Liposarcoma

Thus, our findings suggest that in-frame TERT fusions may drive the pathogenesis of a group of mostly low-grade unclassified sarcomas with fibroblastic/myofibroblastic differentiation. In contrast, TERT fusions may also be detected in other common sarcoma types co-occurring with numerous genomic alterations, likely representing a secondary driver event.

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

P1/2, N=7, Active, not recruiting, Sotio Biotech Inc. | Trial primary completion date: Oct 2027 --> Oct 2025

P1, N=8, Not yet recruiting, Northwestern University

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.

A palbociclib lead-in prior to retifanlimab had a high rate of immune-related toxicities. Correlative analyses identified changes in tumor and immune cells attributable to treatment. A study of concurrent dosing of the combination is ongoing.

Emerging therapies targeting the MDM2 and CDK4 pathways show promise for advanced or recurrent cases. This report highlights the complexity of diagnosing and managing paratesticular liposarcomas, underlining the importance of multimodal approaches for improved outcomes.

This is the first reported case of recurrent retroperitoneal DDLPS with high TMB achieving pCR to pembrolizumab. High TMB and high TAM density in the tumor microenvironment may be predictive biomarkers for the response to ICIs in DDLPS.

Integration of these molecular markers into diagnostic and prognostic workflows may enhance subtype characterization and inform targeted therapeutic strategies. Further studies in larger cohorts are warranted to validate these biomarkers and explore their mechanistic interplay in liposarcoma pathogenesis.

Also, investigation of somatic mutations of oncogenes and tumor suppressors revealed that in liposarcoma and rhabdomyosarcoma, there are mutations that induce proliferative signals. These proliferative signals, joined with bFGF in the presence of DHA, do not lead to proliferation but instead cause cell death.

Despite low overall expression rates, PD-L1 could serve as a prognostic biomarker and a potential target for immunotherapeutic strategies in liposarcomas. Further studies are necessary to standardize PD-L1 assessment and explore effective immunotherapy approaches for these tumors.