{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:15:40Z","timestamp":1789730140545,"version":"4.0.1"},"reference-count":64,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ruth N. White Research Fellowship in Gynecologic Oncology","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Saltonstall Research Fund","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Potter Research Fund","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Sperling Family Fund Fellowship","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Bach Underwood Fund","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Robert and Deborah First Family Fund","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"DOI":"10.13039\/100006800","name":"Honorable Tina Brozman Foundation","doi-asserted-by":"publisher","award":["Rising Stars Award"],"award-info":[{"award-number":["Rising Stars Award"]}],"id":[{"id":"10.13039\/100006800","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Abnormal ion channel expression distinguishes several types of carcinoma. Here, we explore the relationship between voltage-gated sodium channels (VGSC) and epithelial ovarian cancer (EOC). We find that EOC cell lines express most VGSC, but at lower levels than fallopian tube secretory epithelial cells (the cells of origin for most EOC) or control fibroblasts. Among patient tumor samples, lower SCN8A expression was associated with improved overall survival (OS) (median 111 vs. 52 months; HR 2.04 95% CI: 1.21\u20133.44; p = 0.007), while lower SCN1B expression was associated with poorer OS (median 45 vs. 56 months; HR 0.69 95% CI 0.54\u20130.87; p = 0.002). VGSC blockade using either anti-epileptic drugs or local anesthetics (LA) decreased the proliferation of cancer cells. LA increased cell line sensitivity to platinum and taxane chemotherapies. While lidocaine had similar additive effects with chemotherapy among EOC cells and fibroblasts, bupivacaine showed a more pronounced impact on EOC than fibroblasts when combined with either carboplatin (\u0394AUC \u221237% vs. \u221216%, p = 0.003) or paclitaxel (\u0394AUC \u221237% vs. \u221222%, p = 0.02). Together, these data suggest VGSC are prognostic biomarkers in EOC and may inform new targets for therapy.<\/jats:p>","DOI":"10.3390\/cancers13215437","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T11:47:38Z","timestamp":1635767258000},"page":"5437","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Iris S.","family":"Brummelhuis","sequence":"first","affiliation":[{"name":"Faculty of Health, Medicine, and Life Sciences, Maastricht University, 6200 MD Maastricht, The Netherlands"},{"name":"Surgical ICU Translational Research Center, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Fiascone","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Dana-Farber Cancer Institute, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen T.","family":"Hasselblatt","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyorgy","family":"Frendl","sequence":"additional","affiliation":[{"name":"Surgical ICU Translational Research Center, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-5553","authenticated-orcid":false,"given":"Kevin M.","family":"Elias","sequence":"additional","affiliation":[{"name":"Surgical ICU Translational Research Center, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Dana-Farber Cancer Institute, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. 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