{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:15:41Z","timestamp":1785424541228,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,28]]},"group-title":"Cancer Biology","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R50CA211241"],"award-info":[{"award-number":["R50CA211241"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01CA266172"],"award-info":[{"award-number":["R01CA266172"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01CA294651"],"award-info":[{"award-number":["R01CA294651"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30CA047904"],"award-info":[{"award-number":["P30CA047904"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TL1TR001858"],"award-info":[{"award-number":["TL1TR001858"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    ATR activation following DNA damage from cancer treatments such as radiation can mitigate anticancer efficacy, making ATR inhibitors (ATRi) an attractive therapeutic.\n                    <jats:italic>In vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies have shown enhanced tumor cell radiosensitivity with the ATRi ceralasertib, elimusertib, and berzosertib, however, the potentiating effect of ATRi on ionizing radiation (IR) through immune-based mechanisms has only been studied with ceralasertib.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We aimed to determine if antitumor immune responses observed with ceralasertib in combination with IR extend to the other ATRi class members in the preclinical CT26 mouse model. We also examined the relationship between exposure and immune stimulation, efficacy and survival outcomes of each ATRi when combined with IR.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Ceralasertib and elimusertib, not berzosertib, synergized with IR in a dose and schedule-dependent manner to modify tumor antigen-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell populations in the draining lymph node. Transient ATRi therapy, combined with IR, enhances antitumor efficacy, promoted tumor shrinkage, and increased survival. ATRi elicited differential inflammatory gene induction and dose-dependent unique cytotoxicity profiles\n                    <jats:italic>in vitro<\/jats:italic>\n                    .\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The immune mediated antitumor effect of ATRi combined with radiation is dose and schedule dependent, and while likely a class effect, may differ between ATRi compounds.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.25.727700","type":"posted-content","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T22:45:14Z","timestamp":1780008314000},"source":"Crossref","is-referenced-by-count":0,"title":["Transient ATR inhibition following ionizing radiation enhances immune-mediated antitumor response and survival"],"prefix":"10.64898","author":[{"given":"Joshua","family":"Deppas","sequence":"first","affiliation":[{"name":"Cancer Therapeutics Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian F.","family":"Kiesel","sequence":"additional","affiliation":[{"name":"Cancer Therapeutics Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank P.","family":"Vendetti","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinakin","family":"Pandya","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxia","family":"Guo","sequence":"additional","affiliation":[{"name":"Cancer Therapeutics Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine L.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Biostatistics Facility, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Bakkenist","sequence":"additional","affiliation":[{"name":"Cancer Therapeutics Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meysam","family":"Tavakoli","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"diMayorca","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed M","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Clump","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Radiation Oncology, School of Medicine, West Virginia University, Morgantown, West Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9672-0886","authenticated-orcid":false,"given":"Christopher J.","family":"Bakkenist","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8978-9401","authenticated-orcid":false,"given":"Jan H.","family":"Beumer","sequence":"additional","affiliation":[{"name":"Cancer Therapeutics Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Oncology, Johns Hopkins University School of Medicine and Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, Maryland, 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