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Status of the Current Treatment Options and Potential Future Targets in Uterine Leiomyosarcoma: A Review

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Title: Status of the Current Treatment Options and Potential Future Targets in Uterine Leiomyosarcoma: A Review
Authors: Asano, Hiroshi Browse this author
Isoe, Toshiyuki Browse this author
Ito, Yoichi M. Browse this author
Nishimoto, Naoki Browse this author →KAKEN DB
Watanabe, Yudai Browse this author
Yokoshiki, Saki Browse this author
Watari, Hidemichi Browse this author →KAKEN DB
Keywords: uterine leiomyosarcoma
next-generation sequencing
molecular-targeted drugs
PARP inhibitors
Issue Date: Mar-2022
Publisher: MDPI
Journal Title: Cancers
Volume: 14
Issue: 5
Start Page: 1180
Publisher DOI: 10.3390/cancers14051180
Abstract: Simple Summary Uterine leiomyosarcoma (uLMS) is a rare and aggressive mesenchymal malignancy. Although approximately 65% of patients are diagnosed in stage I, more than 50% have relapsed disease, and effective therapies for recurrent and advanced cases are limited. This review summarizes the current standard therapies for uLMS and the molecular properties of uLMS and describes the status of promising novel molecular-targeted therapies. Uterine leiomyosarcoma (uLMS) is the most common subtype of mesenchymal tumors in the uterus. This review aims to summarize the current standard therapies and the molecular properties of uLMS for novel molecular-targeted therapies. Although 65% of uLMS cases are diagnosed in stage I, the 5-year overall survival rate is less than 60%. The only effective treatment for uLMS is complete and early resection, and chemotherapy is the main treatment for unresectable advanced or recurrent cases. No chemotherapy regimen has surpassed doxorubicin monotherapy as the first-line chemotherapy for unresectable advanced or recurrent cases in terms of overall survival in phase 3 trials. As a second-line treatment, pazopanib, trabectedin, and eribulin are used, but their therapeutic effects are not sufficient, highlighting the urgent need for development of novel treatments. Recent developments in gene analysis have revealed that homologous recombination deficiency (HRD), including breast cancer susceptibility gene 2 (BRCA2) mutations, are frequently observed in uLMS. In preclinical studies and several case series, poly(adenosine diphosphate-ribose)polymerase inhibitors showed antitumor effects on uLMS cell lines with BRCA2 mutations or HRD and in recurrent or persistent cases of uLMS with BRCA2 mutations. Thus, HRD, including BRCA mutations, may be the most promising therapeutic target for uLMS.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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