{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:50:08Z","timestamp":1790819408946,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Foundation","doi-asserted-by":"publisher","award":["P32103-B"],"award-info":[{"award-number":["P32103-B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>To overcome the resistance to radiotherapy in chondrosarcomas, the prevention of efficient DNA repair with an additional treatment was explored for particle beams as well as reference X-ray irradiation. The combined treatment with DNA repair inhibitors\u2014with a focus on ATRi VE-821\u2014and proton or carbon ions irradiation was investigated regarding cell viability, proliferation, cell cycle distribution, MAPK phosphorylation, and the expression of key DNA repair genes in two human chondrosarcoma cell lines. Pre-treatment with the PARPis Olaparib or Veliparib, the ATMi Ku-55933, and the ATRi VE-821 resulted in a dose-dependent reduction in viability, whereas VE-821 has the most efficient response. Quantification of \u03b3H2AX phosphorylation and protein expression of the DNA repair pathways showed a reduced regenerative capacity after irradiation. Furthermore, combined treatment with VE-821 and particle irradiation increased MAPK phosphorylation and the expression of apoptosis markers. At the gene expression and at the protein expression\/phosphorylation level, we were able to demonstrate the preservation of DNA damage after combined treatment. The present data showed that the combined treatment with ATMi VE-821 increases the radiosensitivity of human chondrosarcoma cells in vitro and significantly suppresses efficient DNA repair mechanisms, thus improving the efficiency of radiotherapy.<\/jats:p>","DOI":"10.3390\/ijms24032315","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T03:53:18Z","timestamp":1674618798000},"page":"2315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The ATR Inhibitor VE-821 Enhances the Radiosensitivity and Suppresses DNA Repair Mechanisms of Human Chondrosarcoma Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3156-7902","authenticated-orcid":false,"given":"Birgit","family":"Lohberger","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Trauma, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Gl\u00e4nzer","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Eck","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Stasny","sequence":"additional","affiliation":[{"name":"MedAustron Ion Therapy Center, 2700 Wiener Neustadt, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Falkner","sequence":"additional","affiliation":[{"name":"MedAustron Ion Therapy Center, 2700 Wiener Neustadt, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-2325","authenticated-orcid":false,"given":"Andreas","family":"Leithner","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-3877","authenticated-orcid":false,"given":"Dietmar","family":"Georg","sequence":"additional","affiliation":[{"name":"MedAustron Ion Therapy Center, 2700 Wiener Neustadt, Austria"},{"name":"Department of Radiation Oncology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"ref_1","first-page":"264","article-title":"Chondrosarcoma","volume":"Volume 5","author":"Fletcher","year":"2013","journal-title":"World Health Organization Classification of Tumours of Soft Tissue and Bone"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1302\/0301-620X.101B3.BJJ-2018-0881.R1","article-title":"Locally recurrent chondrosarcoma of the pelvis and limbs can only be controlled by wide local excision","volume":"101-B","author":"Laitinen","year":"2019","journal-title":"Bone Joint J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zaj\u0105c, A.E., Kope\u0107, S., Szostakowski, B., Spa\u0142ek, M.J., Fiedorowicz, M., Bylina, E., Filipowicz, P., Szumera-Cie\u0107kiewicz, A., Tysarowski, A., and Czarnecka, A.M. 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