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Despite advances in multimodality treatment, the disease has a recurrence rate of around 50%, and the prognosis of metastatic patients remains poor. HNCs are characterized by a high degree of genomic instability, which involves a vicious circle of accumulating DNA damage, defective DNA damage repair (DDR), and replication stress. Nonetheless, the damage that is induced on tumor cells by chemo and radiotherapy relies on defective DDR processes for a successful response to treatment, and may play an important role in the development of novel and more effective therapies. This review summarizes the current knowledge on the genes and proteins that appear to be deregulated in DDR pathways, their implication in HNC pathogenesis, and the rationale behind targeting these genes and pathways for the development of new therapies. We give particular emphasis on the therapeutic targets that have shown promising results at the pre-clinical stage and on those that have so far been associated with a therapeutic advantage in the clinical setting.<\/jats:p>","DOI":"10.3390\/ijms24032760","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T05:04:48Z","timestamp":1675227888000},"page":"2760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["DNA Damage Response Mechanisms in Head and Neck Cancer: Significant Implications for Therapy and Survival"],"prefix":"10.3390","volume":"24","author":[{"given":"Chara","family":"Papalouka","sequence":"first","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8779-4485","authenticated-orcid":false,"given":"Maria","family":"Adamaki","sequence":"additional","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Batsaki","sequence":"additional","affiliation":[{"name":"Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Zoumpourlis","sequence":"additional","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Tsintarakis","sequence":"additional","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9596-5048","authenticated-orcid":false,"given":"Maria","family":"Goulielmaki","sequence":"additional","affiliation":[{"name":"Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios P.","family":"Fortis","sequence":"additional","affiliation":[{"name":"Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0324-7378","authenticated-orcid":false,"given":"Constantin N.","family":"Baxevanis","sequence":"additional","affiliation":[{"name":"Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 11522 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilis","family":"Zoumpourlis","sequence":"additional","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1097\/CCO.0000000000000629","article-title":"Epidemiology of head and neck cancers: An update","volume":"32","author":"Auperin","year":"2020","journal-title":"Curr. Opin. Oncol."},{"key":"ref_3","unstructured":"Global Burden of Disease Cancer Collaboration, Fitzmaurice, C., Abate, D., Abbasi, N., Abbastabar, H., Abd-Allah, F., Abdel-Rahman, O., Abdelalim, A., Abdoli, A., and Abdollahpour, I. (2019). Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol., 5, 1749\u20131768."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"394","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_6","doi-asserted-by":"crossref","first-page":"717084","DOI":"10.3389\/fsurg.2021.717084","article-title":"Identification of a Novel Signature Predicting Overall Survival in Head and Neck Squamous Cell Carcinoma","volume":"8","author":"Zheng","year":"2021","journal-title":"Front. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1080\/10590500802129431","article-title":"Genetic and environmental factors in head and neck cancer genesis","volume":"26","author":"Baez","year":"2008","journal-title":"J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1093\/jnci\/djk179","article-title":"Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium","volume":"99","author":"Hashibe","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s10555-017-9690-0","article-title":"Alcohol and head and neck cancer","volume":"36","author":"Kawakita","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"pky045","DOI":"10.1093\/jncics\/pky045","article-title":"Burden of Human Papillomavirus (HPV)-Related Cancers Attributable to HPVs 6\/11\/16\/18\/31\/33\/45\/52 and 58","volume":"2","author":"Serrano","year":"2018","journal-title":"JNCI Cancer Spectr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100075","DOI":"10.1016\/j.esmoop.2021.100075","article-title":"The DNA damage response network in the treatment of head and neck squamous cell carcinoma","volume":"6","author":"Psyrri","year":"2021","journal-title":"ESMO Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1056\/NEJMoa032646","article-title":"Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck","volume":"350","author":"Cooper","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_13","first-page":"464720","article-title":"Genome stability pathways in head and neck cancers","volume":"2013","author":"Jenkins","year":"2013","journal-title":"Int. J. Genom."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1007\/s00405-013-2749-9","article-title":"Weekly cisplatin concurrently with radiotherapy in head and neck squamous cell cancer: A retrospective analysis of a tertiary institute experience","volume":"271","author":"Osman","year":"2014","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5393","DOI":"10.21873\/anticanres.15351","article-title":"DNA Double-strand Break Signaling Is a Therapeutic Target in Head and Neck Cancer","volume":"41","author":"Wu","year":"2021","journal-title":"Anticancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41571-019-0227-z","article-title":"The changing therapeutic landscape of head and neck cancer","volume":"16","author":"Cramer","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.1200\/JCO.2015.61.1509","article-title":"Immunology and Immunotherapy of Head and Neck Cancer","volume":"33","author":"Ferris","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1056\/NEJMra1715715","article-title":"Head and Neck Cancer","volume":"382","author":"Chow","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16134","DOI":"10.1038\/s41598-021-95718-9","article-title":"Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma","volume":"11","author":"Mito","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1055-3207(03)00118-2","article-title":"The role of genomic instability in the pathogenesis of squamous cell carcinoma of the head and neck","volume":"13","author":"Wiseman","year":"2004","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1177\/1535370219826031","article-title":"Role of genomic instability in human carcinogenesis","volume":"244","author":"Moon","year":"2019","journal-title":"Exp. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R285","DOI":"10.1016\/j.cub.2010.01.034","article-title":"Mechanisms of chromosomal instability","volume":"20","author":"Thompson","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-387688-1.00001-6","article-title":"Intratumor diversity and clonal evolution in cancer\u2014A skeptical standpoint","volume":"112","author":"Gisselsson","year":"2011","journal-title":"Adv. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1158\/0008-5472.CAN-07-5835","article-title":"Cancers exhibit a mutator phenotype: Clinical implications","volume":"68","author":"Loeb","year":"2008","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1126\/science.1140735","article-title":"An oncogene-induced DNA damage model for cancer development","volume":"319","author":"Halazonetis","year":"2008","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nature03485","article-title":"Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions","volume":"434","author":"Gorgoulis","year":"2005","journal-title":"Nature"},{"key":"ref_27","first-page":"307","article-title":"Genomic Instability, DNA Alterations and Tumor Eosinophilic Expression in Head and Neck Squamous Cell Carcinoma","volume":"2","author":"Alrawi","year":"2005","journal-title":"Cancer Genom. Proteom."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1089\/dna.2011.1325","article-title":"Evaluation of DNA double strand breaks repair efficiency in head and neck cancer","volume":"31","author":"Walczak","year":"2012","journal-title":"DNA Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1093\/nar\/gkq1175","article-title":"CtIP and MRN promote non-homologous end-joining of etoposide-induced DNA double-strand breaks in G1","volume":"39","author":"Quennet","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/abbs\/gmx055","article-title":"Cell cycle-dependent control of homologous recombination","volume":"49","author":"Zhao","year":"2017","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/PPO.0b013e318292e4e3","article-title":"Basic mechanisms of therapeutic resistance to radiation and chemotherapy in lung cancer","volume":"19","author":"Willers","year":"2013","journal-title":"Cancer J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.3390\/cancers6031769","article-title":"Drug resistance in cancer: An overview","volume":"6","author":"Housman","year":"2014","journal-title":"Cancers"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1002\/cam4.2056","article-title":"SALL4 induces radioresistance in nasopharyngeal carcinoma via the ATM\/Chk2\/p53 pathway","volume":"8","author":"Nie","year":"2019","journal-title":"Cancer Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109748","DOI":"10.1016\/j.biopha.2019.109748","article-title":"CHAF1B induces radioresistance by promoting DNA damage repair in nasopharyngeal carcinoma","volume":"123","author":"Di","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"408","DOI":"10.7150\/ijbs.37302","article-title":"The Homologous Recombination Repair Pathway is Associated with Resistance to Radiotherapy in Nasopharyngeal Carcinoma","volume":"16","author":"Wang","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lodovichi, S., Cervelli, T., Pellicioli, A., and Galli, A. (2020). Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186684"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1111\/bph.12244","article-title":"Inhibiting the DNA damage response as a therapeutic manoeuvre in cancer","volume":"169","author":"Curtin","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","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":"Chow","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"787766","DOI":"10.3389\/fcell.2021.787766","article-title":"Identification and Validation of a Novel Genomic Instability-Associated Long Non-Coding RNA Prognostic Signature in Head and Neck Squamous Cell Carcinoma","volume":"9","author":"Chen","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s10555-013-9429-5","article-title":"The detection and implication of genome instability in cancer","volume":"32","author":"Pikor","year":"2013","journal-title":"Cancer Metastasis Rev."},{"key":"ref_41","first-page":"989","article-title":"DNA mismatch repair, microsatellite instability and cancer","volume":"40","author":"Vaish","year":"2002","journal-title":"Indian J. Exp. Biol."},{"key":"ref_42","first-page":"202","article-title":"Somatic mutation signatures of cancer","volume":"2008","author":"Piccolo","year":"2008","journal-title":"AMIA Annu. Symp. Proc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/nrc1190","article-title":"Tobacco carcinogens, their biomarkers and tobacco-induced cancer","volume":"3","author":"Hecht","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11431","DOI":"10.1039\/C7DT01358B","article-title":"Synthesis of mesoporous iridium nanosponge: A highly active, thermally stable and efficient olefin hydrogenation catalyst","volume":"46","author":"Ghosh","year":"2017","journal-title":"Dalton Trans."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4103\/0973-029X.57677","article-title":"Gorlin-Goltz syndrome","volume":"13","author":"Jawa","year":"2009","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100","DOI":"10.4103\/1735-3327.92963","article-title":"Gorlin-Goltz syndrome","volume":"9","author":"Joshi","year":"2012","journal-title":"Dent. Res. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3892\/br.2021.1450","article-title":"An update on Fanconi anemia: Clinical, cytogenetic and molecular approaches (Review)","volume":"15","author":"Moreno","year":"2021","journal-title":"Biomed. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Garcia-de-Teresa, B., Rodriguez, A., and Frias, S. (2020). Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences. Genes, 11.","DOI":"10.20944\/preprints202011.0563.v2"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Powell, S.F., Vu, L., Spanos, W.C., and Pyeon, D. (2021). The Key Differences between Human Papillomavirus-Positive and -Negative Head and Neck Cancers: Biological and Clinical Implications. Cancers, 13.","DOI":"10.3390\/cancers13205206"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrc1295","article-title":"Dynamics of cancer progression","volume":"4","author":"Michor","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1158\/0008-5472.CAN-18-3631","article-title":"Exploiting DNA Replication Stress for Cancer Treatment","volume":"79","author":"Ubhi","year":"2019","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nsmb.2543","article-title":"Transcription-replication encounters, consequences and genomic instability","volume":"20","author":"Helmrich","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Billard, P., and Poncet, D.A. (2019). Replication Stress at Telomeric and Mitochondrial DNA: Common Origins and Consequences on Ageing. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194959"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/ncb2897","article-title":"Causes and consequences of replication stress","volume":"16","author":"Zeman","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.yexcr.2014.09.030","article-title":"DNA replication stress: Causes, resolution and disease","volume":"329","author":"Mazouzi","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.tig.2011.10.003","article-title":"Common fragile sites: Mechanisms of instability revisited","volume":"28","author":"Debatisse","year":"2012","journal-title":"Trends Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/mutage\/geh025","article-title":"Endogenous DNA damage in humans: A review of quantitative data","volume":"19","year":"2004","journal-title":"Mutagenesis"},{"key":"ref_58","first-page":"476","article-title":"Cancers of the lung, head and neck on the rise: Perspectives on the genotoxicity of air pollution","volume":"33","author":"Wong","year":"2014","journal-title":"Chin. J. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1002\/ijc.31416","article-title":"Tobacco smoking and alcohol drinking at diagnosis of head and neck cancer and all-cause mortality: Results from head and neck 5000, a prospective observational cohort of people with head and neck cancer","volume":"143","author":"Beynon","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1038\/s41416-020-01031-z","article-title":"Alcohol drinking and head and neck cancer risk: The joint effect of intensity and duration","volume":"123","author":"Polesel","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1515\/reveh-2020-0109","article-title":"Exposure to cadmium and head and neck cancers: A meta-analysis of observational studies","volume":"36","author":"Rezapour","year":"2021","journal-title":"Rev. Environ. Health"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1158\/1940-6207.CAPR-17-0140","article-title":"High Level of Tobacco Carcinogen-Derived DNA Damage in Oral Cells Is an Independent Predictor of Oral\/Head and Neck Cancer Risk in Smokers","volume":"10","author":"Khariwala","year":"2017","journal-title":"Cancer Prev. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1158\/1940-6207.CAPR-21-0529","article-title":"Noxious Combination of Tobacco Smoke Nitrosamines with Bile, Deoxycholic Acid, Promotes Hypopharyngeal Squamous Cell Carcinoma, via NFkappaB, In Vivo","volume":"15","author":"Vageli","year":"2022","journal-title":"Cancer Prev. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e027","DOI":"10.1590\/1807-3107bor-2022.vol36.0027","article-title":"DNA damage-related proteins in smokers and non-smokers with oral cancer","volume":"36","author":"Schuch","year":"2022","journal-title":"Braz. Oral Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S1470-2045(07)70099-2","article-title":"Carcinogenicity of alcoholic beverages","volume":"8","author":"Baan","year":"2007","journal-title":"Lancet Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1002\/hed.27125","article-title":"Exposure to alcohol and overall survival in head and neck cancer: A regional cohort study","volume":"44","author":"Denissoff","year":"2022","journal-title":"Head Neck"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-3-319-09614-8_4","article-title":"Alcohol and cancer: An overview with special emphasis on the role of acetaldehyde and cytochrome P450 2E1","volume":"815","author":"Seitz","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"413","DOI":"10.7150\/jca.65400","article-title":"Impacts of Cigarette Smoking on the Tumor Immune Microenvironment in Esophageal Squamous Cell Carcinoma","volume":"13","author":"Wang","year":"2022","journal-title":"J. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1002\/mc.22344","article-title":"Areca nut contributes to oral malignancy through facilitating the conversion of cancer stem cells","volume":"55","author":"Li","year":"2016","journal-title":"Mol. Carcinog."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4054","DOI":"10.7150\/jca.29765","article-title":"Multifaceted Mechanisms of Areca Nuts in Oral Carcinogenesis: The Molecular Pathology from Precancerous Condition to Malignant Transformation","volume":"10","author":"Li","year":"2019","journal-title":"J. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wang, Y.C., Lee, K.W., Tsai, Y.S., Lu, H.H., Chen, S.Y., Hsieh, H.Y., and Lin, C.S. (2021). Downregulation of ATM and BRCA1 Predicts Poor Outcome in Head and Neck Cancer: Implications for ATM-Targeted Therapy. J. Pers. Med., 11.","DOI":"10.3390\/jpm11050389"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1159\/000477255","article-title":"Head and Neck Cancer\u2014New Insights into a Heterogeneous Disease","volume":"40","author":"Klussmann","year":"2017","journal-title":"Oncol. Res. Treat."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.wjorl.2016.05.007","article-title":"Intra-tumor heterogeneity in head and neck cancer and its clinical implications","volume":"2","author":"Mroz","year":"2016","journal-title":"World J. Otorhinolaryngol. Head Neck Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1158\/1078-0432.CCR-13-2585","article-title":"Reverse-phase protein array profiling of oropharyngeal cancer and significance of PIK3CA mutations in HPV(\u2212)associated head and neck cancer","volume":"20","author":"Sewell","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1158\/1078-0432.CCR-05-2017","article-title":"Gene expression differences associated with human papillomavirus status in head and neck squamous cell carcinoma","volume":"12","author":"Slebos","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/path.2227","article-title":"Gene expression profiles in HPV(\u2212)infected head and neck cancer","volume":"213","author":"Schlecht","year":"2007","journal-title":"J. Pathol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s41199-019-0042-3","article-title":"NSD1 mutations by HPV status in head and neck cancer: Differences in survival and response to DNA-damaging agents","volume":"4","author":"Pan","year":"2019","journal-title":"Cancers Head Neck"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gr.241141.118","article-title":"Human papillomavirus and the landscape of secondary genetic alterations in oral cancers","volume":"29","author":"Gillison","year":"2019","journal-title":"Genom. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"15544","DOI":"10.1073\/pnas.1416074111","article-title":"Characterization of HPV and host genome interactions in primary head and neck cancers","volume":"111","author":"Parfenov","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Network (2015). Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature, 517, 576\u2013582.","DOI":"10.1038\/nature14129"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Bamps, M., Dok, R., and Nuyts, S. (2021). The DNA Damage Response Is Differentially Involved in HPV(\u2212)Positive and HPV(\u2212)Negative Radioresistant Head and Neck Squamous Cell Carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13153717"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1002\/jcb.25592","article-title":"TP53 Mutations in Head and Neck Squamous Cell Carcinoma and Their Impact on Disease Progression and Treatment Response","volume":"117","author":"Zhou","year":"2016","journal-title":"J. Cell Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1126\/science.1208130","article-title":"The mutational landscape of head and neck squamous cell carcinoma","volume":"333","author":"Stransky","year":"2011","journal-title":"Science"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1126\/science.1206923","article-title":"Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1","volume":"333","author":"Agrawal","year":"2011","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1158\/0008-5472.CAN-06-3619","article-title":"Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head\/neck and cervical cancers","volume":"67","author":"Pyeon","year":"2007","journal-title":"Cancer Res."},{"key":"ref_86","first-page":"E3255","article-title":"Molecular transitions from papillomavirus infection to cervical precancer and cancer: Role of stromal estrogen receptor signaling","volume":"112","author":"Pyeon","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Hinic, S., Rich, A., Anayannis, N.V., Cabarcas-Petroski, S., Schramm, L., and Meneses, P.I. (2022). Gene Expression and DNA Methylation in Human Papillomavirus Positive and Negative Head and Neck Squamous Cell Carcinomas. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810967"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Ekanayake Weeramange, C., Tang, K.D., Vasani, S., Langton-Lockton, J., Kenny, L., and Punyadeera, C. (2020). DNA Methylation Changes in Human Papillomavirus-Driven Head and Neck Cancers. Cells, 9.","DOI":"10.3390\/cells9061359"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Hajek, M., Biktasova, A., Sewell, A., Gary, C., Cantalupo, P., Anderson, K.S., Yarbrough, W.G., and Issaeva, N. (2020). Global Genome Demethylation Causes Transcription-Associated DNA Double Strand Breaks in HPV(\u2212)Associated Head and Neck Cancer Cells. Cancers, 13.","DOI":"10.3390\/cancers13010021"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nrm.2016.48","article-title":"The Fanconi anaemia pathway: New players and new functions","volume":"17","author":"Ceccaldi","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"797880","DOI":"10.3389\/fimmu.2021.797880","article-title":"Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy","volume":"12","author":"Ye","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.tibs.2015.08.006","article-title":"Microhomology-Mediated End Joining: A Back-up Survival Mechanism or Dedicated Pathway?","volume":"40","author":"Sfeir","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13578-017-0136-8","article-title":"Microhomology-mediated end joining: New players join the team","volume":"7","author":"Wang","year":"2017","journal-title":"Cell Biosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21037\/pcm.2019.02.05","article-title":"Alternative non-homologous end joining repair: A master regulator of genomic instability in cancer","volume":"2","author":"Caracciolo","year":"2019","journal-title":"Precis. Cancer Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"a012609","DOI":"10.1101\/cshperspect.a012609","article-title":"Nucleotide excision repair in eukaryotes","volume":"5","author":"Scharer","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1615\/CritRevOncog.v13.i2.20","article-title":"Xeroderma pigmentosum: A glimpse into nucleotide excision repair, genetic instability, and cancer","volume":"13","author":"Dworaczek","year":"2007","journal-title":"Crit. Rev. Oncog."},{"key":"ref_97","first-page":"1","article-title":"Chapter 16 Mechanisms and Maps of Nucleotide Excision Repair","volume":"Volume 2","author":"Vaughn","year":"2021","journal-title":"DNA Damage, DNA Repair and Disease: Volume 2"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"561687","DOI":"10.3389\/fgene.2020.561687","article-title":"Xeroderma Pigmentosum C (XPC) Mutations in Primary Fibroblasts Impair Base Excision Repair Pathway and Increase Oxidative DNA Damage","volume":"11","author":"Fayyad","year":"2020","journal-title":"Front. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/cr.2007.115","article-title":"Mechanisms and functions of DNA mismatch repair","volume":"18","author":"Li","year":"2008","journal-title":"Cell Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"765968","DOI":"10.3389\/fonc.2022.765968","article-title":"A Lack of Effectiveness in the ATM-Orchestrated DNA Damage Response Contributes to the DNA Repair Defect of HPV(\u2212)Positive Head and Neck Cancer Cells","volume":"12","author":"Kocher","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5971","DOI":"10.1007\/s13277-014-1792-5","article-title":"Deregulation of base excision repair gene expression and enhanced proliferation in head and neck squamous cell carcinoma","volume":"35","author":"Mahjabeen","year":"2014","journal-title":"Tumour Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"a012716","DOI":"10.1101\/cshperspect.a012716","article-title":"DNA damage sensing by the ATM and ATR kinases","volume":"5","author":"Marechal","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.molcel.2017.05.015","article-title":"ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response","volume":"66","author":"Blackford","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/tpj.15567","article-title":"Cell cycle checkpoint control in response to DNA damage by environmental stresses","volume":"109","author":"Xiang","year":"2022","journal-title":"Plant J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1083\/jcb.200906064","article-title":"Autophosphorylation at serine 1981 stabilizes ATM at DNA damage sites","volume":"187","author":"So","year":"2009","journal-title":"J. Cell. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/ncb1599","article-title":"Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair","volume":"9","author":"Berkovich","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrc1011","article-title":"ATM and related protein kinases: Safeguarding genome integrity","volume":"3","author":"Shiloh","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1038\/sj.emboj.7601719","article-title":"Spreading of mammalian DNA-damage response factors studied by ChIP-chip at damaged telomeres","volume":"26","author":"Meier","year":"2007","journal-title":"EMBO J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.molcel.2009.04.012","article-title":"Formation of dynamic gamma-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin","volume":"34","author":"Savic","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/ncomms2008","article-title":"FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage","volume":"3","author":"Chung","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_111","unstructured":"Paolo Boffetta, P.H. (2019). Encyclopedia of Cancer, Academic Press. [3rd ed.]."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrc.2017.116","article-title":"Fanconi anaemia and cancer: An intricate relationship","volume":"18","author":"Nalepa","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1001\/archotol.129.1.106","article-title":"High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia","volume":"129","author":"Kutler","year":"2003","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_114","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":"Choi","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1158\/1055-9965.EPI-082-3","article-title":"Ataxia-telangiectasia-mutated (ATM) gene in head and neck squamous cell carcinoma: Promoter hypermethylation with clinical correlation in 100 cases","volume":"13","author":"Ai","year":"2004","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"10012","DOI":"10.1038\/s41598-021-89476-x","article-title":"Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy","volume":"11","author":"Hier","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Moody, C.A., and Laimins, L.A. (2009). Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000605"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1126\/science.1083430","article-title":"Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes","volume":"300","author":"Zou","year":"2003","journal-title":"Science"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1126\/science.aap9346","article-title":"An intrinsic S\/G2 checkpoint enforced by ATR","volume":"361","author":"Saldivar","year":"2018","journal-title":"Science"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1158\/2159-8290.CD-17-0151","article-title":"AACR Project GENIE: Powering Precision Medicine through an International Consortium","volume":"7","author":"Consortium","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S1535-6108(03)00110-7","article-title":"Chk1 and Chk2 kinases in checkpoint control and cancer","volume":"3","author":"Bartek","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_122","first-page":"4990","article-title":"DNA damage-activated kinase Chk2 is independent of proliferation or differentiation yet correlates with tissue biology","volume":"61","author":"Lukas","year":"2001","journal-title":"Cancer Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/B978-0-12-380888-2.00003-0","article-title":"The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer","volume":"108","author":"Smith","year":"2010","journal-title":"Adv. Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"106152","DOI":"10.1016\/j.biocel.2021.106152","article-title":"Proline-serine-threonine-repeat region of MDC1 mediates Chk1 phosphorylation and the DNA double-strand break repair","volume":"143","author":"Choi","year":"2022","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e00472-17","DOI":"10.1128\/MCB.00472-17","article-title":"53BP1 Mediates ATR-Chk1 Signaling and Protects Replication Forks under Conditions of Replication Stress","volume":"38","author":"Her","year":"2018","journal-title":"Mol. Cell Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1016\/j.molcel.2021.06.015","article-title":"RIF1 Is Essential for 53BP1-Dependent Nonhomologous End Joining and Suppression of DNA Double-Strand Break Resection","volume":"81","author":"Chapman","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1038\/s41467-018-06407-7","article-title":"An OB-fold complex controls the repair pathways for DNA double-strand breaks","volume":"9","author":"Gao","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1042\/EBC20200007","article-title":"Repair pathway choice for double-strand breaks","volume":"64","author":"Xu","year":"2020","journal-title":"Essays Biochem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrm3719","article-title":"Double-strand break repair: 53BP1 comes into focus","volume":"15","author":"Panier","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.18632\/aging.101917","article-title":"A role of the 53BP1 protein in genome protection: Structural and functional characteristics of 53BP1-dependent DNA repair","volume":"11","author":"Bartova","year":"2019","journal-title":"Aging"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.21873\/anticanres.15292","article-title":"Detection of Endogenous DNA Double-strand Breaks in Oral Squamous Epithelial Lesions by P53-binding Protein 1","volume":"41","author":"Imaizumi","year":"2021","journal-title":"Anticancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1089\/thy.2018.0548","article-title":"A Novel Diagnostic Method for Thyroid Follicular Tumors Based on Immunofluorescence Analysis of p53-Binding Protein 1 Expression: Detection of Genomic Instability","volume":"29","author":"Otsubo","year":"2019","journal-title":"Thyroid"},{"key":"ref_133","first-page":"604","article-title":"53BP1 regulates cell cycle arrest in esophageal cancer model","volume":"23","author":"Yang","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1159\/000077512","article-title":"Possible causes of chromosome instability: Comparison of chromosomal abnormalities in cancer cell lines with mutations in BRCA1, BRCA2, CHK2 and BUB1","volume":"104","author":"Grigorova","year":"2004","journal-title":"Cytogenet. Genom. Res."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Sishc, B.J., and Davis, A.J. (2017). The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer. Cancers, 9.","DOI":"10.3390\/cancers9070081"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1155\/S1110724302204052","article-title":"Homologous Recombination and Its Role in Carcinogenesis","volume":"2","author":"Bishop","year":"2002","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1055\/s-0032-1308989","article-title":"Squamous cell carcinomas of the head and neck in Fanconi anemia: Risk, prevention, therapy, and the need for guidelines","volume":"224","author":"Scheckenbach","year":"2012","journal-title":"Klin. Padiatr."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"18198","DOI":"10.18632\/oncotarget.24797","article-title":"Fanconi anemia and homologous recombination gene variants are associated with functional DNA repair defects in vitro and poor outcome in patients with advanced head and neck squamous cell carcinoma","volume":"9","author":"Verhagen","year":"2018","journal-title":"Oncotarget"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1002\/1878-0261.13072","article-title":"FANCD2 limits acetaldehyde-induced genomic instability during DNA replication in esophageal keratinocytes","volume":"15","author":"Peake","year":"2021","journal-title":"Mol. Oncol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/annonc\/mdt384","article-title":"PARP Inhibitors for BRCA1\/2 mutation-associated and BRCA-like malignancies","volume":"25","author":"Lee","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"E1625","DOI":"10.1002\/hed.24290","article-title":"Molecular profiling of head and neck squamous cell carcinoma","volume":"38","author":"Feldman","year":"2016","journal-title":"Head Neck"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"9988","DOI":"10.1073\/pnas.0402105101","article-title":"Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity","volume":"101","author":"Bugreev","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e98162","DOI":"10.15252\/embj.201798162","article-title":"Two distinct conformational states define the interaction of human RAD51-ATP with single-stranded DNA","volume":"37","author":"Brouwer","year":"2018","journal-title":"EMBO J."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Choi, J., Kong, M., Gallagher, D.N., Li, K., Bronk, G., Cao, Y., Greene, E.C., and Haber, J.E. (2022). Repair of mismatched templates during Rad51-dependent Break-Induced Replication. PLoS Genet., 18.","DOI":"10.1101\/2022.01.30.478419"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/jcb.20232","article-title":"Xrcc3 is recruited to DNA double strand breaks early and independent of Rad51","volume":"93","author":"Forget","year":"2004","journal-title":"J. Cell Biochem."},{"key":"ref_146","first-page":"2789035","article-title":"Genetic Polymorphisms in the RAD51 Gene with a Risk of Head and Neck Cancer and Esophageal Cancer: A Meta-Analysis","volume":"2019","author":"Li","year":"2019","journal-title":"Int. J. Genom."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.yexmp.2010.08.005","article-title":"Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population","volume":"89","author":"Sliwinski","year":"2010","journal-title":"Exp. Mol. Pathol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.gene.2012.05.030","article-title":"Genetic variability of Xrcc3 and Rad51 modulates the risk of head and neck cancer","volume":"504","author":"Gresner","year":"2012","journal-title":"Gene"},{"key":"ref_149","first-page":"6412","article-title":"Association between RAD51 polymorphisms and susceptibility of head and neck cancer: A meta-analysis","volume":"8","author":"Kong","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1827676","DOI":"10.1155\/2020\/1827676","article-title":"Expression of RAD51 and Its Clinical Impact in Oral Squamous Cell Carcinoma","volume":"2020","author":"Li","year":"2020","journal-title":"Anal. Cell Pathol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1158\/1535-7163.MCT-20-0252","article-title":"Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress","volume":"20","author":"Lindemann","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"635","DOI":"10.3389\/fonc.2019.00635","article-title":"DNA-PK as an Emerging Therapeutic Target in Cancer","volume":"9","author":"Mohiuddin","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"607428","DOI":"10.3389\/fgene.2020.607428","article-title":"DNA-PKcs: A Multi-Faceted Player in DNA Damage Response","volume":"11","author":"Yue","year":"2020","journal-title":"Front. Genet."},{"key":"ref_154","first-page":"913","article-title":"Interactive competition between homologous recombination and non-homologous end joining","volume":"1","author":"Allen","year":"2003","journal-title":"Mol. Cancer Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ccell.2015.06.004","article-title":"DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis","volume":"28","author":"Goodwin","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_156","first-page":"979","article-title":"Expression and clinical significance of DNA-PKcs in nasopharyngeal carcinoma","volume":"27","author":"Yan","year":"2008","journal-title":"Ai Zheng"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.3892\/ol.2013.1196","article-title":"Expression of DNA-PKcs and BRCA1 as prognostic indicators in nasopharyngeal carcinoma following intensity-modulated radiation therapy","volume":"5","author":"Yang","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1111\/j.1349-7006.2003.tb01372.x","article-title":"Up-regulation of DNA-dependent protein kinase correlates with radiation resistance in oral squamous cell carcinoma","volume":"94","author":"Shintani","year":"2003","journal-title":"Cancer Sci."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Matsumoto, Y. (2022). Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084264"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.oraloncology.2005.12.016","article-title":"Expression of Ku80 correlates with sensitivities to radiation in cancer cell lines of the head and neck","volume":"42","author":"Chang","year":"2006","journal-title":"Oral Oncol."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Zahid, S., Seif El Dahan, M., Iehl, F., Fernandez-Varela, P., Le Du, M.H., Ropars, V., and Charbonnier, J.B. (2021). The Multifaceted Roles of Ku70\/80. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084134"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.3892\/ol.2015.3635","article-title":"Overexpression of Ku80 correlates with aggressive clinicopathological features and adverse prognosis in esophageal squamous cell carcinoma","volume":"10","author":"Wang","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1177\/2050640619856459","article-title":"Screening for head and neck second primary tumors in patients with esophageal squamous cell cancer: A systematic review and meta-analysis","volume":"7","author":"Bugter","year":"2019","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"E1909","DOI":"10.1002\/hed.24347","article-title":"Effect of beta-catenin silencing in overcoming radioresistance of head and neck cancer cells by antagonizing the effects of AMPK on Ku70\/Ku80","volume":"38","author":"Chang","year":"2016","journal-title":"Head Neck"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3892\/ol.2021.13147","article-title":"Expression of non-homologous end joining factor, Ku80, is negatively correlated with PD-L1 expression in cancer cells after X-ray irradiation","volume":"23","author":"Kumazawa","year":"2022","journal-title":"Oncol. Lett."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1093\/nar\/gky088","article-title":"Super-resolution imaging identifies PARP1 and the Ku complex acting as DNA double-strand break sensors","volume":"46","author":"Yang","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"6465","DOI":"10.1158\/1078-0432.CCR-14-0176","article-title":"Dual disruption of DNA repair and telomere maintenance for the treatment of head and neck cancer","volume":"20","author":"Lajud","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network, Weinstein, J.N., Collisson, E.A., Mills, G.B., Mills Shaw, K.R., Ozenberger, B.A., Ellrott, K., Shmulevich, I., Sander, C., and Stuart, J.M. (2013). The Cancer Genome Atlas Pan-Cancer analysis project. Nat. Genet., 45, 1113\u20131120.","DOI":"10.1038\/ng.2764"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/mc.23363","article-title":"PARP5B is required for nonhomologous end joining during tumorigenesis in vivo","volume":"61","author":"Wu","year":"2022","journal-title":"Mol. Carcinog."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s12943-019-1100-5","article-title":"MRE11-RAD50-NBS1 complex alterations and DNA damage response: Implications for cancer treatment","volume":"18","author":"Bian","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s13045-022-01360-x","article-title":"The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment","volume":"15","author":"Li","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"799","DOI":"10.3389\/fonc.2019.00799","article-title":"Misrepair in Context: TGFbeta Regulation of DNA Repair","volume":"9","author":"Liu","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_173","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_174","doi-asserted-by":"crossref","first-page":"683688","DOI":"10.3389\/fonc.2021.683688","article-title":"Dual Inhibition of PARP and the Intra-S\/G2 Cell Cycle Checkpoints Results in Highly Effective Radiosensitization of HPV(\u2212)Positive HNSCC Cells","volume":"11","author":"Hintelmann","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"81662","DOI":"10.18632\/oncotarget.20953","article-title":"Novel DNA targeted therapies for head and neck cancers: Clinical potential and biomarkers","volume":"8","author":"Glorieux","year":"2017","journal-title":"Oncotarget"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1007\/s10147-019-01586-9","article-title":"Associations between expression levels of nine core nucleotide excision repair genes in lymphocytes and risk of head and neck squamous cell carcinomas in a Chinese population","volume":"25","author":"Ren","year":"2020","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1002\/mc.22801","article-title":"Associations between expression levels of nucleotide excision repair proteins in lymphoblastoid cells and risk of squamous cell carcinoma of the head and neck","volume":"57","author":"Han","year":"2018","journal-title":"Mol. Carcinog."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1007\/s00784-018-2751-0","article-title":"ERCC1, XPF and XPA-locoregional differences and prognostic value of DNA repair protein expression in patients with head and neck squamous cell carcinoma","volume":"23","author":"Prochnow","year":"2019","journal-title":"Clin. Oral Investig."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1031944","DOI":"10.3389\/fonc.2022.1031944","article-title":"Targeting DNA damage response as a potential therapeutic strategy for head and neck squamous cell carcinoma","volume":"12","author":"Lei","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_180","first-page":"378","article-title":"Predictive biomarkers for combined chemotherapy with 5-fluorouracil and cisplatin in oro- and hypopharyngeal cancers","volume":"8","author":"Hasegawa","year":"2018","journal-title":"Mol. Clin. Oncol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/jop.12529","article-title":"DNA base excision repair proteins APE-1 and XRCC-1 are overexpressed in oral tongue squamous cell carcinoma","volume":"46","author":"Santana","year":"2017","journal-title":"J. Oral Pathol. Med."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"710694","DOI":"10.3389\/fonc.2021.710694","article-title":"The Prognostic Value of the DNA Repair Gene Signature in Head and Neck Squamous Cell Carcinoma","volume":"11","author":"Ming","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1080\/20014091074219","article-title":"Molecular mechanisms of DNA damage and repair: Progress in plants","volume":"36","author":"Tuteja","year":"2001","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1093\/carcin\/12.9.1627","article-title":"Immortalization of normal human oral keratinocytes with type 16 human papillomavirus","volume":"12","author":"Park","year":"1991","journal-title":"Carcinogenesis"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nrc798","article-title":"Papillomaviruses and cancer: From basic studies to clinical application","volume":"2","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1002\/ijc.25474","article-title":"Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways","volume":"128","author":"Smeets","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.radonc.2014.08.026","article-title":"Human papillomavirus type 16 E7 oncoprotein causes a delay in repair of DNA damage","volume":"113","author":"Park","year":"2014","journal-title":"Radiother. Oncol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"6001","DOI":"10.1158\/1078-0432.CCR-18-1346","article-title":"Subjugation of TGFbeta Signaling by Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma Shifts DNA Repair from Homologous Recombination to Alternative End Joining","volume":"24","author":"Liu","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s10555-020-09940-4","article-title":"Cyclin-dependent kinase inhibitors in head and neck cancer and glioblastoma-backbone or add-on in immune-oncology?","volume":"40","author":"Riess","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.rpor.2017.01.003","article-title":"Is immunohistochemical evaluation of p16 in oropharyngeal cancer enough to predict the HPV positivity?","volume":"22","author":"Golusinski","year":"2017","journal-title":"Rep. Pract. Oncol. Radiother."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3322\/caac.21388","article-title":"The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more \u201cpersonalized\u201d approach to cancer staging","volume":"67","author":"Amin","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/00016489.2020.1813906","article-title":"The value of p16 and HPV DNA in non-tonsillar, non-base of tongue oropharyngeal cancer","volume":"141","author":"Hammarstedt","year":"2021","journal-title":"Acta Otolaryngol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"8351","DOI":"10.7314\/APJCP.2014.15.19.8351","article-title":"Risk stratification of early stage oral tongue cancers based on HPV status and p16 immunoexpression","volume":"15","author":"Ramshankar","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"5557","DOI":"10.21873\/anticanres.15369","article-title":"Double Positivity for HPV DNA\/P16(INK4a) Does Not Influence Survival of Patients With Oral Squamous Cell Carcinoma","volume":"41","author":"Alsharif","year":"2021","journal-title":"Anticancer Res."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"3785","DOI":"10.1200\/JCO.2008.16.0812","article-title":"A synthetic lethal therapeutic approach: Poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair","volume":"26","author":"Ashworth","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"5431","DOI":"10.2174\/138161212803307608","article-title":"Synthetic lethality and PARP-inhibitors in oral and head & neck cancer","volume":"18","author":"Forster","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.oraloncology.2010.03.004","article-title":"Advances in chemotherapy for head and neck cancer","volume":"46","author":"Bhide","year":"2010","journal-title":"Oral Oncol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.oraloncology.2008.05.014","article-title":"Current concepts for the management of head and neck cancer: Chemotherapy","volume":"45","author":"Specenier","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa0912217","article-title":"Human papillomavirus and survival of patients with oropharyngeal cancer","volume":"363","author":"Ang","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.dnarep.2018.08.022","article-title":"The comings and goings of PARP-1 in response to DNA damage","volume":"71","author":"Pascal","year":"2018","journal-title":"DNA Repair"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1056\/NEJMcibr052331","article-title":"Treating cancer by targeting a weakness","volume":"353","author":"Brody","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1083\/jcb.201012132","article-title":"PARP regulates nonhomologous end joining through retention of Ku at double-strand breaks","volume":"194","author":"Couto","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1038\/s41467-019-10741-9","article-title":"Poly(ADP-ribose) polymerase-1 antagonizes DNA resection at double-strand breaks","volume":"10","author":"Caron","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1073\/pnas.1013715108","article-title":"Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells","volume":"108","author":"Patel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.1158\/0008-5472.CAN-09-4716","article-title":"Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination-defective cells","volume":"70","author":"Gottipati","year":"2010","journal-title":"Cancer Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"26995","DOI":"10.18632\/oncotarget.4863","article-title":"DNA double strand break repair defect and sensitivity to poly ADP-ribose polymerase (PARP) inhibition in human papillomavirus 16-positive head and neck squamous cell carcinoma","volume":"6","author":"Weaver","year":"2015","journal-title":"Oncotarget"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"105171","DOI":"10.1016\/j.oraloncology.2020.105171","article-title":"A phase I trial adding poly(ADP-ribose) polymerase inhibitor veliparib to induction carboplatin-paclitaxel in patients with head and neck squamous cell carcinoma: Alliance A091101","volume":"114","author":"Jelinek","year":"2021","journal-title":"Oral Oncol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1158\/1078-0432.CCR-19-0514","article-title":"PARP Inhibition Enhances Radiotherapy of SMAD4-Deficient Human Head and Neck Squamous Cell Carcinomas in Experimental Models","volume":"26","author":"Hernandez","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.ijrobp.2019.02.053","article-title":"Characterisation of Deubiquitylating Enzymes in the Cellular Response to High-LET Ionizing Radiation and Complex DNA Damage","volume":"104","author":"Carter","year":"2019","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1002\/hed.26155","article-title":"Proton and photon radiosensitization effects of niraparib, a PARP-1\/-2 inhibitor, on human head and neck cancer cells","volume":"42","author":"Wang","year":"2020","journal-title":"Head Neck"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1080\/09553002.2020.1730014","article-title":"Targeting DNA damage response in head and neck cancers through abrogation of cell cycle checkpoints","volume":"97","author":"Molkentine","year":"2021","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"TPS6105","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS6105","article-title":"A phase II study evaluating the efficacy of niraparib and dostarlimab (TSR-042) in recurrent\/metastatic head and neck squamous cell carcinoma","volume":"40","author":"Mathews","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"731798","DOI":"10.3389\/fphar.2021.731798","article-title":"PD-1\/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"705096","DOI":"10.3389\/fimmu.2021.705096","article-title":"Anti-PD-1 and Anti-PD-L1 in Head and Neck Cancer: A Network Meta-Analysis","volume":"12","author":"Botticelli","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/1878-0261.12155","article-title":"Emerging functions of the EGFR in cancer","volume":"12","author":"Sigismund","year":"2018","journal-title":"Mol. Oncol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0202-2","article-title":"Beyond EGFR inhibition: Multilateral combat strategies to stop the progression of head and neck cancer","volume":"51","author":"Byeon","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"5760","DOI":"10.1038\/s41598-022-09779-5","article-title":"DNA damage alters EGFR signaling and reprograms cellular response via Mre-11","volume":"12","author":"Volman","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"782-e70","DOI":"10.1634\/theoncologist.2017-0069","article-title":"Multicenter Phase II Study of Panitumumab in Platinum Pretreated, Advanced Head and Neck Squamous Cell Cancer","volume":"22","author":"Siano","year":"2017","journal-title":"Oncologist"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"813","DOI":"10.21037\/atm.2020.04.07","article-title":"EGFR in head and neck squamous cell carcinoma: Exploring possibilities of novel drug combinations","volume":"8","author":"Rehmani","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1667\/RR15480.1","article-title":"Combined EGFR1 and PARP1 Inhibition Enhances the Effect of Radiation in Head and Neck Squamous Cell Carcinoma Models","volume":"194","author":"Frederick","year":"2020","journal-title":"Radiat. Res."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"4949","DOI":"10.1158\/1078-0432.CCR-18-0467","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","volume":"24","author":"Karam","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Abourehab, M.A.S., Alqahtani, A.M., Youssif, B.G.M., and Gouda, A.M. (2021). Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism. Molecules, 26.","DOI":"10.3390\/molecules26216677"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fonc.2012.00031","article-title":"Radiotherapy and erlotinib combined: Review of the preclinical and clinical evidence","volume":"2","author":"Mehta","year":"2012","journal-title":"Front. Oncol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1158\/1078-0432.CCR-21-3025","article-title":"Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (ALPHA Study): A Phase II Study with Biomarker Analysis","volume":"28","author":"Kao","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ctro.2020.11.003","article-title":"Dacomitinib and gedatolisib in combination with fractionated radiation in head and neck cancer","volume":"26","author":"Wilson","year":"2021","journal-title":"Clin. Transl. Radiat. Oncol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1158\/1541-7786.MCR-18-0860","article-title":"Multiple Defects Sensitize p53-Deficient Head and Neck Cancer Cells to the WEE1 Kinase Inhibition","volume":"17","author":"Diab","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1158\/1078-0432.CCR-17-3796","article-title":"A Phase I Clinical Trial of AZD1775 in Combination with Neoadjuvant Weekly Docetaxel and Cisplatin before Definitive Therapy in Head and Neck Squamous Cell Carcinoma","volume":"24","author":"Mendez","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.1242\/jcs.00908","article-title":"Wee1-dependent mechanisms required for coordination of cell growth and cell division","volume":"116","author":"Kellogg","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Esposito, F., Giuffrida, R., Raciti, G., Puglisi, C., and Forte, S. (2021). Wee1 Kinase: A Potential Target to Overcome Tumor Resistance to Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910689"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.devcel.2016.11.017","article-title":"A Mechanism for Controlled Breakage of Under-replicated Chromosomes during Mitosis","volume":"39","author":"Duda","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_231","first-page":"1913","article-title":"CDK inhibitors in cancer therapy, an overview of recent development","volume":"11","author":"Zhang","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1158\/1535-7163.MCT-19-0695","article-title":"Preclinical Activity of Ribociclib in Squamous Cell Carcinoma of the Head and Neck","volume":"19","author":"Schmitz","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3389\/fonc.2019.00155","article-title":"Phase 1 Study Evaluating the Association of the Cyclin-Dependent Kinase 4\/6 Inhibitor Ribociclib and Cetuximab in Recurrent\/Metastatic p16-Negative Squamous Cell Carcinoma of the Head and Neck","volume":"9","author":"Seront","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/S1470-2045(19)30405-X","article-title":"Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papillomavirus-unrelated head and neck cancer: A multicentre, multigroup, phase 2 trial","volume":"20","author":"Adkins","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.3389\/fgene.2020.01036","article-title":"Combining PARP and DNA-PK Inhibitors With Irradiation Inhibits HPV(\u2212)Negative Head and Neck Cancer Squamous Carcinoma Growth","volume":"11","author":"Zeng","year":"2020","journal-title":"Front. Genet."},{"key":"ref_236","doi-asserted-by":"crossref","unstructured":"Faulhaber, E.M., Jost, T., Symank, J., Scheper, J., Burkel, F., Fietkau, R., Hecht, M., and Distel, L.V. (2021). Kinase Inhibitors of DNA-PK, ATM and ATR in Combination with Ionizing Radiation Can Increase Tumor Cell Death in HNSCC Cells While Sparing Normal Tissue Cells. Genes, 12.","DOI":"10.3390\/genes12060925"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/mc.23384","article-title":"Pharmacologic inhibition of ataxia telangiectasia and Rad3-related (ATR) in the treatment of head and neck squamous cell carcinoma","volume":"61","author":"Karukonda","year":"2022","journal-title":"Mol. Carcinog."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.oraloncology.2019.05.028","article-title":"ATR inhibition sensitizes HPV(\u2212) and HPV(+) head and neck squamous cell carcinoma to cisplatin","volume":"95","author":"Leonard","year":"2019","journal-title":"Oral Oncol."},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Dok, R., Glorieux, M., Bamps, M., and Nuyts, S. (2021). Effect of ATR Inhibition in RT Response of HPV(\u2212)Negative and HPV(\u2212)Positive Head and Neck Cancers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041504"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"E45","DOI":"10.1016\/j.ijrobp.2021.12.105","article-title":"Evaluating the Therapeutic Potential of a Small Molecule ATR Inhibitor Combined with Radiotherapy for Head and Neck Squamous Cell Carcinoma","volume":"112","author":"Odhiambo","year":"2022","journal-title":"Radiat. Oncol. Biol. Phys."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"e004306","DOI":"10.1136\/jitc-2021-004306","article-title":"Harnessing radiotherapy-induced NK-cell activity by combining DNA damage-response inhibition and immune checkpoint blockade","volume":"10","author":"Patin","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"TPS6108","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS6108","article-title":"Phase I trial of the ATR inhibitor BAY 1895344 combined with stereotactic body radiation therapy and pembrolizumab for recurrent head and neck squamous cell carcinoma","volume":"40","author":"Mowery","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1667\/RR13515.1","article-title":"DNA damage response genes and the development of cancer metastasis","volume":"181","author":"Broustas","year":"2014","journal-title":"Radiat. 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