistic) in two, depending on the concentration ratio between olaparib and <jats:sup>177<\/jats:sup>Lu-NNV003. Cells treated with the combination significantly overexpressed genes in the TP53 signalling pathway. However, cluster analysis did not identify gene clusters that correlate with the sensitivity of cells to single agent or combination treatment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The cytotoxic effect of the combination of the PARP inhibitor olaparib and the \u03b2-emitting radioimmunoconjugate <jats:sup>177<\/jats:sup>Lu-NNV003 was synergistic in the majority of tested lymphoma cell lines.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0267543","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T17:30:11Z","timestamp":1651253411000},"page":"e0267543","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anti-CD37 radioimmunotherapy with 177Lu-NNV003 synergizes with the PARP inhibitor olaparib in treatment of non-Hodgkin\u2019s lymphoma in vitro"],"prefix":"10.1371","volume":"17","author":[{"given":"Marion M.","family":"Malenge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5282-6571","authenticated-orcid":true,"given":"Astri Fjelde","family":"Maaland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5390-0692","authenticated-orcid":true,"given":"Ada","family":"Repetto-Llamazares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Middleton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Nijland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Visser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Patzke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Heyerdahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arne","family":"Kolstad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trond","family":"Stokke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-3223","authenticated-orcid":true,"given":"Anne Hansen","family":"Ree","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jostein","family":"Dahle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"issue":"20","key":"pone.0267543.ref001","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 revision of the World Health Organization classification of lymphoid neoplasms","volume":"127","author":"SH Swerdlow","year":"2016","journal-title":"Blood"},{"issue":"8","key":"pone.0267543.ref002","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1158\/1535-7163.MCT-15-0945","article-title":"ATM Mutations in Cancer: Therapeutic Implications","volume":"15","author":"M Choi","year":"2016","journal-title":"Mol Cancer Ther"},{"issue":"12","key":"pone.0267543.ref003","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.18632\/aging.100855","article-title":"The PTEN tumor suppressor gene and its role in lymphoma pathogenesis","volume":"7","author":"X Wang","year":"2015","journal-title":"Aging"},{"issue":"16","key":"pone.0267543.ref004","doi-asserted-by":"crossref","first-page":"3668","DOI":"10.1182\/blood-2011-11-366062","article-title":"Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies","volume":"119","author":"ZY Xu-Monette","year":"2012","journal-title":"Blood"},{"key":"pone.0267543.ref005","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-pharmtox-010814-124511","article-title":"Synthetic lethal vulnerabilities of cancer","volume":"55","author":"F Fece de la Cruz","year":"2015","journal-title":"Annual review of pharmacology and toxicology"},{"issue":"3","key":"pone.0267543.ref006","doi-asserted-by":"crossref","DOI":"10.1016\/j.ccell.2019.07.007","article-title":"LMO2 Confers Synthetic Lethality to PARP Inhibition in DLBCL","volume":"36","author":"S Parvin","year":"2019","journal-title":"Cancer Cell"},{"key":"pone.0267543.ref007","first-page":"217","volume":"211","author":"S Bochum","year":"2018","journal-title":"Olaparib. Recent results in cancer research Fortschritte der Krebsforschung Progres dans les recherches sur le cancer"},{"key":"pone.0267543.ref008","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12916-015-0425-1","article-title":"PARP inhibitors in the management of breast cancer: current data and future prospects","volume":"13","author":"L Livraghi","year":"2015","journal-title":"BMC Med"},{"issue":"2","key":"pone.0267543.ref009","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1158\/1535-7163.MCT-09-0872","article-title":"ATM Deficiency Sensitizes Mantle Cell Lymphoma Cells to Poly(ADP-Ribose) Polymerase-1 Inhibitors","volume":"9","author":"CT Williamson","year":"2010","journal-title":"Molecular Cancer Therapeutics"},{"key":"pone.0267543.ref010","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.critrevonc.2016.08.008","article-title":"ATM mutation and radiosensitivity: An opportunity in the therapy of mantle cell lymphoma","volume":"107","author":"M Ahmed","year":"2016","journal-title":"Crit Rev Oncol Hematol"},{"issue":"9","key":"pone.0267543.ref011","doi-asserted-by":"crossref","first-page":"5372","DOI":"10.1073\/pnas.0831102100","article-title":"Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma","volume":"100","author":"NY Fang","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pone.0267543.ref012","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1182\/blood-2002-02-0382","article-title":"ATM mutations are associated with inactivation of theARF-TP53 tumor suppressor pathway in diffuse large B-cell lymphoma","volume":"100","author":"K Gr\u00f8nb\u00e6k","year":"2002","journal-title":"Blood"},{"issue":"15","key":"pone.0267543.ref013","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.1158\/1078-0432.CCR-16-3068","article-title":"The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma","volume":"23","author":"JD Soumerai","year":"2017","journal-title":"Clin Cancer Res"},{"issue":"10","key":"pone.0267543.ref014","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1158\/1535-7163.MCT-11-0278","article-title":"Inhibition of PARP-1 by Olaparib (AZD2281) Increases the Radiosensitivity of a Lung Tumor Xenograft","volume":"10","author":"JM Senra","year":"2011","journal-title":"Molecular Cancer Therapeutics"},{"issue":"12","key":"pone.0267543.ref015","doi-asserted-by":"crossref","first-page":"984","DOI":"10.18632\/oncotarget.362","article-title":"PARP inhibition sensitizes childhood high grade glioma, medulloblastoma and ependymoma to radiation","volume":"2","author":"DG van Vuurden","year":"2011","journal-title":"Oncotarget"},{"issue":"11","key":"pone.0267543.ref016","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1158\/1535-7163.MCT-13-0010","article-title":"PARP1 Is Overexpressed in Nasopharyngeal Carcinoma and Its Inhibition Enhances Radiotherapy","volume":"12","author":"JPH Chow","year":"2013","journal-title":"Molecular Cancer Therapeutics"},{"issue":"3","key":"pone.0267543.ref017","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.radonc.2015.08.003","article-title":"In vivo studies of the PARP inhibitor, AZD-2281, in combination with fractionated radiotherapy: An exploration of the therapeutic ratio","volume":"116","author":"C Gani","year":"2015","journal-title":"Radiother Oncol"},{"issue":"3","key":"pone.0267543.ref018","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.radonc.2015.03.028","article-title":"Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells","volume":"116","author":"CVM Verhagen","year":"2015","journal-title":"Radiotherapy and Oncology"},{"issue":"5","key":"pone.0267543.ref019","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1667\/RR15035.1","article-title":"Enhancement of Soft Tissue Sarcoma Cell Radiosensitivity by Poly(ADP-ribose) Polymerase-1 Inhibitors","volume":"190","author":"M Mangoni","year":"2018","journal-title":"Radiation Research"},{"issue":"4","key":"pone.0267543.ref020","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1002\/cam4.1318","article-title":"PARP inhibitor olaparib sensitizes cholangiocarcinoma cells to radiation","volume":"7","author":"YZ Mao","year":"2018","journal-title":"Cancer Medicine"},{"issue":"2","key":"pone.0267543.ref021","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1158\/1541-7786.MCR-17-0455","article-title":"PARP1 Trapping and DNA Replication Stress Enhance Radiosensitization with Combined WEE1 and PARP Inhibitors","volume":"16","author":"LA Parsels","year":"2018","journal-title":"Molecular Cancer Research"},{"key":"pone.0267543.ref022","first-page":"16","article-title":"An evaluation in vitro of PARP-1 inhibitors, rucaparib and olaparib, as radiosensitisers for the treatment of neuroblastoma","author":"DL Nile","year":"2016","journal-title":"Bmc Cancer"},{"issue":"7","key":"pone.0267543.ref023","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/jphp.12558","article-title":"Preliminary evaluation of prostate-targeted radiotherapy using I-131-MIP-1095 in combination with radiosensitising chemotherapeutic drugs","volume":"68","author":"M Tesson","year":"2016","journal-title":"Journal of Pharmacy and Pharmacology"},{"issue":"11","key":"pone.0267543.ref024","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1097\/MNM.0b013e32834a369b","article-title":"Poly(ADP-ribose) polymerase inhibitors combined with external beam and radioimmunotherapy to treat aggressive lymphoma","volume":"32","author":"NG Schaefer","year":"2011","journal-title":"Nucl Med Commun"},{"issue":"Supplement_1","key":"pone.0267543.ref025","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1182\/blood-2019-130427","article-title":"Addition of the PARP Inhibitor, Talazoparib, to Gemtuzumab Ozogamicin Significantly Enhances Anti-Leukemic Activity in Human CD33+ Acute Myeloid Leukemia","volume":"134","author":"SM Portwood","year":"2019","journal-title":"Blood"},{"key":"pone.0267543.ref026","article-title":"Final Report of a Phase I Trial of Olaparib with Cetuximab and Radiation for Heavy Smoker Patients with Locally Advanced Head and Neck Cancer","author":"SD Karam","year":"2018","journal-title":"Clinical Cancer Research"},{"key":"pone.0267543.ref027","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ctro.2017.11.003","article-title":"PARADIGM-2: Two parallel phase I studies of olaparib and radiotherapy or olaparib and radiotherapy plus temozolomide in patients with newly diagnosed glioblastoma, with treatment stratified by MGMT status","volume":"8","author":"B Fulton","year":"2018","journal-title":"Clin Transl Radiat Oncol"},{"issue":"1","key":"pone.0267543.ref028","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1186\/s12885-019-6121-3","article-title":"Study protocols of three parallel phase 1 trials combining radical radiotherapy with the PARP inhibitor olaparib","volume":"19","author":"R de Haan","year":"2019","journal-title":"BMC Cancer"},{"issue":"1","key":"pone.0267543.ref029","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s12885-019-5413-y","article-title":"Phase I\/IIa study of concomitant radiotherapy with olaparib and temozolomide in unresectable or partially resectable glioblastoma: OLA-TMZ-RTE-01 trial protocol","volume":"19","author":"P Lesueur","year":"2019","journal-title":"BMC Cancer"},{"issue":"11","key":"pone.0267543.ref030","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1007\/s00259-019-04417-1","article-title":"Targeting B-cell malignancies with the beta-emitting anti-CD37 radioimmunoconjugate 177Lu-NNV003","volume":"46","author":"AF Maaland","year":"2019","journal-title":"European Journal of Nuclear Medicine and Molecular Imaging"},{"issue":"1","key":"pone.0267543.ref031","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0022-1759(84)90435-6","article-title":"Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess","volume":"72","author":"T Lindmo","year":"1984","journal-title":"J Immunol Methods"},{"issue":"1","key":"pone.0267543.ref032","doi-asserted-by":"crossref","first-page":"12046","DOI":"10.1038\/s41598-018-30509-3","article-title":"Drug-based perturbation screen uncovers synergistic drug combinations in Burkitt lymphoma","volume":"8","author":"K Tomska","year":"2018","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0267543.ref033","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s11523-016-0435-8","article-title":"An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib","volume":"11","author":"J Mateo","year":"2016","journal-title":"Target Oncol"},{"issue":"3","key":"pone.0267543.ref034","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/bimj.200410124","article-title":"Design and Analysis of Drug Combination Experiments","volume":"47","author":"R Straetemans","year":"2005","journal-title":"Biometrical Journal"},{"issue":"3","key":"pone.0267543.ref035","doi-asserted-by":"crossref","first-page":"e00149","DOI":"10.1002\/prp2.149","article-title":"Analysis of drug combinations: current methodological landscape","volume":"3","author":"J Foucquier","year":"2015","journal-title":"Pharmacol Res Perspect"},{"issue":"3","key":"pone.0267543.ref036","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1124\/jpet.104.067264","article-title":"Isobolographic analysis for combinations of a full and partial agonist: curved isoboles","volume":"310","author":"Y Grabovsky","year":"2004","journal-title":"J Pharmacol Exp Ther"},{"issue":"9","key":"pone.0267543.ref037","doi-asserted-by":"crossref","first-page":"R183","DOI":"10.1186\/gb-2007-8-9-r183","article-title":"The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists","volume":"8","author":"DW Huang","year":"2007","journal-title":"Genome biology"},{"key":"pone.0267543.ref038","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.3389\/fonc.2019.01301","article-title":"The Dual Cell Cycle Kinase Inhibitor JNJ-7706621 Reverses Resistance to CD37-Targeted Radioimmunotherapy in Activated B Cell Like Diffuse Large B Cell Lymphoma Cell Lines","volume":"9","author":"GE Rodland","year":"2019","journal-title":"Front Oncol"},{"issue":"10","key":"pone.0267543.ref039","doi-asserted-by":"crossref","DOI":"10.3390\/cancers11101475","article-title":"The Role of the Cyclin Dependent Kinase Inhibitor p21(cip1\/waf1) in Targeting Cancer: Molecular Mechanisms and Novel Therapeutics","volume":"11","author":"S Al Bitar","year":"2019","journal-title":"Cancers"},{"issue":"26","key":"pone.0267543.ref040","doi-asserted-by":"crossref","first-page":"10690","DOI":"10.1073\/pnas.0812254106","article-title":"DDB2 decides cell fate following DNA damage","volume":"106","author":"T Stoyanova","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"pone.0267543.ref041","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.1038\/ncomms4695","article-title":"Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity","volume":"5","author":"MR Puumalainen","year":"2014","journal-title":"Nature communications"},{"issue":"49","key":"pone.0267543.ref042","doi-asserted-by":"crossref","first-page":"6762","DOI":"10.1038\/onc.2017.254","article-title":"Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2\/M phase","volume":"36","author":"LE Giono","year":"2017","journal-title":"Oncogene"},{"issue":"10","key":"pone.0267543.ref043","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/emmm.201000097","article-title":"Stressin\u2019 Sestrins take an aging fight","volume":"2","author":"AV Budanov","year":"2010","journal-title":"EMBO Mol Med"},{"issue":"2","key":"pone.0267543.ref044","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.bbrc.2008.02.047","article-title":"Human DDA3 is an oncoprotein down-regulated by p53 and DNA damage","volume":"369","author":"WJ Hsieh","year":"2008","journal-title":"Biochemical and biophysical research communications"},{"issue":"2","key":"pone.0267543.ref045","first-page":"190","article-title":"PLK-1: Angel or devil for cell cycle progression","volume":"1865","author":"S Kumar","year":"2016","journal-title":"Biochimica et biophysica acta"},{"issue":"2\u20134","key":"pone.0267543.ref046","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ejcb.2018.12.002","article-title":"Roles and mechanisms of Kinesin-6 KIF20A in spindle organization during cell division","volume":"98","author":"WD Wu","year":"2019","journal-title":"European journal of cell biology"},{"issue":"16","key":"pone.0267543.ref047","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":"N McCabe","year":"2006","journal-title":"Cancer Res"},{"issue":"2","key":"pone.0267543.ref048","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nrc.2015.21","article-title":"BRCAness revisited","volume":"16","author":"CJ Lord","year":"2016","journal-title":"Nat Rev Cancer"},{"issue":"7713","key":"pone.0267543.ref049","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41586-018-0291-z","article-title":"CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions","volume":"559","author":"M Zimmermann","year":"2018","journal-title":"Nature"},{"issue":"3","key":"pone.0267543.ref050","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.ijrobp.2009.04.062","article-title":"In vitro cytotoxicity of low-dose-rate radioimmunotherapy by the alpha-emitting radioimmunoconjugate Thorium-227-DOTA-rituximab","volume":"75","author":"J Dahle","year":"2009","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"19","key":"pone.0267543.ref051","doi-asserted-by":"crossref","first-page":"6935","DOI":"10.1088\/0031-9155\/61\/19\/6935","article-title":"Realistic multi-cellular dosimetry for (177)Lu-labelled antibodies: model and application","volume":"61","author":"S Marcatili","year":"2016","journal-title":"Phys Med Biol"},{"key":"pone.0267543.ref052","unstructured":"Center NND. National Nuclear Data Center, ENSDF Decay Data in the MIRD (Medical Internal Radiation Dose) Format for 177Lu 2012 [updated 10\/16\/2012; cited 2012 10\/16\/2012]. Available from: http:\/\/www.nndc.bnl.gov\/useroutput\/177lu_mird.html."},{"issue":"16","key":"pone.0267543.ref053","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1038\/sj.onc.1202632","article-title":"Induced p21waf expression in H1299 cell line promotes cell senescence and protects against cytotoxic effect of radiation and doxorubicin","volume":"18","author":"Y Wang","year":"1999","journal-title":"Oncogene"},{"issue":"52","key":"pone.0267543.ref054","doi-asserted-by":"crossref","first-page":"19842","DOI":"10.1073\/pnas.0606343104","article-title":"p21 delays tumor onset by preservation of chromosomal stability","volume":"103","author":"JA Barboza","year":"2006","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"6303","key":"pone.0267543.ref055","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/348747a0","article-title":"Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li\u2013Fraumeni syndrome","volume":"348","author":"S Srivastava","year":"1990","journal-title":"Nature"},{"issue":"4","key":"pone.0267543.ref056","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S1535-6108(03)00079-5","article-title":"p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis","volume":"3","author":"D Bergamaschi","year":"2003","journal-title":"Cancer Cell"},{"issue":"10","key":"pone.0267543.ref057","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.neo.2015.10.003","article-title":"Specific TP53 Mutants Overrepresented in Ovarian Cancer Impact CNV, TP53 Activity, Responses to Nutlin-3a, and Cell Survival","volume":"17","author":"LK Mullany","year":"2015","journal-title":"Neoplasia"},{"issue":"1","key":"pone.0267543.ref058","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/ng0997-96","article-title":"Clustering of missense mutations in the ataxia-telanglectasia gene in a sporadic T-cell leukaemia","volume":"17","author":"I Vo\u0159echovsk\u00fd","year":"1997","journal-title":"Nature Genetics"},{"issue":"2","key":"pone.0267543.ref059","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1006\/mgme.2000.2998","article-title":"Ataxia-telangiectasia: phenotype\/genotype studies of ATM protein expression, mutations, and radiosensitivity","volume":"70","author":"SG Becker-Catania","year":"2000","journal-title":"Mol Genet Metab"},{"issue":"8","key":"pone.0267543.ref060","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1002\/humu.21034","article-title":"Modeling ATM mutant proteins from missense changes confirms retained kinase activity","volume":"30","author":"G Barone","year":"2009","journal-title":"Hum Mutat"},{"issue":"1","key":"pone.0267543.ref061","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/humu.20805","article-title":"Functional and computational assessment of missense variants in the ataxia-telangiectasia mutated (ATM) gene: mutations with increased cancer risk","volume":"30","author":"M Mitui","year":"2009","journal-title":"Hum Mutat"},{"issue":"6","key":"pone.0267543.ref062","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/emmm.201200229","article-title":"Enhanced cytotoxicity of PARP inhibition in mantle cell lymphoma harbouring mutations in both ATM and p53","volume":"4","author":"CT Williamson","year":"2012","journal-title":"EMBO Mol Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0267543","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T17:31:17Z","timestamp":1651253477000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0267543"}},"subtitle":[],"editor":[{"given":"Irina V.","family":"Lebedeva","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,4,29]]},"references-count":62,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0267543","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,29]]}}}