{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T10:10:47Z","timestamp":1775124647816,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K12578"],"award-info":[{"award-number":["24K12578"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23ama221125h0001"],"award-info":[{"award-number":["23ama221125h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Malignant transformation of mature cystic teratoma (MTMCT) of the ovary is a rare but aggressive malignancy for which no standardized chemotherapy or effective targeted therapies currently exist. To identify therapeutic vulnerabilities in MTMCT, we performed a genome\u2010wide CRISPR\u2010Cas9 knockout screen using the MTMCT\u2010derived NOSCC1 cell line. Two parallel selective pressures were applied: in\u00a0vivo tumorigenicity in immunodeficient mice and cisplatin exposure in\u00a0vitro. From this screen, 67 negatively selected genes were identified, among which SOD1 and NDUFB4 emerged as top candidates based on high basal expression levels and clinical relevance. Integration with spatial transcriptomic data from three independent MTMCT patient tumors further supported the prioritization of these targets. SOD1 was selected for further investigation due to the availability of known pharmacological inhibitors. Both siRNA\u2010mediated knockdown and small\u2010molecule inhibition of SOD1 using LCS\u20101 significantly suppressed MTMCT cell proliferation in\u00a0vitro by inducing oxidative stress and impairing cell cycle progression. This antiproliferative effect was reversed by co\u2010treatment with\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetylcysteine, a reactive oxygen species scavenger. In\u00a0vivo validation using patient\u2010derived xenograft models demonstrated that oral administration of LCS\u20101 led to significant tumor growth suppression and increased expression of apoptotic and DNA damage markers, including cleaved caspase\u20103 and \u03b3H2AX. These findings establish SOD1 as a critical vulnerability in MTMCT and provide preclinical evidence supporting redox modulation as a therapeutic strategy for this highly chemoresistant and understudied ovarian cancer subtype. Our integrative approach combining functional genomics, spatial transcriptomics, and pharmacologic validation offers a framework for the discovery of novel targets in rare gynecologic malignancies.\n                  <\/jats:p>","DOI":"10.1111\/cas.70315","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T07:59:49Z","timestamp":1768377589000},"page":"983-995","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In\u2010Tumor\n                    <scp>CRISPR<\/scp>\n                    \u2010Cas9 Knockout Screening and Novel Therapy Development for Malignant Transformation of Ovarian Teratoma"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3130-3736","authenticated-orcid":false,"given":"Satoshi","family":"Tamauchi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1484-4872","authenticated-orcid":false,"given":"Kosuke","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Institute for Advanced Research Nagoya University  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Xinyuan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0789-5102","authenticated-orcid":false,"given":"Akira","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Institute for Advanced Research Nagoya University  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8662-9421","authenticated-orcid":false,"given":"Nobuhisa","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4546-9606","authenticated-orcid":false,"given":"Kaoru","family":"Niimi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5262-8479","authenticated-orcid":false,"given":"Yusuke","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Oncology National Cancer Center Research Institute  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0493-1825","authenticated-orcid":false,"given":"Hiroaki","family":"Kajiyama","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"issue":"1","key":"e_1_2_13_2_1","first-page":"22","article-title":"Mature Cystic Teratoma: A Linicopathologic Evaluation of 517 Cases and Review of the Literature","volume":"84","author":"Comerci J. T.","year":"1994","journal-title":"Obstetrics & Gynecology"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70306-1"},{"issue":"1","key":"e_1_2_13_4_1","first-page":"1","article-title":"Squamous Cell Carcinoma Transformation in Mature Cystic Teratoma of the Ovary: A Systematic Review","volume":"19","author":"Li C.","year":"2019","journal-title":"BMC Cancer"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198905000-00007"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.12936"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gore.2020.100632"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijscr.2023.108329"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.14596"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2023.04.003"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-023-11626-3"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1422165112"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.70022"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2024.114266"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1160548"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.123.001697"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15041167"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4002"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2803"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.07.017"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1103-9"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-24-0512"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.105626"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2023"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000002932"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14030213"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0171"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2011.04.009"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204705"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac7041"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70315","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.70315","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70315","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T09:27:25Z","timestamp":1775122045000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/cas.70315"],"URL":"https:\/\/doi.org\/10.1111\/cas.70315","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]},"assertion":[{"value":"2025-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}