{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:16:27Z","timestamp":1783476987728,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"4-5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020111","name":"Therapeutic Innovation Australia","doi-asserted-by":"publisher","award":["TIA 2019003"],"award-info":[{"award-number":["TIA 2019003"]}],"id":[{"id":"10.13039\/501100020111","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009845","name":"Ovarian Cancer Research Foundation","doi-asserted-by":"publisher","award":["GA\u20102024\u201002"],"award-info":[{"award-number":["GA\u20102024\u201002"]}],"id":[{"id":"10.13039\/100009845","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["OC220022"],"award-info":[{"award-number":["OC220022"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008018","name":"Victorian Cancer Agency","doi-asserted-by":"publisher","award":["MCRF19046"],"award-info":[{"award-number":["MCRF19046"]}],"id":[{"id":"10.13039\/100008018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008018","name":"Victorian Cancer Agency","doi-asserted-by":"publisher","award":["MCRF23014"],"award-info":[{"award-number":["MCRF23014"]}],"id":[{"id":"10.13039\/100008018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000947","name":"Australian Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015803","name":"BC Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022499","name":"Janet D. Cottrelle Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022499","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009326","name":"Cancer Research Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Low\u2010grade serous ovarian carcinoma (LGSOC) is a rare, indolent ovarian cancer subtype with limited effective therapies. Approximately 40% of cases lack canonical MAPK\/ERK or PI3K\/AKT\/mTOR pathway alterations and are classified as having no specific molecular profile (NSMP). These patients have poor responses to chemotherapy, MEK inhibitors, and hormonal therapies, highlighting the need for alternative strategies. This study aimed to identify novel therapeutic targets in NSMP LGSOC. A high\u2010throughput drug screen of 3,436 compounds (including FDA\u2010approved, clinically tested, and investigational agents) was conducted across 12 LGSOC and one control ovarian epithelial cell line. EGFR inhibitors emerged as selective hits in NSMP cell lines and were further tested in two NSMP and two MAPK\u2010mutant lines in combination with standard\u2010of\u2010care chemotherapy agents, carboplatin and paclitaxel. EGFR expression was assessed using RNA sequencing, DNA methylation profiling, and immunohistochemistry in primary tumors, followed by survival analysis based on expression levels. Unsupervised clustering of drug response data revealed subtype\u2010specific vulnerabilities, with EGFR inhibitors showing marked cytotoxicity in all five NSMP lines (robust\n                    <jats:italic>Z<\/jats:italic>\n                    \u2010score\u2009\u2264\u2009\u22122), and minimal activity in MAPK\u2010 and\n                    <jats:italic>USP9X<\/jats:italic>\n                    \u2010mutant lines. EGFR inhibitors (avitinib, AV\u2010412) showed selective, low\u2010dose synergy with standard\u2010of\u2010care chemotherapy in NSMP models, with minimal and inconsistent effects in MAPK\u2010mutant lines. NSMP tumors showed elevated\n                    <jats:italic>EGFR<\/jats:italic>\n                    mRNA and EGFR protein expression, associated with poor survival, advanced disease stage, and peritoneal involvement, and inversely correlated with MAPK mutations. These findings position EGFR overexpression as a defining and targetable feature of NSMP LGSOC and support further preclinical validation of EGFR inhibitors as a treatment strategy for this understudied cancer subtype. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70075","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T10:03:22Z","timestamp":1778839402000},"page":"446-461","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identifying therapeutic targets in low\u2010grade serous ovarian carcinomas with no specific molecular profile"],"prefix":"10.1002","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7863-807X","authenticated-orcid":false,"given":"Kathleen I","family":"Pishas","sequence":"first","affiliation":[{"name":"Peter MacCallum Cancer Centre  Melbourne Victoria Australia"},{"name":"The Sir Peter MacCallum Department of Oncology The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla J","family":"Cowley","sequence":"additional","affiliation":[{"name":"Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-5009","authenticated-orcid":false,"given":"Evanny","family":"Marinovic","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6615-2037","authenticated-orcid":false,"given":"Martin","family":"K\u00f6bel","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Llaurado\u2010Fernandez","sequence":"additional","affiliation":[{"name":"Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Clinical Research, BC Cancer  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Clinical Research, BC Cancer  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2085-8326","authenticated-orcid":false,"given":"Shaine Chenxin","family":"Bao","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8742-963X","authenticated-orcid":false,"given":"Dalia","family":"Mizikovsky","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9334-8107","authenticated-orcid":false,"given":"Nathan J","family":"Palpant","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-1413","authenticated-orcid":false,"given":"Raunak","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery Uniformed Services University of the Health Sciences  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6949-6188","authenticated-orcid":false,"given":"Robert","family":"Vary","sequence":"additional","affiliation":[{"name":"Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-4820","authenticated-orcid":false,"given":"Jennii","family":"Luu","sequence":"additional","affiliation":[{"name":"Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6795-6646","authenticated-orcid":false,"given":"Liliane","family":"Meunier","sequence":"additional","affiliation":[{"name":"Canadian Ovarian Experimental Unified Resource Centre hospitalier de l'Universit\u00e9 de Montr\u00e9al (CHUM)  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4048-1553","authenticated-orcid":false,"given":"Timothy","family":"Semple","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre  Melbourne Victoria Australia"},{"name":"Genomics Core, Peter MacCallum Cancer Centre  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3881-7396","authenticated-orcid":false,"given":"Pilar","family":"Blancafort","sequence":"additional","affiliation":[{"name":"Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research The University of Western Australia  Perth Western Australia Australia"},{"name":"School of Human Sciences The University of Western Australia  Perth Western Australia Australia"},{"name":"Centre for Medical Research The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Golden","sequence":"additional","affiliation":[{"name":"Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research The University of Western Australia  Perth Western Australia Australia"},{"name":"Centre for Medical Research The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4860-9232","authenticated-orcid":false,"given":"Paul A","family":"Cohen","sequence":"additional","affiliation":[{"name":"Centre for Medical Research The University of Western Australia  Perth Western Australia Australia"},{"name":"UWA Medical School, Obstetrics and Gynaecology The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"Carey","sequence":"additional","affiliation":[{"name":"Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Clinical Research, BC Cancer  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7773-4155","authenticated-orcid":false,"given":"Ian G","family":"Campbell","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre  Melbourne Victoria Australia"},{"name":"The Sir Peter MacCallum Department of Oncology The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9136-1781","authenticated-orcid":false,"given":"Kaylene J","family":"Simpson","sequence":"additional","affiliation":[{"name":"The Sir Peter MacCallum Department of Oncology The University of Melbourne  Melbourne Victoria Australia"},{"name":"Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1170-4690","authenticated-orcid":false,"given":"Dane","family":"Cheasley","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre  Melbourne Victoria Australia"},{"name":"The Sir Peter MacCallum Department of Oncology The University of Melbourne  Melbourne Victoria Australia"},{"name":"Centre for Medical Research The University of Western Australia  Perth Western Australia Australia"},{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.12.033"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5545"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-022-00288-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-2222"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-2224"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100212"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5438"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14020416"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2021.11.019"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.0632"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2012.02.037"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25929"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70253-5"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.5561"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-25-00112"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2023.06.466"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-019-0725-1"},{"key":"e_1_2_8_19_1","first-page":"2235","article-title":"Differences in MEK inhibitor efficacy in molecularly characterized low\u2010grade serous ovarian cancer cell lines","volume":"6","author":"Fernandez ML","year":"2016","journal-title":"Am J Cancer Res"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-024-03869-x"},{"key":"e_1_2_8_21_1","unstructured":"BaoSC MizikovskyD PishasK et al.A robust unsupervised clustering approach for high\u2010dimensional biological imaging data reveals shared drug\u2010induced morphological signatures.bioRxiv2024; 2024.09.05.611300. [Not peer reviewed]."},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2015.09.001"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2022.01.004"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac413"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btad547"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt599"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1071"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0000000000001043"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00742-4"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac963"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2019.12.003"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.09.015"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.06.004"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2020.04.07"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10868"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02175-9"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e318290868f"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11413"},{"key":"e_1_2_8_42_1","article-title":"Epidermal growth factor receptor (EGFR) inhibitors for metastatic colorectal cancer","volume":"6","author":"Chan DLH","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01977"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.23627"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad976"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad751"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2024.155714"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.70075","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.70075","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.70075","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:31:11Z","timestamp":1783474271000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.70075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":46,"journal-issue":{"issue":"4-5","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/path.70075"],"URL":"https:\/\/doi.org\/10.1002\/path.70075","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]},"assertion":[{"value":"2025-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}