Liposarcoma

The eIF4A inhibitor CR-1-31B effectively suppressed tumor growth and induced apoptosis in DDLS, MFS, and UPS patient-derived cell lines and mouse xenografts...Genomic analysis of patient tumors revealed that YAP and WWTR1 were frequently amplified or gained in DDLS, MFS, and UPS and were associated with worse clinical outcomes. Together, our findings identify a new strategy for targeting the Hippo pathway in incurable forms of sarcoma based on inhibition of eIF4A-dependent translation of the key oncogenic transcription factors YAP and TAZ.

The algorithm also performed robustly in the TCGA-SARC data, although with a slightly different optimal cutoff, likely due to differences in gene panels, depth of sequencing, gene coverage, and bioinformatics pipelines. This study presents an effective strategy for screening DDLPS and potentially other MDM2-amplified sarcomas.

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

Immunohistochemistry plays a crucial role in interpreting a specific diagnosis or narrowing the differential diagnosis of SRCTs. Molecular genetic investigations are essential, particularly in cases exhibiting atypical or overlapping histologic and immunohistological features.

H3K27ac-marked enhancers were enriched near adipocytic marker genes in WDLPS and mesenchymal markers in DDLPS. Together, these findings reveal the cellular heterogeneity of tumor and immune compartments across liposarcoma subtypes and identify regulatory programs driving their differentiation states.

The patient remained recurrence-free at 12-month follow-up. This case emphasizes the critical role of multimodal medical imaging, rigorous histopathological evaluation, and molecular testing in establishing an accurate diagnosis and guiding appropriate management, while highlighting that Madelung's disease may occasionally present with atypical imaging features, such as nodules and septa which closely mimic a malignant lesion.

Our findings highlight peripheral immune profiles as candidate biomarkers for predicting and monitoring ICI efficacy in STS. Incorporating these immune markers could refine patient selection, reduce unnecessary toxicity, and support adaptive treatment strategies for patients with this rare and heterogenous cancer.

This study provides the longest prospective OS data for palbociclib in WD/DD LPS. CDK4/6 inhibition remains a relevant treatment option, especially for patients unsuitable for cytotoxic therapy. CDH18 expression was associated with clinical outcomes and represents an exploratory biomarker signal that warrants independent validation in future prospective, biomarker-focused studies.

It underscores the importance of thorough histopathologic evaluation and immunohistochemical profiling to establish an accurate diagnosis and avoid unnecessary aggressive treatment. Complete surgical excision remains essential for diagnosis and management.

P2, N=7, Active, not recruiting, USWM, LLC (dba US WorldMeds) | Trial completion date: Jul 2025 --> Jul 2026

Three parallel genome-wide CRISPR-Cas9 knockout screens were conducted in DDLPS cells to sensitize to palbociclib (CDK4 inhibitor), nutlin-3a (MDM2 inhibitor) or doxorubicin...Genetic perturbation of TDP2 or pharmacological inhibition of DNA-PKcs using peposertib synergized with prolonged administration of low-dose doxorubicin to induce cell cycle arrest and senescence, and subsequent senolytic treatment with Bcl2 inhibitor navitoclax triggered senescent cells to undergo apoptosis...These findings provide a rationale for targeting the NHEJ pathway to enhance the efficacy of low-dose doxorubicin in DDLPS, highlighting a potential therapeutic strategy exploiting p53-mediated cell cycle arrest and senescence. Furthermore, this study provides evidence of maintained baseline p53 activity in MDM2-amplified DDLPS.

P1, N=12, Active, not recruiting, Baylor College of Medicine | Recruiting --> Active, not recruiting | N=27 --> 12