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We recently discovered that zafirlukast, an FDA\u2010approved medication for asthma, is a pan\u2010thiol isomerase inhibitor. Zafirlukast inhibited the growth of multiple cancer cell lines with an IC\n                    <jats:sub>50<\/jats:sub>\n                    in the low micromolar range, while also inhibiting cellular thiol isomerase activity, EGFR activation, and downstream phosphorylation of Gab1. Zafirlukast also blocked the procoagulant activity of OVCAR8 cells by inhibiting tissue factor\u2010dependent Factor Xa generation. In an ovarian cancer xenograft model, statistically significant differences in tumor size between control vs treated groups were observed by Day 18. Zafirlukast also significantly reduced the number and size of metastatic tumors found within the lungs of the mock\u2010treated controls. When added to a chemotherapeutic regimen, zafirlukast significantly reduced growth, by 38% compared with the mice receiving only the chemotherapeutic treatment, and by 83% over untreated controls. Finally, we conducted a pilot clinical trial in women with tumor marker\u2010only (CA\u2010125) relapsed ovarian cancer, where the rate of rise of CA\u2010125 was significantly reduced following treatment with zafirlukast, while no severe adverse events were reported. Thiol isomerase inhibition with zafirlukast represents a novel, well\u2010tolerated therapeutic in the treatment of ovarian cancer.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201952r","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T12:50:23Z","timestamp":1681303823000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Targeting thiol isomerase activity with zafirlukast to treat ovarian cancer from the bench to clinic"],"prefix":"10.1096","volume":"37","author":[{"given":"Justine A.","family":"Gelzinis","sequence":"first","affiliation":[{"name":"College of Pharmacy and Health Sciences Western New England University  Springfield Massachusetts USA"},{"name":"Institute for Cardiovascular &amp; Metabolic Research, School of Biological Sciences University of Reading  Reading UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie K.","family":"Szahaj","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Health Sciences Western New England University  Springfield Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roelof H.","family":"Bekendam","sequence":"additional","affiliation":[{"name":"Division of Hemostasis and Thrombosis, Department of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sienna E.","family":"Wurl","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Health Sciences Western New England University  Springfield Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan M.","family":"Pantos","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Health Sciences Western New England University  Springfield Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina A.","family":"Verbetsky","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Health Sciences Western New England University  Springfield Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Dufresne","sequence":"additional","affiliation":[{"name":"Baystate Research Facility Baystate Medical Center, UMass Chan Medical School  Springfield Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Shea","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlind C.","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy University of Kentucky  789 S. 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