{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:54:15Z","timestamp":1792079655599,"version":"4.4.0"},"reference-count":230,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["HD106285"],"award-info":[{"award-number":["HD106285"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Uterine leiomyosarcoma (uLMS) is the most common subtype of uterine sarcomas. They have a poor prognosis with high rates of recurrence and metastasis. The five-year survival for uLMS patients is between 25 and 76%, with survival rates approaching 10\u201315% for patients with metastatic disease at the initial diagnosis. Accumulating evidence suggests that several biological pathways are involved in uLMS pathogenesis. Notably, drugs that block abnormal functions of these pathways remarkably improve survival in uLMS patients. However, due to chemotherapy resistance, there remains a need for novel drugs that can target these pathways effectively. In this review article, we provide an overview of the recent progress in ascertaining the biological functions and regulatory mechanisms in uLMS from the perspective of aberrant biological pathways, including DNA repair, immune checkpoint blockade, protein kinase and intracellular signaling pathways, and the hedgehog pathway. We review the emerging role of epigenetics and epitranscriptome in the pathogenesis of uLMS. In addition, we discuss serum markers, artificial intelligence (AI) combined with machine learning, shear wave elastography, current management and medical treatment options, and ongoing clinical trials for patients with uLMS. Comprehensive, integrated, and deeper insights into the pathobiology and underlying molecular mechanisms of uLMS will help develop novel strategies to treat patients with this aggressive tumor.<\/jats:p>","DOI":"10.3390\/cells13131106","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T07:20:06Z","timestamp":1719386406000},"page":"1106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-8946","authenticated-orcid":false,"given":"Qiwei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obianuju Sandra","family":"Madueke-Laveaux","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Cun","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1545-2547","authenticated-orcid":false,"given":"Marta","family":"Wlodarczyk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Garcia","sequence":"additional","affiliation":[{"name":"Greehey Children\u2019s Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX 78229, USA"},{"name":"Department of Cell Systems and Anatomy, University of Texas Health Science Center, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7295-678X","authenticated-orcid":false,"given":"Katia Candido","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento deObstetricia e Ginecologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8778-4447","authenticated-orcid":false,"given":"Ayman","family":"Al-Hendy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Reichert, V.M.C., Alwafai, Z., Zygmunt, M.T., Vollmer, M., and K\u00f6hler, G. 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