{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:23:20Z","timestamp":1790270600045,"version":"4.1.0"},"reference-count":38,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD105800"],"award-info":[{"award-number":["R01HD105800"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD096057"],"award-info":[{"award-number":["HD096057"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD110038"],"award-info":[{"award-number":["R01HD110038"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["NGP10125"],"award-info":[{"award-number":["NGP10125"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008527","name":"Dan L. Duncan Cancer Center","doi-asserted-by":"publisher","award":["CA125123"],"award-info":[{"award-number":["CA125123"]}],"id":[{"id":"10.13039\/100008527","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005332","name":"Alpha Omega Alpha","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005332","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Endometriosis is a common and debilitating disease, affecting \u223c170 million women worldwide. Affected patients have limited therapeutic options such as hormonal suppression or surgical excision of the lesions, though therapies are often not completely curative. Targeting receptor tyrosine kinases (RTKs) could provide a nonhormonal treatment option for endometriosis. We determined that 2 RTKs, macrophage-colony stimulating factor 1 receptor (CSF1R) and mast\/stem cell growth factor receptor KIT (KIT), are overexpressed in endometriotic lesions and could be novel nonhormonal therapeutic targets for endometriosis. The kinase activity of CSF1R and KIT is suppressed by pexidartinib, a small molecule inhibitor that was recently approved by the US Food and Drug Administration. Using immunohistochemistry, we detected CSF1R and KIT in endometriotic tissues obtained from peritoneal lesions, colorectal lesions, and endometriomas. Specifically, we show that KIT is localized to the epithelium of the lesions, while CSF1R is expressed in the stroma and macrophages of the endometriotic lesions. Given the high epithelial expression of CSF1R and KIT, 12Z endometriotic epithelial cells were used to evaluate the efficacy of dual CSF1R and KIT inhibition with pexidartinib. We found that pexidartinib suppressed activation in 12Z cells of JNK, STAT3, and AKT signaling pathways, which control key proinflammatory and survival networks within the cell. Using quantitative real-time polymerase chain reaction, we determined that pexidartinib suppressed interleukin 8 (IL8) and cyclin D1 (CCND1) expression. Lastly, we demonstrated that pexidartinib decreased cell growth and viability. Overall, these results indicate that pexidartinib-mediated CSF1R and KIT inhibition reduces proinflammatory signaling and cell viability in endometriosis.<\/jats:p>","DOI":"10.1210\/endocr\/bqae003","type":"journal-article","created":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T16:37:29Z","timestamp":1705250249000},"source":"Crossref","is-referenced-by-count":11,"title":["Inhibition of CSF1R and KIT With Pexidartinib Reduces Inflammatory Signaling and Cell Viability in Endometriosis"],"prefix":"10.1210","volume":"165","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6453-1648","authenticated-orcid":false,"given":"Timothy N","family":"Dunn","sequence":"first","affiliation":[{"name":"Division of Reproductive Endocrinology & Infertility, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Department of Obstetrics and Gynecology, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Department of Pathology & Immunology, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Center for Drug Discovery, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique I","family":"Cope","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Center for Drug Discovery, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suni","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Center for Drug Discovery, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tirupataiah","family":"Sirupangi","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Center for Drug Discovery, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney E","family":"Parks","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Center for Drug Discovery, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zian","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Center for Drug Discovery, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad J","family":"Creighton","sequence":"additional","affiliation":[{"name":"Dan L. Duncan Comprehensive Cancer Center Division of Biostatistics, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Human Genome Sequencing Center, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Department of Medicine at Baylor College of Medicine, Baylor College of Medicine , Houston, TX, 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramya P","family":"Masand","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]},{"name":"Department of Pathology & Immunology, Baylor College of Medicine , Houston, TX 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Alpuing Radilla","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine , Houston, TX 77030 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