Status of the Current Treatment Options and Potential Future Targets in Uterine Leiomyosarcoma: A Review
by
,
Hiroshi Asano
1
,
Toshiyuki Isoe
2,
Yoichi M. Ito
3,
Naoki Nishimoto
3,
Yudai Watanabe
2,
Saki Yokoshiki
2 and
Hidemichi Watari
1,* 
1
Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
2
Clinical Research and Medical Innovation Center, Promotion Unit, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo 060-8648, Japan
3
Data Science Center, Promotion Unit, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo 060-8648, Japan
*
Author to whom correspondence should be addressed.
Cancers 2022, 14(5), 1180; https://doi.org/10.3390/cancers14051180
Submission received: 20 December 2021
/
Revised: 11 February 2022
/
Accepted: 22 February 2022
/
Published: 24 February 2022
(This article belongs to the Special Issue New Directions for Treating Soft Tissue Sarcomas)
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.
Abstract
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.
