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Most patients are initially responsive to these treatments; however, nearly 90% will develop recurrence and inevitably succumb to chemotherapy\u2010resistant disease. Recent studies have revealed that the epigenetic modifier lysine\u2010specific histone demethylase 1A (KDM1A\/LSD1) is highly overexpressed in OCa. However, the role of KDM1A in chemoresistance and whether its inhibition enhances chemotherapy response in OCa remains uncertain. Analysis of TCGA datasets revealed that KDM1A expression is high in patients who poorly respond to chemotherapy. Western blot analysis show that treatment with chemotherapy drugs cisplatin, carboplatin, and paclitaxel increased KDM1A expression in OCa cells. KDM1A knockdown (KD) or treatment with KDM1A inhibitors NCD38 and SP2509 sensitized established and patient\u2010derived OCa cells to chemotherapy drugs in reducing cell viability and clonogenic survival and inducing apoptosis. Moreover, knockdown of KDM1A sensitized carboplatin\u2010resistant A2780\u2010CP70 cells to carboplatin treatment and paclitaxel\u2010resistant SKOV3\u2010TR cells to paclitaxel. RNA\u2010seq analysis revealed that a combination of KDM1A\u2010KD and cisplatin treatment resulted in the downregulation of genes related to epithelial\u2010mesenchymal transition (EMT). Interestingly, cisplatin treatment increased a subset of NF\u2010\u03baB pathway genes, and KDM1A\u2010KD or KDM1A inhibition reversed this effect. Importantly, KDM1A\u2010KD, in combination with cisplatin, significantly reduced tumor growth compared to a single treatment in an orthotopic intrabursal OCa xenograft model. Collectively, these findings suggest that combination of KDM1A inhibitors with chemotherapy could be a promising therapeutic approach for the treatment of OCa.<\/jats:p>","DOI":"10.1002\/mc.23792","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T09:46:41Z","timestamp":1720691201000},"page":"2026-2039","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["KDM1A\/LSD1 inhibition enhances chemotherapy response in ovarian cancer"],"prefix":"10.1002","volume":"63","author":[{"given":"Yihong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology UT Health San Antonio San Antonio Texas USA"},{"name":"Department of Neurosurgery, Xiangya Hospital Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica D.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology UT Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridharan","family":"Jayamohan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology UT Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology UT Health San Antonio San Antonio Texas USA"},{"name":"Department of Neurosurgery, Xiangya Hospital Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhakar P.","family":"Venkata","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology UT Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diksha","family":"Jamwal","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology UT Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1390-9892","authenticated-orcid":false,"given":"Salvador","family":"Alejo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology UT Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zou","sequence":"additional","affiliation":[{"name":"Greehey Children's Cancer Research Institute UT Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Lai","sequence":"additional","affiliation":[{"name":"Greehey Children's Cancer Research Institute UT Health San Antonio San Antonio Texas USA"},{"name":"Department of Molecular Medicine UT Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suryavathi","family":"Viswanadhapalli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology UT Health San Antonio San Antonio Texas USA"},{"name":"Mays Cancer Center UT Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2849-4076","authenticated-orcid":false,"given":"Ratna K.","family":"Vadlamudi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology UT Health San Antonio San Antonio Texas USA"},{"name":"Mays Cancer Center UT Health San Antonio San Antonio Texas USA"},{"name":"Audie L. 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