{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:16:33Z","timestamp":1780085793014,"version":"3.54.0"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015083","name":"Peking University People's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015083","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chemoresistance is a key contributor of ovarian cancer (OC) mortality. Clinical observations of extended survival in OC patients with rheumatic comorbidities following anti-rheumatic treatment suggest hydroxychloroquine (HCQ) and sulfasalazine (SSZ) could act as chemosensitizers. However, how the HCQ\/SSZ combination counteracts platinum\u2013taxane resistance remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A multiomics strategy was applied, integrating transcriptomics from resistant and sensitive OC models with network pharmacology, consensus clustering, machine learning, and molecular docking, which indicated potential binding to predicted targets (e.g., SSZ\u2013tumor necrosis factor (TNF): \u22126.99 kcal\/mol). Validation included\n                      <jats:italic>in vitro<\/jats:italic>\n                      drug sensitivity assays and clinical cytokine profiling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis identified 26 overlapping genes as shared targets and classified patients into chemoresistant (Subtype 1) and chemosensitive (Subtype 2) subgroups, with Subtype 1 associated with protumorigenic pathway enrichment, immunosuppressive features, and poorer prognosis. A seven-hub-gene predictive signature was established. HCQ\/SSZ appeared to remodel the inflammatory\u2013immune tumor microenvironment, primarily through cytokine and nuclear factor kappa B (NF-\u03baB) signaling. Clinical cytokine data supported a localized immunosuppressive niche, and\n                      <jats:italic>in vitro<\/jats:italic>\n                      evidence confirmed cytotoxic effects. Patients receiving long-term HCQ\/SSZ therapy generally showed improved clinical outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study suggests that HCQ\/SSZ may reverse chemoresistance by reprogramming the inflammatory\u2013immune microenvironment, offering a molecular rationale for further investigation into their repurposing as chemosensitizers and maintenance therapies in OC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1790210","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T06:34:30Z","timestamp":1774506870000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Reversing chemoresistance in ovarian cancer: network pharmacology reveals how hydroxychloroquine\/sulfasalazine duotherapy remodels tumor inflammatory\u2013immune microenvironment"],"prefix":"10.3389","volume":"17","author":[{"given":"Xin","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital","place":["Beijing, China"]},{"name":"Department of Clinical Medicine, Peking University Health Science Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital","place":["Beijing, China"]},{"name":"Department of Clinical Medicine, Peking University Health Science Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Peking University School and Hospital of Stomatology and National Center for Stomatology and National Clinical Research Center for Oral Disease and National Engineering Research Center of Oral Biomaterials and Digital Medical Devices","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital","place":["Beijing, China"]},{"name":"Department of Clinical Medicine, Peking University Health Science Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University People\u2019s Hospital","place":["Beijing, China"]},{"name":"Department of Clinical Medicine, Peking University Health Science Center","place":["Beijing, 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