{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:09:19Z","timestamp":1788786559054,"version":"build-2803163510"},"reference-count":250,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council, Taiwan","award":["NSTC 113-2314-B-303-009-MY3"],"award-info":[{"award-number":["NSTC 113-2314-B-303-009-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Endometriosis is a chronic, estrogen-dependent inflammatory condition that is marked by the growth of lesions outside the uterus, along with angiogenesis, fibrosis, immune dysregulation, and pain sensitization. There is now growing evidence that receptor tyrosine kinase (RTK) signaling networks are central to these processes, integrating proliferative, angiogenic, inflammatory, endocrine, and microenvironmental signals. This review summarizes the roles of six major RTK axes in endometriosis and evaluates their receptor-specific mechanisms, therapeutic relevance, and modulation by representative phytochemicals. An English-language literature search of PubMed was conducted with no publication date restrictions using combinations and variations of the following keywords: phytochemicals, endometriosis, EGFR, VEGFR, IGF1R, PDGFR, FGFR, MET, curcumin, resveratrol, epigallocatechin gallate (EGCG), quercetin, naringenin, berberine, apigenin, luteolin, genistein, and baicalein. Additional search terms related to receptor signaling mechanisms, downstream pathways, cellular phenotypes, and therapeutic relevance were also incorporated to ensure comprehensive coverage of the literature. The RTK signaling pathways control stromal activation, lesion survival, angiogenic support, extracellular matrix remodeling, neuroimmune sensitization, and malignant progression. Of the six RTK axes examined, EGFR, VEGFR, and IGF1R have the strongest mechanistic and pharmacological support, whereas PDGFR, FGFR, and MET remain biologically plausible targets. Even though phytochemicals do not consistently act as receptor-selective RTK inhibitors, evidence shows they reduce RTK-centred signaling networks by targeting common downstream hubs. As a result of their effects at the network level, the phytochemicals may help to suppress lesion proliferation, angiogenesis, invasion, fibrosis, inflammation, oxidative stress, and pain sensitization. Endometriosis should be viewed as an RTK-centered network disease rather than a single-pathway disorder. In this context, phytochemicals act as modulators that attenuate signaling hubs, offering a mechanistically aligned strategy for a disease driven by redundancy and microenvironmental crosstalk.<\/jats:p>","DOI":"10.3390\/ph19091413","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"1413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phytochemicals Modulating Receptor Tyrosine Kinase Signaling Networks in Endometriosis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8024-9150","authenticated-orcid":false,"given":"Che-Fang","family":"Hsu","sequence":"first","affiliation":[{"name":"Cellular Oncology Laboratory, Center for Prevention and Therapy of Gynecological Cancers, Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Feng","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, Xiamen 361023, China"},{"name":"Leadtek Biomedical, Inc., New Taipei City 235603, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-018-0008-5","article-title":"Endometriosis","volume":"4","author":"Zondervan","year":"2018","journal-title":"Nat. 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