{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:32:36Z","timestamp":1777984356039,"version":"3.51.4"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008967","name":"Philipps-Universit\u00e4t Marburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008967","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Radiat Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Radiation-induced senescence strongly contributes to therapy resistance in HPV-negative head and neck squamous cell carcinoma (HNSCC). In particular, the NF-\n                      <jats:inline-formula>\n                        <jats:tex-math>$${\\rm{\\kappa }}$$<\/jats:tex-math>\n                      <\/jats:inline-formula>\n                      B-dependent arm of the senescence-associated secretory phenotype (SASP) activates signaling pathways that are tightly associated with, and promote, resistance to irradiation. In addition to the SASP, another hallmark of senescence is the upregulation of anti-apoptotic proteins. The BH3-only mimetic ABT-263 has been shown to effectively eliminate senescent cells. In this study, we employed ABT-263 to overcome the therapy-induced resistance in HNSCC cells and uncovered a link to chemokine signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The HNSCC cell lines Cal33 and UPCI:SCC040 were treated with a combination of ABT-263 and photon irradiation, followed by functional and mechanistic assays assessing viability, apoptosis, senescence, secreted proteins, clonogenic survival, and DNA repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Functionally, ABT-263 induced apoptosis via impeding Bcl-xL and activating Bax. Senescence levels were reduced after irradiation. Mechanistically, we observed cell-line- and protein-specific changes in the SASP, including a striking difference in CXCR2 receptor expression. Cal33 cells exhibited strong downregulation of CXCR2 and were radiosensitized by ABT-263, as indicated by reduced viability and clonogenic survival. In contrast, CXCR2 expression was induced in UPCI:SCC040 cells following treatment; although viability was diminished, clonogenic survival remained unaffected. Notably, radiosensitization in UPCI:SCC040 cells could be achieved through concomitant inhibition of CXCR2. Furthermore, the radiosensitizing effect was not attributable to increased DNA damage, as evidenced by\n                      <jats:inline-formula>\n                        <jats:tex-math>$$\\gamma $$<\/jats:tex-math>\n                      <\/jats:inline-formula>\n                      H2AX\/53BP1 co-localization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings highlight a central role for CXCR2-mediated signaling in the development of radioresistance in HPV-negative HNSCC cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13014-026-02798-w","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T09:54:10Z","timestamp":1770890050000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CXCR2 affects sensitization of radioresistant HPV-negative head and neck squamous cell carcinoma cells by ABT-263"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2827-7932","authenticated-orcid":false,"given":"Sibylla","family":"Kohl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9873-0432","authenticated-orcid":false,"given":"Mareike","family":"Schaper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Arteaga","family":"Lajar\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8525-5429","authenticated-orcid":false,"given":"Florentine S. B.","family":"Subtil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7444-9033","authenticated-orcid":false,"given":"Rita","family":"Engenhart-Cabillic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekkehard","family":"Dikomey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8463-514X","authenticated-orcid":false,"given":"Sebastian","family":"Adeberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8118-3977","authenticated-orcid":false,"given":"Ulrike","family":"Thei\u00df","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"issue":"11","key":"2798_CR1","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1016\/j.annonc.2020.07.011","volume":"31","author":"JP Machiels","year":"2020","unstructured":"Machiels JP, Rene Leemans C, Golusinski W, Grau C, Licitra L, Gregoire V, et al. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(11):1462\u201375. https:\/\/doi.org\/10.1016\/j.annonc.2020.07.011.","journal-title":"Ann Oncol"},{"issue":"5","key":"2798_CR2","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1016\/j.ijrobp.2012.05.008","volume":"84","author":"JS Cooper","year":"2012","unstructured":"Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, et al. Long-term follow-up of the RTOG 9501\/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012;84(5):1198\u2013205. https:\/\/doi.org\/10.1016\/j.ijrobp.2012.05.008.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"2798_CR3","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s13014-018-1067-1","volume":"13","author":"C Maihoefer","year":"2018","unstructured":"Maihoefer C, Schuttrumpf L, Macht C, Pflugradt U, Hess J, Schneider L, et al. Postoperative (chemo) radiation in patients with squamous cell cancers of the head and neck - clinical results from the cohort of the clinical cooperation group \u201cpersonalized radiotherapy in head and neck Cancer\u201d. Radiat Oncol. 2018;13(1):123. https:\/\/doi.org\/10.1186\/s13014-018-1067-1.","journal-title":"Radiat Oncol"},{"issue":"Suppl, 10","key":"2798_CR4","doi-asserted-by":"publisher","first-page":"x173","DOI":"10.1093\/annonc\/mds299","volume":"23","author":"BJ Braakhuis","year":"2012","unstructured":"Braakhuis BJ, Brakenhoff RH, Leemans CR. Treatment choice for locally advanced head and neck cancers on the basis of risk factors: biological risk factors. Ann Oncol. 2012;23(Suppl, 10):x173\u20137. https:\/\/doi.org\/10.1093\/annonc\/mds299.","journal-title":"Ann Oncol"},{"issue":"1","key":"2798_CR5","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/s42003-021-02257-0","volume":"4","author":"K Santos-de-Frutos","year":"2021","unstructured":"Santos-de-Frutos K, Djouder N. When dormancy fuels tumour relapse. Commun Biol. 2021;4(1):747. https:\/\/doi.org\/10.1038\/s42003-021-02257-0.","journal-title":"Commun Biol"},{"issue":"7","key":"2798_CR6","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1158\/2159-8290.CD-19-0015","volume":"9","author":"S Yuan","year":"2019","unstructured":"Yuan S, Norgard RJ, Stanger BZ. Cellular plasticity in Cancer. Cancer Discov. 2019;9(7):837\u201351. https:\/\/doi.org\/10.1158\/2159-8290.CD-19-0015.","journal-title":"Cancer Discov"},{"issue":"1","key":"2798_CR7","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s13014-022-02171-7","volume":"17","author":"H Chen","year":"2022","unstructured":"Chen H, Han Z, Luo Q, Wang Y, Li Q, Zhou L, et al. Radiotherapy modulates tumor cell fate decisions: a review. Radiat Oncol. 2022;17(1):196. https:\/\/doi.org\/10.1186\/s13014-022-02171-7.","journal-title":"Radiat Oncol"},{"issue":"1","key":"2798_CR8","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13014-022-02184-2","volume":"18","author":"JH Kim","year":"2023","unstructured":"Kim JH, Brown SL, Gordon MN. Radiation-induced senescence: therapeutic opportunities. Radiat Oncol. 2023;18(1):10. https:\/\/doi.org\/10.1186\/s13014-022-02184-2.","journal-title":"Radiat Oncol"},{"issue":"4","key":"2798_CR9","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1172\/JCI95148","volume":"128","author":"N Herranz","year":"2018","unstructured":"Herranz N, Gil J. Mechanisms and functions of cellular senescence. J Clin Invest. 2018;128(4):1238\u201346. https:\/\/doi.org\/10.1172\/JCI95148.","journal-title":"J Clin Invest"},{"issue":"1","key":"2798_CR10","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/2041-9414-2-7","volume":"2","author":"RJ Sabin","year":"2011","unstructured":"Sabin RJ, Anderson RM. Cellular senescence - its role in cancer and the response to ionizing radiation. Genome Integr. 2011;2(1):7. https:\/\/doi.org\/10.1186\/2041-9414-2-7.","journal-title":"Genome Integr"},{"key":"2798_CR11","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","volume":"5","author":"JP Coppe","year":"2010","unstructured":"Coppe JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010;5:99\u2013118. https:\/\/doi.org\/10.1146\/annurev-pathol-121808-102144.","journal-title":"Annu Rev Pathol"},{"issue":"10","key":"2798_CR12","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1038\/s41416-018-0066-1","volume":"118","author":"JM Gonzalez-Meljem","year":"2018","unstructured":"Gonzalez-Meljem JM, Apps JR, Fraser HC, Martinez-Barbera JP. Paracrine roles of cellular senescence in promoting tumourigenesis. Br J Cancer. 2018;118(10):1283\u201388. https:\/\/doi.org\/10.1038\/s41416-018-0066-1.","journal-title":"Br J Cancer"},{"key":"2798_CR13","doi-asserted-by":"publisher","first-page":"878675","DOI":"10.3389\/fonc.2022.878675","volume":"12","author":"DK Tiwari","year":"2022","unstructured":"Tiwari DK, Hannen R, Unger K, Kohl S, Hess J, Lauber K, et al. IL1 pathway in HPV-Negative HNSCC cells is an indicator of radioresistance after photon and carbon ion irradiation without functional Involvement. Front Oncol. 2022;12:878675. https:\/\/doi.org\/10.3389\/fonc.2022.878675.","journal-title":"Front Oncol"},{"issue":"12","key":"2798_CR14","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1038\/s41419-021-04454-5","volume":"12","author":"U Schoetz","year":"2021","unstructured":"Schoetz U, Klein D, Hess J, Shnayien S, Spoerl S, Orth M, et al. Early senescence and production of senescence-associated cytokines are major determinants of radioresistance in head-and-neck squamous cell carcinoma. Cell Death Dis. 2021;12(12):1162. https:\/\/doi.org\/10.1038\/s41419-021-04454-5.","journal-title":"Cell Death Dis"},{"key":"2798_CR15","doi-asserted-by":"publisher","unstructured":"Crist M, Yaniv B, Palackdharry S, Lehn MA, Medvedovic M, Stone T, et al. Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition. J Immunother Cancer. 2022;10(11). https:\/\/doi.org\/10.1136\/jitc-2022-005632.","DOI":"10.1136\/jitc-2022-005632"},{"issue":"5","key":"2798_CR16","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1111\/febs.16350","volume":"290","author":"L Zhang","year":"2023","unstructured":"Zhang L, Pitcher LE, Prahalad V, Niedernhofer LJ, Robbins PD. Targeting cellular senescence with senotherapeutics: senolytics and senomorphics. FEBS J. 2023;290(5):1362\u201383. https:\/\/doi.org\/10.1111\/febs.16350.","journal-title":"FEBS J"},{"issue":"2","key":"2798_CR17","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1002\/cncr.32539","volume":"126","author":"S Gulati","year":"2020","unstructured":"Gulati S, Desai J, Palackdharry SM, Morris JC, Zhu Z, Jandarov R, et al. Phase 1 dose-finding study of metformin in combination with concurrent cisplatin and radiotherapy in patients with locally advanced head and neck squamous cell cancer. Cancer. 2020;126(2):354\u201362. https:\/\/doi.org\/10.1002\/cncr.32539.","journal-title":"Cancer"},{"key":"2798_CR18","doi-asserted-by":"publisher","first-page":"106536","DOI":"10.1016\/j.oraloncology.2023.106536","volume":"145","author":"JO Kemnade","year":"2023","unstructured":"Kemnade JO, Florez M, Sabichi A, Zhang J, Jhaveri P, Chen G, et al. Phase I\/II trial of metformin as a chemo-radiosensitizer in a head and neck cancer patient population. Oral Oncol. 2023;145:106536. https:\/\/doi.org\/10.1016\/j.oraloncology.2023.106536.","journal-title":"Oral Oncol"},{"issue":"8","key":"2798_CR19","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1038\/s41591-022-01923-y","volume":"28","author":"S Chaib","year":"2022","unstructured":"Chaib S, Tchkonia T, Kirkland JL. Cellular senescence and senolytics: the path to the clinic. Nat Med. 2022;28(8):1556\u201368. https:\/\/doi.org\/10.1038\/s41591-022-01923-y.","journal-title":"Nat Med"},{"issue":"11","key":"2798_CR20","first-page":"2284","volume":"55","author":"E Wang","year":"1995","unstructured":"Wang E. Senescent human fibroblasts resist programmed cell death, and failure to suppress bcl2 is involved. Cancer Res. 1995;55(11):2284\u201392.","journal-title":"Cancer Res"},{"issue":"9","key":"2798_CR21","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1038\/sj.onc.1210220","volume":"26","author":"JM Adams","year":"2007","unstructured":"Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26(9):1324\u201337. https:\/\/doi.org\/10.1038\/sj.onc.1210220.","journal-title":"Oncogene"},{"key":"2798_CR22","doi-asserted-by":"publisher","first-page":"564108","DOI":"10.3389\/fphar.2020.564108","volume":"11","author":"NN Mohamad Anuar","year":"2020","unstructured":"Mohamad Anuar NN, Nor Hisam NS, Liew SL, Ugusman A. Clinical review: Navitoclax as a pro-apoptotic and anti-fibrotic Agent. Front Pharmacol. 2020;11:564108. https:\/\/doi.org\/10.3389\/fphar.2020.564108.","journal-title":"Front Pharmacol"},{"key":"2798_CR23","doi-asserted-by":"publisher","first-page":"105979","DOI":"10.1016\/j.oraloncology.2022.105979","volume":"132","author":"G Melo","year":"2022","unstructured":"Melo G, Silva CAB, Hague A, Parkinson EK, Rivero ERC. Anticancer effects of putative and validated BH3-mimetic drugs in head and neck squamous cell carcinomas: an overview of current knowledge. Oral Oncol. 2022;132:105979. https:\/\/doi.org\/10.1016\/j.oraloncology.2022.105979.","journal-title":"Oral Oncol"},{"issue":"10","key":"2798_CR24","doi-asserted-by":"publisher","first-page":"2504","DOI":"10.1002\/1878-0261.12761","volume":"14","author":"T Saleh","year":"2020","unstructured":"Saleh T, Carpenter VJ, Tyutyunyk-Massey L, Murray G, Leverson JD, Souers AJ, et al. Clearance of therapy-induced senescent tumor cells by the senolytic ABT-263 via interference with BCL-X(L) -BAX interaction. Mol Oncol. 2020;14(10):2504\u201319. https:\/\/doi.org\/10.1002\/1878-0261.12761.","journal-title":"Mol Oncol"},{"issue":"2","key":"2798_CR25","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.ijrobp.2017.02.216","volume":"99","author":"J Pan","year":"2017","unstructured":"Pan J, Li D, Xu Y, Zhang J, Wang Y, Chen M, et al. Inhibition of Bcl-2\/xl with ABT-263 selectively kills senescent type II pneumocytes and reverses persistent pulmonary fibrosis induced by ionizing radiation in mice. Int J Radiat Oncol Biol Phys. 2017;99(2):353\u201361. https:\/\/doi.org\/10.1016\/j.ijrobp.2017.02.216.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"6","key":"2798_CR26","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1007\/s12094-022-03070-9","volume":"25","author":"I Ploumaki","year":"2023","unstructured":"Ploumaki I, Triantafyllou E, Koumprentziotis IA, Karampinos K, Drougkas K, Karavolias I, et al. Bcl-2 pathway inhibition in solid tumors: a review of clinical trials. Clin Transl Oncol. 2023;25(6):1554\u201378. https:\/\/doi.org\/10.1007\/s12094-022-03070-9.","journal-title":"Clin Transl Oncol"},{"issue":"12","key":"2798_CR27","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1038\/nprot.2009.191","volume":"4","author":"F Debacq-Chainiaux","year":"2009","unstructured":"Debacq-Chainiaux F, Erusalimsky JD, Campisi J, Toussaint O. Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat Protoc. 2009;4(12):1798\u2013806. https:\/\/doi.org\/10.1038\/nprot.2009.191.","journal-title":"Nat Protoc"},{"key":"2798_CR28","doi-asserted-by":"publisher","unstructured":"Subtil FSB, Grobner C, Recknagel N, Parplys AC, Kohl S, Arenz A, et al. Dual PI3K\/mTOR inhibitor NVP-BEZ235 leads to a synergistic enhancement of cisplatin and radiation in both HPV-negative and -positive HNSCC cell lines. Cancers (Basel). 2022;14(13). https:\/\/doi.org\/10.3390\/cancers14133160.","DOI":"10.3390\/cancers14133160"},{"key":"2798_CR29","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.radonc.2020.07.032","volume":"151","author":"S Lerch","year":"2020","unstructured":"Lerch S, Berthold S, Ziemann F, Dreffke K, Subtil FSB, Senger Y, et al. HPV-positive HNSCC cell lines show strongly enhanced radiosensitivity after photon but not after carbon ion irradiation. Radiother Oncol. 2020;151:134\u201340. https:\/\/doi.org\/10.1016\/j.radonc.2020.07.032.","journal-title":"Radiother Oncol"},{"key":"2798_CR30","doi-asserted-by":"publisher","first-page":"100110","DOI":"10.1016\/j.crphar.2022.100110","volume":"3","author":"D Duarte","year":"2022","unstructured":"Duarte D, Vale N. Evaluation of synergism in drug combinations and reference models for future orientations in oncology. Curr Res Pharmacol Drug Discov. 2022;3:100110. https:\/\/doi.org\/10.1016\/j.crphar.2022.100110.","journal-title":"Curr Res Pharmacol Drug Discov"},{"key":"2798_CR31","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.canlet.2016.11.014","volume":"386","author":"J Hess","year":"2017","unstructured":"Hess J, Unger K, Orth M, Schotz U, Schuttrumpf L, Zangen V, et al. Genomic amplification of fanconi anemia complementation group a (FancA) in head and neck squamous cell carcinoma (HNSCC): cellular mechanisms of radioresistance and clinical relevance. Cancer Lett. 2017;386:87\u201399. https:\/\/doi.org\/10.1016\/j.canlet.2016.11.014.","journal-title":"Cancer Lett"},{"key":"2798_CR32","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13014-016-0672-0","volume":"11","author":"A Michna","year":"2016","unstructured":"Michna A, Schotz U, Selmansberger M, Zitzelsberger H, Lauber K, Unger K, et al. Transcriptomic analyses of the radiation response in head and neck squamous cell carcinoma subclones with different radiation sensitivity: time-course gene expression profiles and gene association networks. Radiat Oncol. 2016;11:94. https:\/\/doi.org\/10.1186\/s13014-016-0672-0.","journal-title":"Radiat Oncol"},{"issue":"12","key":"2798_CR33","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1038\/sj.emboj.7600675","volume":"24","author":"MG Annis","year":"2005","unstructured":"Annis MG, Soucie EL, Dlugosz PJ, Cruz-Aguado JA, Penn LZ, Leber B, et al. Bax forms multispanning monomers that oligomerize to permeabilize membranes during apoptosis. Embo J. 2005;24(12):2096\u2013103. https:\/\/doi.org\/10.1038\/sj.emboj.7600675.","journal-title":"Embo J"},{"issue":"11","key":"2798_CR34","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1091\/mbc.E11-10-0884","volume":"23","author":"A Freund","year":"2012","unstructured":"Freund A, Laberge RM, Demaria M, Campisi J. Lamin B1 loss is a senescence-associated biomarker. Mol Biol Cell. 2012;23(11):2066\u201375. https:\/\/doi.org\/10.1091\/mbc.E11-10-0884.","journal-title":"Mol Biol Cell"},{"issue":"1","key":"2798_CR35","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41420-020-00327-6","volume":"6","author":"L Lindenboim","year":"2020","unstructured":"Lindenboim L, Grozki D, Amsalem-Zafran AR, Pena-Blanco A, Gundersen GG, Borner C, et al. Apoptotic stress induces Bax-dependent, caspase-independent redistribution of LINC complex nesprins. Cell Death Discov. 2020;6(1):90. https:\/\/doi.org\/10.1038\/s41420-020-00327-6.","journal-title":"Cell Death Discov"},{"issue":"9","key":"2798_CR36","doi-asserted-by":"publisher","first-page":"3421","DOI":"10.1158\/0008-5472.CAN-07-5836","volume":"68","author":"C Tse","year":"2008","unstructured":"Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008;68(9):3421\u201328. https:\/\/doi.org\/10.1158\/0008-5472.CAN-07-5836.","journal-title":"Cancer Res"},{"issue":"8","key":"2798_CR37","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1002\/hed.20059","volume":"26","author":"H Sharma","year":"2004","unstructured":"Sharma H, Sen S, Mathur M, Bahadur S, Singh N. Combined evaluation of expression of telomerase, survivin, and anti-apoptotic Bcl-2 family members in relation to loss of differentiation and apoptosis in human head and neck cancers. Head Neck. 2004;26(8):733\u201340. https:\/\/doi.org\/10.1002\/hed.20059.","journal-title":"Head Neck"},{"issue":"4","key":"2798_CR38","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1097\/00005537-200204000-00009","volume":"112","author":"DK Trask","year":"2002","unstructured":"Trask DK, Wolf GT, Bradford CR, Fisher SG, Devaney K, Johnson M, et al. Expression of Bcl-2 family proteins in advanced laryngeal squamous cell carcinoma: correlation with response to chemotherapy and organ preservation. Laryngoscope. 2002;112(4):638\u201344. https:\/\/doi.org\/10.1097\/00005537-200204000-00009.","journal-title":"Laryngoscope"},{"issue":"7","key":"2798_CR39","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/s41419-021-03971-7","volume":"12","author":"V Ritter","year":"2021","unstructured":"Ritter V, Krautter F, Klein D, Jendrossek V, Rudner J. Bcl-2\/Bcl-xL inhibitor ABT-263 overcomes hypoxia-driven radioresistence and improves radiotherapy. Cell Death Dis. 2021;12(7):694. https:\/\/doi.org\/10.1038\/s41419-021-03971-7.","journal-title":"Cell Death Dis"},{"issue":"4","key":"2798_CR40","doi-asserted-by":"publisher","first-page":"494","DOI":"10.18632\/oncotarget.26563","volume":"10","author":"TJ Ow","year":"2019","unstructured":"Ow TJ, Fulcher CD, Thomas C, Broin PO, Lopez A, Reyna DE, et al. Optimal targeting of BCL-family proteins in head and neck squamous cell carcinoma requires inhibition of both BCL-xL and MCL-1. Oncotarget. 2019;10(4):494\u2013510. https:\/\/doi.org\/10.18632\/oncotarget.26563.","journal-title":"Oncotarget"},{"issue":"2","key":"2798_CR41","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1042\/BCJ20160459","volume":"474","author":"E Lukasova","year":"2017","unstructured":"Lukasova E, Kovar A, Bac A, Falk M, Kozubek S. Loss of lamin B receptor is necessary to induce cellular senescence. Biochem J. 2017;474(2):281\u2013300. https:\/\/doi.org\/10.1042\/BCJ20160459.","journal-title":"Biochem J"},{"key":"2798_CR42","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s13014-015-0474-9","volume":"10","author":"SF Zerp","year":"2015","unstructured":"Zerp SF, Stoter TR, Hoebers FJ, van den Brekel MW, Dubbelman R, Kuipers GK, et al. Targeting anti-apoptotic Bcl-2 by AT-101 to increase radiation efficacy: data from in vitro and clinical pharmacokinetic studies in head and neck cancer. Radiat Oncol. 2015;10:158. https:\/\/doi.org\/10.1186\/s13014-015-0474-9.","journal-title":"Radiat Oncol"},{"issue":"1","key":"2798_CR43","doi-asserted-by":"publisher","first-page":"14755","DOI":"10.1038\/s41598-021-94259-5","volume":"11","author":"K Tuomainen","year":"2021","unstructured":"Tuomainen K, Hyytiainen A, Al-Samadi A, Ianevski P, Ianevski A, Potdar S, et al. High-throughput compound screening identifies navitoclax combined with irradiation as a candidate therapy for HPV-negative head and neck squamous cell carcinoma. Sci Rep. 2021;11(1):14755. https:\/\/doi.org\/10.1038\/s41598-021-94259-5.","journal-title":"Sci Rep"},{"key":"2798_CR44","doi-asserted-by":"publisher","unstructured":"Korbecki J, Kupnicka P, Chlubek M, Goracy J, Gutowska I, Baranowska-Bosiacka I. CXCR2 receptor: regulation of expression, signal transduction, and Involvement in Cancer. Int J Mol Sci. 2022;23(4). https:\/\/doi.org\/10.3390\/ijms23042168.","DOI":"10.3390\/ijms23042168"},{"issue":"11","key":"2798_CR45","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1007\/s00210-019-01671-w","volume":"392","author":"T Ma","year":"2019","unstructured":"Ma T, Zhao Z, Wang Z, Wang C, Zhang L. MiR-940 inhibits migration and invasion of tongue squamous cell carcinoma via regulatingCXCR2\/NF-kappaB system-mediated epithelial-mesenchymal transition. Naunyn Schmiedebergs Arch Pharmacol. 2019;392(11):1359\u201369. https:\/\/doi.org\/10.1007\/s00210-019-01671-w.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"1","key":"2798_CR46","doi-asserted-by":"publisher","first-page":"4107","DOI":"10.1038\/s41467-023-39799-2","volume":"14","author":"N Ishimoto","year":"2023","unstructured":"Ishimoto N, Park JH, Kawakami K, Tajiri M, Mizutani K, Akashi S, et al. Structural basis of CXC chemokine receptor 1 ligand binding and activation. Nat Commun. 2023;14(1):4107. https:\/\/doi.org\/10.1038\/s41467-023-39799-2.","journal-title":"Nat Commun"},{"issue":"1","key":"2798_CR47","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1186\/s13046-024-03240-3","volume":"43","author":"LA Horn","year":"2024","unstructured":"Horn LA, Lind H, Fousek K, Qin H, Rajabian N, Angstadt S, et al. Inhibition of the chemokine receptors CXCR1 and CXCR2 synergizes with docetaxel for effective tumor control and remodeling of the immune microenvironment of HPV-negative head and neck cancer models. J Exp Clin Cancer Res. 2024;43(1):318. https:\/\/doi.org\/10.1186\/s13046-024-03240-3.","journal-title":"J Exp Clin Cancer Res"},{"key":"2798_CR48","doi-asserted-by":"publisher","unstructured":"Bugia L, Affolter A, Kern J, Sohn E, Jungbauer F, Fleckenstein J, et al. Irradiation\u2011induced cellular senescence is linked to pro\u2011survival signaling and checkpoint regulation in a 2D and 3D model for head and neck cancer. Oncol Rep. 2025;54(5). https:\/\/doi.org\/10.3892\/or.2025.8984.","DOI":"10.3892\/or.2025.8984"},{"issue":"1","key":"2798_CR49","doi-asserted-by":"publisher","first-page":"71","DOI":"10.18632\/oncotarget.2698","volume":"6","author":"V Desiderio","year":"2015","unstructured":"Desiderio V, Papagerakis P, Tirino V, Zheng L, Matossian M, Prince ME, et al. Increased fucosylation has a pivotal role in invasive and metastatic properties of head and neck cancer stem cells. Oncotarget. 2015;6(1):71\u201384. https:\/\/doi.org\/10.18632\/oncotarget.2698.","journal-title":"Oncotarget"},{"issue":"1","key":"2798_CR50","doi-asserted-by":"publisher","first-page":"8845","DOI":"10.1038\/s41467-024-53015-9","volume":"15","author":"P Bergeron","year":"2024","unstructured":"Bergeron P, Dos Santos M, Sitterle L, Tarlet G, Lavigne J, Liu W, et al. Non-homogenous intratumor ionizing radiation doses synergize with PD1 and CXCR2 blockade. Nat Commun. 2024;15(1):8845. https:\/\/doi.org\/10.1038\/s41467-024-53015-9.","journal-title":"Nat Commun"},{"issue":"1","key":"2798_CR51","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s13014-021-01807-4","volume":"16","author":"L Cruz-Garcia","year":"2021","unstructured":"Cruz-Garcia L, Badie C, Anbalagan S, Moquet J, Gothard L, O\u2019Brien G, et al. An ionising radiation-induced specific transcriptional signature of inflammation-associated genes in whole blood from radiotherapy patients: a pilot study. Radiat Oncol. 2021;16(1):83. https:\/\/doi.org\/10.1186\/s13014-021-01807-4.","journal-title":"Radiat Oncol"},{"key":"2798_CR52","doi-asserted-by":"publisher","unstructured":"Sato K, Iwasaki S, Yoshino H. Effects and related mechanisms of the senolytic agent ABT-263 on the survival of irradiated A549 and Ca9-22 Cancer cells. Int J Mol Sci. 2021;22(24). https:\/\/doi.org\/10.3390\/ijms222413233.","DOI":"10.3390\/ijms222413233"},{"key":"2798_CR53","doi-asserted-by":"publisher","first-page":"116719","DOI":"10.1016\/j.biopha.2024.116719","volume":"175","author":"K Korelin","year":"2024","unstructured":"Korelin K, Oostveen M, Wahbi W, Ianevski F, Cavalcante B, Turunen L, et al. Evaluation of BH3 mimetics as a combination therapy with irradiation in head and neck squamous cell carcinoma. Biomed Pharmacother. 2024;175:116719. https:\/\/doi.org\/10.1016\/j.biopha.2024.116719.","journal-title":"Biomed Pharmacother"},{"issue":"9","key":"2798_CR54","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1111\/jop.12189","volume":"43","author":"Y Qian","year":"2014","unstructured":"Qian Y, Wang Y, Li DS, Zhu YX, Lu ZW, Ji QH, et al. The chemokine receptor-CXCR2 plays a critical role in the invasion and metastases of oral squamous cell carcinoma in vitro and in vivo. J Oral Pathol Med. 2014;43(9):658\u201366. https:\/\/doi.org\/10.1111\/jop.12189.","journal-title":"J Oral Pathol Med"},{"issue":"4","key":"2798_CR55","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1007\/s12094-023-03364-6","volume":"26","author":"K Ostrowska","year":"2024","unstructured":"Ostrowska K, Niewinski P, Piotrowski I, Ostapowicz J, Koczot S, Suchorska WM, et al. Senescence in head and neck squamous cell carcinoma: relationship between senescence-associated secretory phenotype (SASP) mRNA expression level and clinicopathological features. Clin Transl Oncol. 2024;26(4):1022\u201332. https:\/\/doi.org\/10.1007\/s12094-023-03364-6.","journal-title":"Clin Transl Oncol"},{"issue":"9","key":"2798_CR56","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1158\/1535-7163.MCT-23-0738","volume":"23","author":"MK Lee","year":"2024","unstructured":"Lee MK, Woo SR, Noh JK, Min S, Kong M, Lee YC, et al. Prognostic significance of SASP-Related gene signature of radiation therapy in head and neck squamous cell carcinoma. Mol Cancer Ther. 2024;23(9):1348\u201359. https:\/\/doi.org\/10.1158\/1535-7163.MCT-23-0738.","journal-title":"Mol Cancer Ther"}],"container-title":["Radiation Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13014-026-02798-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-026-02798-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-026-02798-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T13:59:04Z","timestamp":1771509544000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13014-026-02798-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,12]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2798"],"URL":"https:\/\/doi.org\/10.1186\/s13014-026-02798-w","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7956226\/v1","asserted-by":"object"}]},"ISSN":["1748-717X"],"issn-type":[{"value":"1748-717X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,12]]},"assertion":[{"value":"27 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"This manuscript has not been published elsewhere and is not under consideration by any other journal. All authors approved the manuscript and agree with its submission.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no potential conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"33"}}