Leiomyosarcoma

P2, N=30, Recruiting, Dana-Farber Cancer Institute | Not yet recruiting --> Recruiting

ATRX mutational 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.

This study demonstrates evidence for EBV particle exposure to influence microglial immune phenotypes by suppressing IFN production, providing a putative mechanism for EBV virion expression in the CNS to suppress anti-tumoral immunity against EBV+ cancers. These results are particularly relevant to the etiology of EBV+ primary CNS cancers in immunocompromised people, where microglial play a heightened role in protecting the CNS in the absence of adaptive immunity.

P2, N=28, Recruiting, Instituto do Cancer do Estado de São Paulo | Active, not recruiting --> Recruiting

Postoperatively, she was treated with an Ewing sarcoma‑based chemotherapy protocol (vincristine, doxorubicin, cyclophosphamide/ifosfamide and etoposide (VDC/IE)), but unfortunately, she died 10 months after surgery. While on one hand, among adolescents, fertility preservation poses an additional ethical and therapeutic challenge, on the other hand, rapid, individualised decision‑making is also required to prevent clinical deterioration. This case highlights the diagnostic and therapeutic dilemmas faced, the need to consider PNET in the differential diagnosis of aggressive uterine masses even in adolescents, the important role of ancillary testing like IHC and molecular studies for a definitive diagnosis and the difficulties in balancing life‑saving surgery and fertility preservation when disease is advanced.

P2, N=20, Recruiting, Memorial Sloan Kettering Cancer Center

P1/2, N=107, Recruiting, STORM Therapeutics LTD | N=188 --> 107 | Trial completion date: Jun 2027 --> Jun 2028 | Trial primary completion date: Dec 2026 --> Dec 2027

In cultured LMS cells, proliferation correlated with increased nuclear smoothelin positivity. These findings suggest that smoothelin is linked to proliferative capacity in SMTs, and its altered subcellular distribution may have potential utility in the pathological evaluation of SMTs.

Finally, autophagy-related analyses demonstrated increased LC3B-II levels accompanied by p62 accumulation, suggesting altered autophagic processing rather than simple activation of autophagy. Collectively, these findings demonstrate that bortezomib exerts cytotoxic effects in Ut-LMS cells through coordinated regulation of proteasome inhibition-associated apoptosis, cell cycle control, mitochondrial dysfunction, and autophagy-related signaling, with cell line-specific differences in stress response pathways.

Liquid biopsy holds promise for improving uLMS diagnosis and management. However, standardization and biomarker validation remain essential to achieve reliable clinical translation and enable earlier, more precise treatment strategies.

In this study, targeted next-generation sequencing using the AmpliSeq for Illumina Cancer HotSpot Panel identified pathogenic mutations in canonical cancer driver genes: tumor protein p53 (TP53) NM_000546.6:c.730G>T (p.Gly244Cys) and platelet-derived growth factor receptor alpha (PDGFRA) NM_006206.6:c.2525A>T (p.Asp842Val) mutations in renal leiomyosarcoma and NRAS proto-oncogene, GTPase (NRAS) NM_002524.5:c.35G>T (p.Gly12Val) mutation in the ovarian tumor. These findings suggest a potential benefit of personalized therapies for XP patients with internal malignancies.

Subgroup analysis revealed a distinct transcriptomic profile in leiomyosarcoma, while gene fusion analysis detected clinically relevant alterations. These findings demonstrate that RNA-NGS provides biologically and clinically meaningful insights into the molecular landscape of soft tissue sarcomas and supports its integration into precision medicine-oriented diagnostic workflows.