Leiomyosarcoma

Our new unique mouse model will allow further studies of the effects of Trp53 nonsense mutation in a multi-organ system and serve as a model for the Li-Fraumeni syndrome (LFS). It will also be valuable for preclinical evaluation of novel therapeutic strategies for targeting TP53 nonsense mutations in cancer.

Notably, weak DOG1 positivity was observed, a rare finding that may complicate distinction from gastrointestinal stromal tumours. This case highlights the diagnostic challenges of small bowel LMS, the central role of surgical resection in management, and the need for careful pathological evaluation to avoid misclassification and guide prognosis.

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.

This report highlights a rare, malignant craniofacial PEComa with extensive invasion into the orbit and skull base, expanding the known clinical and molecular spectrum of these tumors.

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.

P1/2, N=30, Completed, National Taiwan University Hospital | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Oct 2025

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

SDHB positivity may indicate favorable tumor biology, but further studies are needed to validate its prognostic value. Surgical resection remains curative for localized PHL.

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.

Immune profiling shows P2 as immunosuppressive, characterized by LGALS9 and M2 macrophages. Our proteogenomic analyses provide a molecular landscape of LMS, revealing biological insights, patient outcome stratification, and therapeutic targets.

Quisinostat also showed potent activity in leiomyosarcoma (LMS) cell lines (5.82-31.32 nM), which represent an additional complex karyotype soft tissue sarcoma. Quisinostat demonstrated strong preclinical activity and synergy with standard-of-care doxorubicin in models of UPS and LMS.