{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:22:07Z","timestamp":1791400927842,"version":"4.3.3"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Desmoid tumors (DTs) are rare, fibroblastic neoplasms characterized by locally aggressive behavior, unpredictable clinical trajectories, and a substantial impact on patient quality of life despite minimal metastatic potential. Although the underlying biology of DTs remains incompletely defined, associations with prior trauma, hormonal exposure, and aberrant Wnt\/\u03b2-catenin signaling\u2014including somatic CTNNB1 mutations and germline APC alterations seen in Familial Adenomatous Polyposis\u2014have informed both historical and contemporary therapeutic approaches. Management strategies have evolved from surgery-dominant paradigms toward individualized, multimodal treatment algorithms emphasizing systemic medical therapy, as reflected in current NCCN and Desmoid Tumor Working Group recommendations. This review focuses on the medical management of DTs, tracing the evolution from earlier noncytotoxic therapies, including antiestrogen agents such as tamoxifen, to modern systemic options supported by prospective and randomized data. We summarize available evidence for four principal classes of medical therapy: nonsteroidal anti-inflammatory drugs, cytotoxic chemotherapy (with particular emphasis on anthracycline-based regimens), tyrosine kinase inhibitors\u2014most notably sorafenib\u2014and the emerging class of \u03b3-secretase inhibitors. Recent phase III data supporting the efficacy of nirogacestat highlight a shift toward mechanism-based, targeted treatment with demonstrable benefits in progression-free survival, symptom control, and patient-reported outcomes. Collectively, these advances underscore a maturing therapeutic landscape in which systemic therapy plays a central role in disease control, symptom palliation, and preservation of function for patients with advanced desmoid tumors.<\/jats:p>","DOI":"10.3390\/cancers18101521","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T12:05:22Z","timestamp":1778501122000},"page":"1521","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Systemic Therapies for Desmoid Tumors: A Review of Past, Present, and Future Treatments"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7208-1266","authenticated-orcid":false,"given":"Skylar L.","family":"Nahi","sequence":"first","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Dann","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1007\/s12325-023-02592-0","article-title":"Desmoid tumors: A comprehensive review","volume":"40","author":"Bektas","year":"2023","journal-title":"Adv. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.hoc.2013.07.008","article-title":"Desmoid tumors: A comprehensive review of the evolving biology, unpredictable behavior, and myriad of management options","volume":"27","author":"Devata","year":"2013","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102114","DOI":"10.1016\/j.canep.2022.102114","article-title":"The epidemiology of desmoid tumors in Denmark","volume":"77","author":"Anneberg","year":"2022","journal-title":"Cancer Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"815","DOI":"10.6004\/jnccn.2022.0035","article-title":"Soft tissue sarcoma, version 2.2022, nccn clinical practice guidelines in oncology","volume":"20","author":"Kane","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_5","unstructured":"The Desmoid Tumor Working Group (2020). The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients. Eur. J. Cancer, 127, 96\u2013107."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1001\/jamaoncol.2024.1805","article-title":"Current management of desmoid tumors: A review","volume":"10","author":"Kasper","year":"2024","journal-title":"JAMA Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100578","DOI":"10.1016\/j.esmoop.2022.100578","article-title":"Association between recent pregnancy or hormonal contraceptive exposure and outcome of desmoid-type fibromatosis","volume":"7","author":"Debaudringhien","year":"2022","journal-title":"ESMO Open"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/0002-9610(86)90076-0","article-title":"The desmoid syndrome. New aspects in the cause, pathogenesis and treatment of the desmoid tumor","volume":"151","author":"Reitamo","year":"1986","journal-title":"Am. J. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1002\/cncr.21553","article-title":"Estrogen receptor-beta expression in extraabdominal fibromatoses: An analysis of 40 cases","volume":"106","author":"Deyrup","year":"2006","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e388","DOI":"10.1111\/j.1463-1318.2011.02758.x","article-title":"Anti-oestrogen therapy in the treatment of desmoid tumours: A systematic review","volume":"13","author":"Bocale","year":"2011","journal-title":"Colorectal Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/cncr.11937","article-title":"High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors","volume":"100","author":"Hansmann","year":"2004","journal-title":"Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10689-015-9830-z","article-title":"Long-term outcome of sporadic and FAP-associated desmoid tumors treated with high-dose selective estrogen receptor modulators and sulindac: A single-center long-term observational study in 134 patients","volume":"15","author":"Quast","year":"2016","journal-title":"Fam. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/pbc.24457","article-title":"Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: Results of a children\u2019s oncology group (cog) phase ii study","volume":"60","author":"Skapek","year":"2013","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1002\/cncr.34332","article-title":"Evolving strategies for management of desmoid tumor","volume":"128","author":"Riedel","year":"2022","journal-title":"Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1111\/cas.12037","article-title":"Signal transduction pathway analysis in desmoid-type fibromatosis: Transforming growth factor-beta, COX2 and sex steroid receptors","volume":"103","author":"Mignemi","year":"2012","journal-title":"Cancer Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1097\/SLA.0000000000005415","article-title":"A nationwide prospective clinical trial on active surveillance in patients with non-intraabdominal desmoid-type fibromatosis: The grafiti trial","volume":"277","author":"Schut","year":"2023","journal-title":"Ann. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1158\/1078-0432.CCR-24-2340","article-title":"Active surveillance in patients with extra-abdominal desmoid-type fibromatosis: A pooled analysis of three prospective observational studies","volume":"31","author":"Colombo","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ejca.2020.06.022","article-title":"Active surveillance in desmoid-type fibromatosis: A systematic literature review","volume":"137","author":"Timbergen","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1158\/1078-0432.CCR-21-4205","article-title":"A prospective observational study of active surveillance in primary desmoid fibromatosis","volume":"28","author":"Colombo","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/BF02053335","article-title":"Noncytotoxic drug therapy for intra-abdominal desmoid tumor in patients with familial adenomatous polyposis","volume":"35","author":"Tsukada","year":"1992","journal-title":"Dis. Colon. Rectum"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.1200\/JCO.2009.25.5950","article-title":"Successful treatment with meloxicam, a cyclooxygenase-2 inhibitor, of patients with extra-abdominal desmoid tumors: A pilot study","volume":"28","author":"Nishida","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hamada, S., Futamura, N., Ikuta, K., Urakawa, H., Kozawa, E., Ishiguro, N., and Nishida, Y. (2014). CTNNB1 S45F mutation predicts poor efficacy of meloxicam treatment for desmoid tumors: A pilot study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096391"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1200\/JCO.2006.08.2966","article-title":"Vinblastine and methotrexate for desmoid fibromatosis in children: Results of a Pediatric Oncology Group Phase II Trial","volume":"25","author":"Skapek","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s12306-022-00738-x","article-title":"Clinical outcomes of medical treatments for progressive desmoid tumors following active surveillance: A systematic review","volume":"107","author":"Tsukamoto","year":"2023","journal-title":"Musculoskelet. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1002\/1097-0142(19931201)72:11<3244::AID-CNCR2820721118>3.0.CO;2-D","article-title":"Combination chemotherapy in adult desmoid tumors","volume":"72","author":"Patel","year":"1993","journal-title":"Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1200\/JCO.2005.02.1923","article-title":"Successful chemotherapeutic modality of doxorubicin plus dacarbazine for the treatment of desmoid tumors in association with familial adenomatous polyposis","volume":"24","author":"Gega","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1016\/j.ejca.2009.08.016","article-title":"Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis","volume":"45","author":"Constantinidou","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/1097-0142(20010901)92:5<1259::AID-CNCR1446>3.0.CO;2-Y","article-title":"Low-dose chemotherapy with methotrexate and vinblastine for patients with advanced aggressive fibromatosis","volume":"92","author":"Azzarelli","year":"2001","journal-title":"Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/annonc\/mdr051","article-title":"Chemotherapy in patients with desmoid tumors: A study from the French Sarcoma Group (FSG)","volume":"23","author":"Garbay","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e110632","DOI":"10.15252\/embj.2022110632","article-title":"Topoisomerase II poisons inhibit vertebrate DNA replication through distinct mechanisms","volume":"41","author":"Mehta","year":"2022","journal-title":"EMBO J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1002\/cncr.25089","article-title":"Clinical outcomes of systemic therapy for patients with deep fibromatosis (desmoid tumor)","volume":"116","author":"Keohan","year":"2010","journal-title":"Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"114119","DOI":"10.1016\/j.ejca.2024.114119","article-title":"Real-word experience of pazopanib and sorafenib in patients with desmoid tumors: A CanSaRCC multi-center study","volume":"205","author":"Noujaim","year":"2024","journal-title":"Eur. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.1158\/1078-0432.CCR-10-3322","article-title":"Activity of Sorafenib against desmoid tumor\/deep fibromatosis","volume":"17","author":"Gounder","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1056\/NEJMoa1805052","article-title":"Sorafenib for advanced and refractory desmoid tumors","volume":"379","author":"Gounder","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1200\/JCO.2005.04.0717","article-title":"Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor)","volume":"24","author":"Heinrich","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4884","DOI":"10.1158\/1078-0432.CCR-10-1177","article-title":"Efficacy of imatinib in aggressive fibromatosis: Results of a phase II multicenter Sarcoma Alliance for Research through Collaboration (SARC) trial","volume":"16","author":"Chugh","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/annonc\/mdq341","article-title":"Imatinib for progressive and recurrent aggressive fibromatosis (desmoid tumors): An FNCLCC\/French Sarcoma Group phase II trial with a long-term follow-up","volume":"22","author":"Penel","year":"2011","journal-title":"Ann. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10637-013-0059-0","article-title":"A prospective multicenter phase II study of sunitinib in patients with advanced aggressive fibromatosis","volume":"32","author":"Jo","year":"2014","journal-title":"Invest. New Drugs"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ejca.2017.02.001","article-title":"Imatinib induces sustained progression arrest in RECIST progressive desmoid tumours: Final results of a phase II study of the German Interdisciplinary Sarcoma Group (GISG)","volume":"76","author":"Kasper","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S1470-2045(19)30276-1","article-title":"Pazopanib or methotrexate-vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): A non-comparative, randomised, open-label, multicentre, phase 2 study","volume":"20","author":"Toulmonde","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1056\/NEJMoa2210140","article-title":"Nirogacestat, a gamma-secretase inhibitor for desmoid tumors","volume":"388","author":"Gounder","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S1051","DOI":"10.1016\/j.annonc.2024.08.1857","article-title":"1766P Updated results of the RINGSIDE phase II trial and open-label extension of AL102 for treatment of desmoid tumors","volume":"35","author":"Kasper","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4088","DOI":"10.1002\/cncr.29564","article-title":"Targeting the Notch pathway: A potential therapeutic approach for desmoid tumors","volume":"121","author":"Shang","year":"2015","journal-title":"Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1002\/cncr.29562","article-title":"Notch inhibition in desmoids: \u201cSure it works in practice, but does it work in theory?\u201d","volume":"121","author":"Gounder","year":"2015","journal-title":"Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Braggio, D.A., Costas, C.d.F.F., Koller, D., Jin, F., Zewdu, A., Lopez, G., Batte, K., Casadei, L., Welliver, M., and Horrigan, S.K. (2022). Preclinical efficacy of the Wnt\/beta-catenin pathway inhibitor BC2059 for the treatment of desmoid tumors. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0276047"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11523","DOI":"10.1200\/JCO.2022.40.16_suppl.11523","article-title":"Results of a phase I dose escalation and expansion study of tegavivint (BC2059), a first-in-class TBL1 inhibitor for patients with progressive, unresectable desmoid tumor","volume":"40","author":"Cranmer","year":"2022","journal-title":"J. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/10\/1521\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T12:22:03Z","timestamp":1778502123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/10\/1521"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,9]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cancers18101521"],"URL":"https:\/\/doi.org\/10.3390\/cancers18101521","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,9]]}}}