Molecular Insights in Endometrial Stromal Sarcomas: Exploring New Targets for Novel Therapeutic Approaches

Uterine mesenchymal tumors (UMTs) are the second most common type of tumors within the uterus corpus after endometrial carcinomas. Among the UMTs, smooth muscle neoplasms are the most common subtype, followed by endometrial stromal sarcoma (ESS). ESSs are uncommon malignancies characterized by molecular heterogeneity and an aggressive behavior. Their management poses significant challenges, particularly for high-grade subtypes. Surgery is the primary intervention for localized disease, while the role of adjuvant therapies, including radiation and chemotherapy, must be better investigated. Hormonal therapy has shown efficacy in low-grade cases but limited success in high-grade tumors. Recent advancements in molecular profiling have revealed potential targets, offering promise for personalized treatments. However, novel therapeutic strategies are urgently needed to improve patient outcomes, particularly for advanced and recurrent disease. This review offers a perspective on the possible novel therapeutic approaches based on the most recent molecular analyses performed on endometrial stromal sarcomas.