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Sarcoma
Volume 2015 (2015), Article ID 243298, 14 pages
http://dx.doi.org/10.1155/2015/243298
Review Article

Potential Therapeutic Targets in Uterine Sarcomas

1Department of Oncology, Gynaecologic Oncology, KU Leuven (University of Leuven), 3000 Leuven, Belgium
2Department of Obstetrics and Gynaecology, University Hospitals Leuven, 3000 Leuven, Belgium
3Center for Gynaecologic Oncology Amsterdam (CGOA), Antoni van Leeuwenhoek-Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands

Received 14 August 2015; Accepted 30 September 2015

Academic Editor: Silvia Stacchiotti

Copyright © 2015 Tine Cuppens et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Uterine sarcomas are rare tumors accounting for 3,4% of all uterine cancers. Even after radical hysterectomy, most patients relapse or present with distant metastases. The very limited clinical benefit of adjuvant cytotoxic treatments is reflected by high mortality rates, emphasizing the need for new treatment strategies. This review summarizes rising potential targets in four distinct subtypes of uterine sarcomas: leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Based on clinical reports, promising approaches for uterine leiomyosarcoma patients include inhibition of VEGF and mTOR signaling, preferably in combination with other targeted or cytotoxic compounds. Currently, the only targeted therapy approved in leiomyosarcoma patients is pazopanib, a multitargeted inhibitor blocking VEGFR, PDGFR, FGFR, and c-KIT. Additionally, preclinical evidence suggests effect of the inhibition of histone deacetylases, tyrosine kinase receptors, and the mitotic checkpoint protein aurora kinase A. In low-grade endometrial stromal sarcomas, antihormonal therapies including aromatase inhibitors and progestins have proven activity. Other potential targets are PDGFR, VEGFR, and histone deacetylases. In high-grade ESS that carry the YWHAE/FAM22A/B fusion gene, the generated 14-3-3 oncoprotein is a putative target, next to c-KIT and the Wnt pathway. The observation of heterogeneity within uterine sarcoma subtypes warrants a personalized treatment approach.