{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:34:55Z","timestamp":1790192095087,"version":"4.1.0"},"posted":{"date-parts":[[2023,4,5]]},"group-title":"Cancer Biology","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21CA164592"],"award-info":[{"award-number":["R21CA164592"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P50CA62924"],"award-info":[{"award-number":["P50CA62924"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30CA006973"],"award-info":[{"award-number":["P30CA006973"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Sol Goldman Pancreatic Cancer Research Center"},{"name":"PanCan\/AACR Innovation Award"},{"name":"The STRINGER Foundation"},{"name":"Casimir H. Zgonina Family Endowment for Pancreatic Cancer Research"},{"name":"Dennis Troper and Susan Wojcicki"},{"name":"Dick Knox\/Cliff Minor Fund"},{"name":"Edward A. Goldsmith Pancreatic Cancer Research Fund"},{"name":"Elaine Crispen Sawyer Endowment"},{"name":"Elaine T. Koehler Pancreatic Cancer Research Fund"},{"name":"Eve Stancik Memorial Fund"},{"name":"George Rubis Endowment for Pancreatic Cancer Research"},{"name":"Hilda Buchfeller Yost Young Investigator's Fund"},{"name":"James S. McFarland Endowment for Pancreatic Cancer Research"},{"name":"John J. Lussier Pancreatic Cancer Research Fund"},{"name":"Linda C. Talecki Gallbladder Cancer Research Fund"},{"name":"Mary M. Graf Memorial Endowment Fund for Gallbladder Cancer"},{"name":"Mary Lou Wootton Endowment"},{"name":"Professor J. Mayo Greenberg and Dr. Samuel L. 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Through both bioinformatics and cytogenetics analyses, we found that CRISPR-Cas9-induced DSBs triggered ongoing chromosomal rearrangements, with 87% of structural variants not directly produced from the initial CRISPR-Cas9-induced DSBs, and chromosomal instability (CIN) peaking before cell death. By comparing the cytotoxicity of CRISPR-Cas9- to radiation-induced DSBs, we demonstrate that the number of DSBs required to achieve equitoxic effects was \u223c3 times higher for radiation than CRISPR-Cas9. Finally, we show that PC cells that had survived CRISPR-Cas9 targeting retained susceptibility to subsequent CRISPR-Cas9-induced DSBs at different genomic sites with &gt;87% growth inhibition. Together, our data support the therapeutic potential of CRISPR-Cas9 as an anti-cancer strategy.<\/jats:p>","DOI":"10.1101\/2023.04.03.535384","type":"posted-content","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T20:30:27Z","timestamp":1680726627000},"source":"Crossref","is-referenced-by-count":3,"title":["Simultaneous CRISPR-Cas9-induced double strand breaks are lethal in models of pancreatic cancer"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5281-1978","authenticated-orcid":false,"given":"Selina Shiqing K.","family":"Teh","sequence":"first","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil","family":"Kotwal","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School 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