{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:49:05Z","timestamp":1792090145515,"version":"4.4.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurooncol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Large-conductance Ca\n                      <jats:sup>2 +<\/jats:sup>\n                      -activated potassium (BK\n                      <jats:sub>Ca<\/jats:sub>\n                      ) channels have been implicated in glioblastoma progression and oxidative stress; however, their contribution to the cellular response to ionizing radiation remains poorly understood. Potassium channels represent attractive therapeutic targets because their activity can be modulated pharmacologically using selective inhibitors or genetically by gene silencing (siRNA) or gene knockout (CRISPR\/Cas9). Here, we investigated whether genetic inhibition of BK\n                      <jats:sub>Ca<\/jats:sub>\n                      modulates the DNA damage response of human glioblastoma cells following electron ultra-high dose rate (UHDR) irradiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Human U87MG glioblastoma cells and BK\n                      <jats:sub>Ca<\/jats:sub>\n                      -knockout cells (U87MG \u0394\u03b1BK\n                      <jats:sub>Ca<\/jats:sub>\n                      ) were exposed to an electron UHDR\u20139\u2009MeV beam with an average dose rate of 150\u2009Gy\/s. Clonogenic survival, reactive oxygen species levels, cell-cycle distribution, apoptosis, DNA-DSBs, DNA repair, and expression of selected genes encoding DDR pathways were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BK\n                      <jats:sub>Ca<\/jats:sub>\n                      deletion did not significantly alter clonogenic survival following UHDR irradiation. Cells lacking the BK\n                      <jats:sub>Ca<\/jats:sub>\n                      channel exhibited elevated ROS levels, altered cell cycle distribution with G0\/G1 accumulation, and enhanced apoptosis. UHDR induced lower \u03b3H2AX accumulation and reduced 53BP1 foci formation in U87MG \u0394\u03b1BK\n                      <jats:sub>Ca<\/jats:sub>\n                      cells, suggesting impaired DNA damage recognition and repair complex assembly. Gene expression analysis revealed a shift toward upregulation of DSBR pathways and downregulation of PARP-dependent SSBR mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In conclusion, these findings identify BK\n                      <jats:sub>Ca<\/jats:sub>\n                      as a regulator of the early molecular response of glioblastoma cells to electron UHDR irradiation and provide a basis for further studies investigating BK\n                      <jats:sub>Ca<\/jats:sub>\n                      -dependent radiation responses as a target for therapeutic modulation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11060-026-05804-z","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:47:26Z","timestamp":1790095646000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BKCa channel deletion modulates the DNA damage response to electron ultra-high dose rate irradiation in glioblastoma cells"],"prefix":"10.1007","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1521-199X","authenticated-orcid":false,"given":"Kamila","family":"Maliszewska-Olejniczak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6411-5554","authenticated-orcid":false,"given":"Micha\u0142","family":"Fryc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0475-1344","authenticated-orcid":false,"given":"Agata","family":"Kustra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2731-9535","authenticated-orcid":false,"given":"Katarzyna","family":"Wiktorska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6661-0634","authenticated-orcid":false,"given":"Aleksandra","family":"Lenartowicz-Gasik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4416-3330","authenticated-orcid":false,"given":"Wojciech","family":"Soroka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4933-3829","authenticated-orcid":false,"given":"Jacek","family":"Rzadkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3824-4962","authenticated-orcid":false,"given":"Monika","family":"\u017bochowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-9557","authenticated-orcid":false,"given":"Bogusz","family":"Kulawiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7125-0715","authenticated-orcid":false,"given":"Piotr","family":"Bednarczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"5804_CR1","doi-asserted-by":"crossref","unstructured":"Desideri I, Nardone V, Morelli I, Gagliardi F, Minniti G (2024) Adv Imag Ther Neuro-Oncol 101\u2013136","DOI":"10.1007\/978-3-031-59341-3_7"},{"key":"5804_CR2","doi-asserted-by":"publisher","unstructured":"Oronsky B, Reid TR, Oronsky A, Sandhu N, Knox SJ (2021) A review of newly diagnosed glioblastoma. Front Oncol 10. https:\/\/doi.org\/10.3389\/fonc.2020.574012","DOI":"10.3389\/fonc.2020.574012"},{"issue":"4","key":"5804_CR3","doi-asserted-by":"publisher","first-page":"299","DOI":"10.3322\/caac.21613","volume":"70","author":"AC Tan","year":"2020","unstructured":"Tan AC, Ashley DM, L\u00f3pez GY, Malinzak M, Friedman HS, Khasraw M (2020) Management of glioblastoma: state of the art and future directions. CA Cancer J Clinicians 70(4):299\u2013312. https:\/\/doi.org\/10.3322\/caac.21613","journal-title":"CA Cancer J Clinicians"},{"issue":"18","key":"5804_CR4","doi-asserted-by":"publisher","first-page":"5945","DOI":"10.1158\/0008-5472.CAN-11-1245","volume":"71","author":"M Squatrito","year":"2011","unstructured":"Squatrito M, Holland EC (2011) DNA damage response and growth factor signaling pathways in gliomagenesis and therapeutic resistance. Cancer Res 71(18):5945\u20135949. https:\/\/doi.org\/10.1158\/0008-5472.CAN-11-1245","journal-title":"Cancer Res"},{"issue":"7120","key":"5804_CR5","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/nature05236","volume":"444","author":"S Bao","year":"2006","unstructured":"Bao S et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120):756\u2013760. https:\/\/doi.org\/10.1038\/nature05236","journal-title":"Nature"},{"issue":"1","key":"5804_CR6","doi-asserted-by":"publisher","first-page":"2822","DOI":"10.1038\/s41598-025-32635-1","volume":"16","author":"M Araszkiewicz","year":"2025","unstructured":"Araszkiewicz M, Korgul A, Tymi\u0144ska K, Ka\u017amierczak U, Dyka K, Chucha\u0142a P, Grzela R, Kami\u0144ska P, Kuczma R, Paterczyk B, Stankiewicz-Drogo\u0144 A, Wielgus-Kutrowska B, Kustra A, Fryc M, Bednarczyk P, Maliszewska-Olejniczak K (2025) Expression of DNA-damage response genes after exposure to high LET particles used in BNCT in glioblastoma cells with altered radiosensitivity. Sci Rep 16(1):2822. https:\/\/doi.org\/10.1038\/s41598-025-32635-1","journal-title":"Sci Rep"},{"key":"5804_CR7","doi-asserted-by":"publisher","first-page":"676575","DOI":"10.3389\/fonc.2021.676575","volume":"11","author":"K Maliszewska-Olejniczak","year":"2021","unstructured":"Maliszewska-Olejniczak K, Kaniowski D, Araszkiewicz M, Tymi\u0144ska K, Korgul A (2021) Molecular mechanisms of specific cellular DNA damage response and repair induced by the mixed radiation field during boron neutron capture therapy. Front Oncol 11:676575. https:\/\/doi.org\/10.3389\/fonc.2021.676575","journal-title":"Front Oncol"},{"key":"5804_CR8","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.radmp.2022.10.002","volume":"3","author":"L Li","year":"2022","unstructured":"Li L, Yuan Y, Zuo Y (2022) A review of the impact of FLASH radiotherapy on the central nervous system and glioma. Radiat Med Prot 3:208\u2013212. https:\/\/doi.org\/10.1016\/j.radmp.2022.10.002","journal-title":"Radiat Med Prot"},{"key":"5804_CR9","doi-asserted-by":"publisher","unstructured":"Subiel A, Romano F (2023) Recent developments in absolute dosimetry for FLASH radiotherapy. The Br J Radiol 96(1148). https:\/\/doi.org\/10.1259\/bjr.20220560","DOI":"10.1259\/bjr.20220560"},{"issue":"3","key":"5804_CR10","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.ijrobp.2022.12.018","volume":"116","author":"L Iturri","year":"2023","unstructured":"Iturri L et al (2023) Proton FLASH radiation therapy and immune infiltration: evaluation in an orthotopic glioma rat Model. Int J Radiat Oncol Biol Phys 116(3):655\u2013665. https:\/\/doi.org\/10.1016\/j.ijrobp.2022.12.018","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"5804_CR11","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1158\/1078-0432.CCR-20-0894","volume":"27","author":"P Montay-Gruel","year":"2021","unstructured":"Montay-Gruel P et al (2021) Hypofractionated FLASH-RT as an effective treatment against glioblastoma that reduces neurocognitive side effects in mice. Clin Cancer Res 27:775\u2013784. https:\/\/doi.org\/10.1158\/1078-0432.CCR-20-0894","journal-title":"Clin Cancer Res"},{"key":"5804_CR12","doi-asserted-by":"publisher","unstructured":"McGarrigle JM, Long KR, Prezado Y (2024) The FLASH effect-an evaluation of preclinical studies of ultra-high dose rate radiotherapy. Front Oncol 14. https:\/\/doi.org\/10.3389\/fonc.2024.1340190","DOI":"10.3389\/fonc.2024.1340190"},{"issue":"2","key":"5804_CR13","doi-asserted-by":"publisher","first-page":"344","DOI":"10.5603\/RPOR.a2022.0038","volume":"27","author":"N Matuszak","year":"2022","unstructured":"Matuszak N et al (2022) FLASH radiotherapy: an emerging approach in radiation therapy. Rep Pract Oncol Radiother 27(2):344\u2013351. https:\/\/doi.org\/10.5603\/RPOR.a2022.0038","journal-title":"Rep Pract Oncol Radiother"},{"issue":"4","key":"5804_CR14","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1016\/j.net.2020.09.019","volume":"53","author":"DH Jeong","year":"2021","unstructured":"Jeong DH et al (2021) Electron beam scattering device for FLASH preclinical studies with 6-MeV LINAC. Nucl Eng Technol 53(4):1289\u20131296. https:\/\/doi.org\/10.1016\/j.net.2020.09.019","journal-title":"Nucl Eng Technol"},{"issue":"3","key":"5804_CR15","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1002\/mp.15184","volume":"49","author":"AA Friedl","year":"2022","unstructured":"Friedl AA, Prise KM, Butterworth KT, Montay-Gruel P, Favaudon V (2022) Radiobiology of the FLASH effect. Med Phys 49(3):1993\u20132013. https:\/\/doi.org\/10.1002\/mp.15184","journal-title":"Med Phys"},{"key":"5804_CR16","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/164_2021_465","volume":"267","author":"K Ganser","year":"2021","unstructured":"Ganser K et al (2021) Potassium channels in cancer. Handb Exp Pharmacol 267:253\u2013275. https:\/\/doi.org\/10.1007\/164_2021_465","journal-title":"Handb Exp Pharmacol"},{"issue":"4","key":"5804_CR17","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.ceca.2013.01.001","volume":"53","author":"SMO Huber","year":"2013","unstructured":"Huber SMO (2013) Oncochannels. Cell Calcium 53(4):241\u2013255. https:\/\/doi.org\/10.1016\/j.ceca.2013.01.001","journal-title":"Cell Calcium"},{"key":"5804_CR18","doi-asserted-by":"publisher","first-page":"108488","DOI":"10.1016\/j.mrrev.2024.108488","volume":"108488","author":"K Maliszewska-Olejniczak","year":"2024","unstructured":"Maliszewska-Olejniczak K, Bednarczyk P (2024) Novel insights into the role of ion channels in cellular DNA damage response. Mutat Res Rev Mutat Res 108488:108488. https:\/\/doi.org\/10.1016\/j.mrrev.2024.108488","journal-title":"Mutat Res Rev Mutat Res"},{"issue":"6","key":"5804_CR19","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1002\/1878-0261.70167","volume":"20","author":"K Maliszewska-Olejniczak","year":"2025","unstructured":"Maliszewska-Olejniczak K, Pytlak K, Jaworowska S, Kulawiak B, Bednarczyk P (2025) Potential therapeutic targeting of BK(Ca) channels in glioblastoma treatment. Mol Oncol 20(6):1398\u20131419. https:\/\/doi.org\/10.1002\/1878-0261.70167","journal-title":"Mol Oncol"},{"key":"5804_CR20","doi-asserted-by":"publisher","unstructured":"Roth B, Huber SM (2020) Ion transport and Radioresistance. Rev Physiol Biochem Pharmacol. https:\/\/doi.org\/10.1007\/112_2020_33","DOI":"10.1007\/112_2020_33"},{"issue":"7","key":"5804_CR21","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s00249-016-1136-z","volume":"45","author":"B Stegen","year":"2016","unstructured":"Stegen B et al (2016) K(+) channel signaling in irradiated tumor cells. Eur Biophys J 45(7):585\u2013598. https:\/\/doi.org\/10.1007\/s00249-016-1136-z","journal-title":"Eur Biophys J"},{"issue":"9","key":"5804_CR22","doi-asserted-by":"publisher","first-page":"6866","DOI":"10.1002\/jcp.26448","volume":"233","author":"P Rosa","year":"2018","unstructured":"Rosa P et al (2018) BK channels blockage inhibits hypoxia-induced migration and chemoresistance to cisplatin in human glioblastoma cells. J Cell Physiol 233(9):6866\u20136877. https:\/\/doi.org\/10.1002\/jcp.26448","journal-title":"J Cell Physiol"},{"issue":"1","key":"5804_CR23","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.radonc.2011.05.069","volume":"101","author":"M Steinle","year":"2011","unstructured":"Steinle M et al (2011) Ionizing radiation induces migration of glioblastoma cells by activating BK K(+) channels. Radiother Oncol 101(1):122\u2013126. https:\/\/doi.org\/10.1016\/j.radonc.2011.05.069","journal-title":"Radiother Oncol"},{"issue":"5","key":"5804_CR24","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.4049\/jimmunol.1102965","volume":"189","author":"L Ge","year":"2012","unstructured":"Ge L et al (2012) Glioma big potassium channel expression in human cancers and possible T cell epitopes for their immunotherapy. J Immunol 189(5):2625\u20132634. https:\/\/doi.org\/10.4049\/jimmunol.1102965","journal-title":"J Immunol"},{"issue":"9","key":"5804_CR25","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1007\/s00424-023-02833-9","volume":"475","author":"B Kulawiak","year":"2023","unstructured":"Kulawiak B, \u017bochowska M, Bednarczyk P, Galuba A, Stroud DA, Szewczyk A (2023) Loss of the large conductance calcium-activated potassium channel causes an increase in mitochondrial reactive oxygen species in glioblastoma cells. Pflugers Arch 475(9):1045\u20131060. https:\/\/doi.org\/10.1007\/s00424-023-02833-9","journal-title":"Pflugers Arch"},{"key":"5804_CR26","doi-asserted-by":"publisher","first-page":"104","DOI":"10.3389\/fphys.2015.00104","volume":"6","author":"E Balderas","year":"2015","unstructured":"Balderas E, Zhang J, Stefani E, Toro L (2015) Mitochondrial BKCa channel. Front Physiol 6:104. https:\/\/doi.org\/10.3389\/fphys.2015.00104","journal-title":"Front Physiol"},{"key":"5804_CR27","doi-asserted-by":"publisher","first-page":"152","DOI":"10.3389\/fncel.2015.00152","volume":"9","author":"L Catacuzzeno","year":"2015","unstructured":"Catacuzzeno L et al (2015) Reconciling the discrepancies on the involvement of large-conductance Ca(2+)-activated K channels in glioblastoma cell migration. Front Cell Neurosci 9:152. https:\/\/doi.org\/10.3389\/fncel.2015.00152","journal-title":"Front Cell Neurosci"},{"key":"5804_CR28","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1093\/bjr\/tqaf245","volume":"99","author":"WS Thomas","year":"2026","unstructured":"Thomas WS, Kulkarni S, Ilina A, Reed M, Pogue BW (2026) In vitro oxygen concentration alters reactive oxygen species yields with minor plasmid DNA damage change at ultra-high-dose rate. The Br J Radiol 99:169\u2013175. https:\/\/doi.org\/10.1093\/bjr\/tqaf245","journal-title":"The Br J Radiol"},{"issue":"1","key":"5804_CR29","doi-asserted-by":"publisher","first-page":"3824","DOI":"10.1038\/s41598-025-03824-9","volume":"15","author":"K Maliszewska-Olejniczak","year":"2025","unstructured":"Maliszewska-Olejniczak K, Kustra A, Szyma\u0144ski W, D\u0105browska-Hulka A, \u017bochowska M, Kulawiak B, Bednarczyk P (2025) Bkca channel as a novel regulator of cellular DNA damage response in human bronchial epithelial cells in the presence of particulate matter. Sci Rep 15(1):3824. https:\/\/doi.org\/10.1038\/s41598-025-03824-9","journal-title":"Sci Rep"},{"issue":"12","key":"5804_CR30","doi-asserted-by":"publisher","first-page":"14259","DOI":"10.18632\/oncotarget.7423","volume":"7","author":"L Edalat","year":"2016","unstructured":"Edalat L, Stegen B, Klumpp L, Haehl E, Schilbach K, Lukowski R, K\u00fchnle M, Bernhardt G, Buschauer A, Zips D, Ruth P, Huber SM (2016) BK K+ channel blockade inhibits radiation-induced migration\/brain infiltration of glioblastoma cells. Oncotarget 7(12):14259\u201314278. https:\/\/doi.org\/10.18632\/oncotarget.7423","journal-title":"Oncotarget"},{"key":"5804_CR31","doi-asserted-by":"publisher","unstructured":"Bednarczyk P et al (2013) Putative structural and functional coupling of the mitochondrial BKCa channel to the respiratory chain. PLoS One 8(6):e68125. https:\/\/doi.org\/10.1371\/journal.pone.0068125","DOI":"10.1371\/journal.pone.0068125"},{"issue":"4","key":"5804_CR32","doi-asserted-by":"publisher","first-page":"812","DOI":"10.2144\/03354mt02","volume":"35","author":"CJ Miller","year":"2003","unstructured":"Miller CJ et al (2003) Mycoplasma infection significantly alters microarray gene expression profiles. Biotechniques 35(4):812\u2013814. https:\/\/doi.org\/10.2144\/03354mt02","journal-title":"Biotechniques"},{"issue":"1","key":"5804_CR33","doi-asserted-by":"publisher","first-page":"62","DOI":"10.2478\/pjmpe-2025-0006","volume":"31","author":"A Lenartowicz-Gasik","year":"2025","unstructured":"Lenartowicz-Gasik A, Misiarz A, Adrich P, Wronka S, Piotrowski T, Pawa\u0142owski B, Nowaczyk P, Trzuskowski J, Rzadkiewicz J (2025) Experimental verification of the applicability of the AQURE IOERT accelerator for FLASH radiotherapy. Pol J Med Phys Eng 31(1):62\u201372. https:\/\/doi.org\/10.2478\/pjmpe-2025-0006","journal-title":"Pol J Med Phys Eng"},{"key":"5804_CR34","doi-asserted-by":"publisher","first-page":"110507","DOI":"10.1016\/j.radonc.2024.110507","volume":"200","author":"TT B\u00f6hlen","year":"2024","unstructured":"B\u00f6hlen TT et al (2024) Recording and reporting of ultra-high dose rate \u201cFLASH\u201d delivery for preclinical and clinical settings. Radiother Oncol 200:110507. https:\/\/doi.org\/10.1016\/j.radonc.2024.110507","journal-title":"Radiother Oncol"},{"key":"5804_CR35","doi-asserted-by":"publisher","unstructured":"Lenartowicz-Gasik A, Misiarz A, Markopolski V, Walo M, Gryczka U, Bu\u0142ka S, Pawa\u0142owski B, Kruszyna-Mochalska M, Rzadkiewicz J (2024) Verification of real-time dosimetry of ultra-high dose rate beams at AQURE FLASH RT on the sample surface. Pol J Med Phys Eng 30(4). https:\/\/doi.org\/10.2478\/pjmpe-2024-0038","DOI":"10.2478\/pjmpe-2024-0038"},{"key":"5804_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.24425\/mms.2025.155811","volume":"32","author":"A Lenartowicz-Gasik","year":"2025","unstructured":"Lenartowicz-Gasik A et al (2025) Iort aqure in flash mode: dosimetric control in breast cancer cell in vitro experiments. Metrol Meas Syst 32:1\u201315. https:\/\/doi.org\/10.24425\/mms.2025.155811","journal-title":"Metrol Meas Syst"},{"key":"5804_CR37","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s40659-025-00629-y","volume":"58","author":"A Kustra","year":"2025","unstructured":"Kustra A, Zaj\u0105c M, Bednarczyk P, Maliszewska-Olejniczak K (2025) Exposure to polystyrene nanoparticles leads to dysfunction in DNA repair mechanisms in caco-2 cells. Biol Res 58:49. https:\/\/doi.org\/10.1186\/s40659-025-00629-y","journal-title":"Biol Res"},{"issue":"101880","key":"5804_CR38","doi-asserted-by":"publisher","first-page":"101880","DOI":"10.1016\/j.mito.2024.101880","volume":"76","author":"K Maliszewska-Olejniczak","year":"2024","unstructured":"Maliszewska-Olejniczak K et al (2024) Deficiency of the BK(Ca) potassium channel displayed significant implications for the physiology of the human bronchial epithelium. Mitochondrion 76(101880):101880. https:\/\/doi.org\/10.1016\/j.mito.2024.101880","journal-title":"Mitochondrion"},{"key":"5804_CR39","doi-asserted-by":"publisher","first-page":"4963","DOI":"10.1038\/s41596-021-00615-0","volume":"16","author":"N Brix","year":"2021","unstructured":"Brix N, Samaga D, Belka C, Zitzelsberger H, Lauber K (2021) Analysis of clonogenic growth in vitro. Nat Protoc 16:4963\u20134991. https:\/\/doi.org\/10.1038\/s41596-021-00615-0","journal-title":"Nat Protoc"},{"issue":"5","key":"5804_CR40","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1038\/nprot.2006.339","volume":"1","author":"NA Franken","year":"2006","unstructured":"Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C (2006) Clonogenic assay of cells in vitro. Nat Protoc 1(5):2315\u20132319. https:\/\/doi.org\/10.1038\/nprot.2006.339","journal-title":"Nat Protoc"},{"key":"5804_CR41","doi-asserted-by":"publisher","unstructured":"Maliszewska-Olejniczak K, Dr\u00f3\u017cd A, Walu M, Dorosz M, Gryzi\u0144ski MA (2020) Immunofluorescence imaging of DNA damage and repair foci in human colon cancer cells. J Vis Exp (160). https:\/\/doi.org\/10.3791\/61399-v","DOI":"10.3791\/61399-v"},{"key":"5804_CR42","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/nrc.2015.2","volume":"16","author":"WP Roos","year":"2016","unstructured":"Roos WP, Thomas AD, Kaina B (2016) DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer 16:20\u201333. https:\/\/doi.org\/10.1038\/nrc.2015.2","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"5804_CR43","first-page":"771","volume":"92","author":"JYJ Wang","year":"2019","unstructured":"Wang JYJ (2019) Cell death response to DNA damage. Yale J Biol Med 92(4):771\u2013779","journal-title":"Yale J Biol Med"},{"issue":"8","key":"5804_CR44","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1093\/neuonc\/noae072","volume":"26","author":"R Rahman","year":"2024","unstructured":"Rahman R, Shi DD, Reitman ZJ, Hamerlik P, de Groot JF, Haas-Kogan DA, D\u2019andrea AD, Sulman EP, Tanner K, Agar NYR, Sarkaria JN, Tinkle CL, Bindra RS, Mehta MP, Wen PY (2024) DNA damage response in brain tumors: a society for Neuro Oncol consensus review on mechanisms and translational efforts in neuro-oncology. Neuro-Oncology 26(8):1367\u20131387. https:\/\/doi.org\/10.1093\/neuonc\/noae072","journal-title":"Neuro-Oncology"},{"issue":"5","key":"5804_CR45","doi-asserted-by":"publisher","first-page":"2546","DOI":"10.3390\/ijms25052546","volume":"25","author":"A Borghini","year":"2024","unstructured":"Borghini A et al (2024) FLASH radiotherapy: expectations, challenges, and current knowledge. Int J Mol Sci 25(5):2546. https:\/\/doi.org\/10.3390\/ijms25052546","journal-title":"Int J Mol Sci"},{"key":"5804_CR46","doi-asserted-by":"publisher","unstructured":"Del Debbio F et al (2023) An insight into hypothesized biological mechanisms contributing to the flash effect. Front Phys 11. https:\/\/doi.org\/10.3389\/fphy.2023.1201708","DOI":"10.3389\/fphy.2023.1201708"},{"key":"5804_CR47","doi-asserted-by":"publisher","first-page":"1575678","DOI":"10.3389\/fcell.2025.1575678","volume":"13","author":"G Rosini","year":"2025","unstructured":"Rosini G, Ciarrocchi E, D\u2019orsi B (2025) Mechanisms of the FLASH effect: current insights and advances. Front Cell Dev Biol 13:1575678. https:\/\/doi.org\/10.3389\/fcell.2025.1575678","journal-title":"Front Cell Dev Biol"},{"issue":"10","key":"5804_CR48","doi-asserted-by":"publisher","first-page":"5621","DOI":"10.3390\/ijms23105621","volume":"23","author":"M Maszczyk","year":"2022","unstructured":"Maszczyk M, Banach K, Karkoszka M, Rzepka Z, Rok J, Beberok A, Wrze\u015bniok D (2022) Chemosensitization of U-87 MG glioblastoma cells by neobavaisoflavone towards doxorubicin and etoposide. Int J Mol Sci 23(10):5621. https:\/\/doi.org\/10.3390\/ijms23105621","journal-title":"Int J Mol Sci"},{"key":"5804_CR49","doi-asserted-by":"publisher","unstructured":"Ghorai A, Singh B, Dutt S (2024) Biphasic DNA damage and non-canonical replication stress response govern radiation-induced senescence in glioblastoma. J Cell Sci 137(24). https:\/\/doi.org\/10.1242\/jcs.261844","DOI":"10.1242\/jcs.261844"},{"issue":"6","key":"5804_CR50","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1158\/1078-0432.ccr-19-1440","volume":"26","author":"C Fouillade","year":"2020","unstructured":"Fouillade C, Curras-Alonso S, Giuranno L, Quelennec E, Heinrich S, Bonnet-Boissinot S, Beddok A, Leboucher S, Karakurt HU, Bohec M, Baulande S, Vooijs M, Verrelle P, Dutreix M, Londo\u00f1o-Vallejo A, Favaudon V (2020) FLASH irradiation spares lung progenitor cells and limits the incidence of radio-induced senescence. Clin Cancer Res 26(6):1497\u20131506. https:\/\/doi.org\/10.1158\/1078-0432.ccr-19-1440","journal-title":"Clin Cancer Res"},{"key":"5804_CR51","doi-asserted-by":"publisher","unstructured":"Chen J et al (2024) Aberrant ATM signaling and homology-directed DNA repair as a vulnerability of p53-mutant GBM to AZD1390-mediated radiosensitization. Sci Transl Med 16(734):eadj5962. https:\/\/doi.org\/10.1126\/scitranslmed.adj5962","DOI":"10.1126\/scitranslmed.adj5962"},{"key":"5804_CR52","doi-asserted-by":"publisher","first-page":"101050","DOI":"10.1016\/j.ctro.2025.101050","volume":"56","author":"TL Schanel","year":"2026","unstructured":"Schanel TL, Kumar M, Nassour-Caswell LC, Cherakara S, Pandit R, Beierle AM, Anderson JC, Hicks PH, Cardan R, Hjelmeland AB, Willey CD (2026) No differences in therapeutic efficacy while sparing healthy tissue for orthotopic glioblastoma patient-derived xenografts in context of proton FLASH. Clin Transl Radiat Oncol 56:101050. https:\/\/doi.org\/10.1016\/j.ctro.2025.101050","journal-title":"Clin Transl Radiat Oncol"}],"container-title":["Journal of Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-026-05804-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11060-026-05804-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-026-05804-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:01:31Z","timestamp":1792087291000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11060-026-05804-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["5804"],"URL":"https:\/\/doi.org\/10.1007\/s11060-026-05804-z","relation":{},"ISSN":["0167-594X","1573-7373"],"issn-type":[{"value":"0167-594X","type":"print"},{"value":"1573-7373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"16 July 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors of the manuscript agree to article publication.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"95"}}