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Combining surgery with radiotherapy, particularly using carbon ions (C-ions) for their higher biological effectiveness, improves local control and survival rates. To investigate cellular mechanisms, two human sacral chordoma cell lines were irradiated with varying C-ions doses. Growth, cell cycle, DNA damage response, and protein phosphorylation were analyzed using flow cytometry, protein, and gene expression profiling. The potential of combining treatment with the ALK\/MET inhibitor crizotinib to enhance radiosensitivity was also evaluated. C-ions irradiation resulted in a slight dose-dependent decrease in proliferation, a clear G\n                    <jats:sub>2<\/jats:sub>\n                    \/M cell cycle arrest, and a significant activation of key regulators involved in DNA repair and damage response. The ALK\/MET inhibitor crizotinib, considered a potential treatment for chordomas, reduced proliferation markers and modulated important genes related to DNA repair and cell cycle regulation, with\n                    <jats:italic>CDC20<\/jats:italic>\n                    and\n                    <jats:italic>FOXO4<\/jats:italic>\n                    being particularly significant. The phosphorylation of key regulators involved in DNA repair and damage prevention, as well as MAPKs activated by C-ions irradiation, was partially inhibited by the combination treatment with crizotinib. While crizotinib shows promise as a therapeutic agent for sacral chordomas, its capacity to enhance radiosensitivity appears limited.\n                  <\/jats:p>","DOI":"10.1007\/s12032-025-03172-8","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T06:53:36Z","timestamp":1766559216000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of crizotinib as radiosensitizer in sacral chordoma cells: effects of combined carbon ion particle therapy"],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3156-7902","authenticated-orcid":false,"given":"Birgit","family":"Lohberger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietmar","family":"Gl\u00e4nzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Etschmaier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slave","family":"Trajanoski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Leithner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Rinner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietmar","family":"Georg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"3172_CR1","doi-asserted-by":"publisher","first-page":"2943","DOI":"10.1002\/1097-0142(19931115)72:10<2943::AID-CNCR2820721014>3.0.CO;2-6","volume":"72","author":"A Mitchell","year":"1993","unstructured":"Mitchell A, Scheithauer BW, Unni KK, Forsyth PJ, Wold LE, McGivney DJ. 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