Uterine Leiomyosarcoma

These cases expand the landscape of FOXO1-rearranged neoplasms and describe a potential new uterine mesenchymal entity. Further study of additional cases is needed to establish whether these rearrangements truly represent an initiating event for a distinct subset of uterine sarcomas, or whether FOXO1 rearrangements simply represent an additional noninitiating/nondriver event within other established tumor types.

The integration of checkpoint inhibitors with targeted immunomodulation and personalized therapeutic approaches may improve treatment efficacy. Future research should focus on refining patient selection criteria, enhancing macrophage-targeted therapies, and optimizing immune profiling techniques to maximize therapeutic outcomes for uterine leiomyosarcoma.

Although trabectedin-olaparib combination reached the prespecified threshold for statistical significance for PFS (p<0.10), the benefit was marginal in the all-comers STS population. Nonetheless, patients affected by PARP1-expressing STS and uterine leiomyosarcoma derived substantial benefit from the combination, supporting further histology- and biomarker-driven investigation in these settings.

P2, N=23, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Nov 2026

ATRX status may serve as a potential biomarker for prognosis and therapeutic stratification. Future clinical trials investigating epigenetic therapies could offer novel treatment strategies for ATRX-deficient sarcomas.

In cancer treatment, contrast-enhanced MRI is useful for identifying the size and location of tumor masses. However, contrast-enhanced MRI does not lead to the diagnosis of tumor masses. Therefore, early blood tests and tumor biopsy results are important for differential diagnosis and early treatment decisions.

Emerging therapeutic approaches aim to restore the tumor-suppressive miRNAs or inhibit oncogenic ones using mimics or antagomiRs. Overall miRNAs represent critical regulators of uLMS pathogenesis and hold significant potential for precision diagnosis, prognostication, and targeted therapy, though larger validation studies and improved delivery systems are required before clinical translation.

P2, N=17, Active, not recruiting, Stanford University | Recruiting --> Active, not recruiting | N=25 --> 17 | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Dec 2025 --> May 2026

Accurate recognition of IMT with unusual features is crucial for targeted treatment. ALK protein expression and molecular testing play critical roles in diagnosis and differential diagnosis, and lowering the detection threshold to improve sensitivity is urgently needed.

Our results reveal molecular heterogeneity in uterine leiomyosarcomas and provide potential diagnostic and prognostic biomarkers for improved patient management.

Molecular profiling of uLMS has also uncovered possible therapeutic targets in the most common type of uterine sarcoma, where prognostication and clinical management remain challenging. This review discusses the current histologic and molecular classification of low- and high-grade ESS, FUS, and conventional and variant uLMS and explores the potential impact of the genetic alterations observed in these uterine sarcomas on treatment.

Primary uLMS and subsequent recurrences display genomic intra-individual concordance, with sustained driver cancer gene alterations over time. Chromosomal instability was higher in recurrent tumors.