{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:52:46Z","timestamp":1791363166639,"version":"4.3.1"},"reference-count":51,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Desmoid-type fibromatosis, also known as desmoid tumor (DT), is a rare and locally aggressive soft tissue neoplasm driven by constitutive activation of the Wnt\/\u03b2-catenin signaling pathway, most commonly through CTNNB1 or APC alterations. While some tumors progress and cause substantial morbidity, approximately 25\u201338% undergo spontaneous regression during active surveillance, which is currently recommended as the first-line management strategy. Although advances in next-generation sequencing and transcriptomic profiling have elucidated the molecular drivers of tumor progression, the molecular mechanisms underlying spontaneous regression remain poorly understood. This review summarizes current knowledge of the molecular pathogenesis of DT and proposed mechanisms of spontaneous regression, including attenuation of Wnt\/\u03b2-catenin signaling, hormonal modulation, alterations in the immune microenvironment, and crosstalk between Wnt signaling and other pathways such as Notch, PDGFR\/c-Abl\/HIF1\u03b1, and TGF-\u03b2. Based on the current knowledge of the molecular mechanisms in DT, spontaneous regression appears to reflect a multifactorial transition from an active proliferative state toward a quiescent, fibrotic phenotype rather than a single molecular event. Further studies integrating single-cell and spatial transcriptomics with immune profiling are warranted to identify therapeutic targets and stratify patients for active surveillance versus active treatment.<\/jats:p>","DOI":"10.3390\/ijms27198887","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:28:57Z","timestamp":1791361737000},"page":"8887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Mechanisms Underlying Progression and Spontaneous Regression in Desmoid Tumors"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5962-8287","authenticated-orcid":false,"given":"Shinji","family":"Miwa","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiro","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7489-1657","authenticated-orcid":false,"given":"Takashi","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Yonezawa","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei","family":"Morinaga","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Demura","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1093\/annonc\/mdx323","article-title":"An update on the management of sporadic desmoid-type fibromatosis: A European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)\/Soft Tissue and Bone Sarcoma Group (STBSG)","volume":"28","author":"Kasper","year":"2017","journal-title":"Ann. 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