Sarcoma Diagnosis and Treatment

Role of Myc family proteins in transcriptional regulation of growth and oncogenic transformation in fusion-positive rhabdomyosarcoma

This study investigates the role of Myc family proteins in FP-RMS, showing MYCN or MYC dominance in some cases and functional redundancy in others, with both contributing to oncogenic properties.

ATRX Loss Predicts Poor Outcomes and Reveals a Therapeutic Vulnerability to TEAD Inhibition in Soft Tissue Sarcomas

This study shows ATRX loss in sarcomas correlates with poor outcomes and identifies TEAD inhibition as a potential therapy for ATRX-deficient tumors.

Proteogenomic profiling of soft tissue leiomyosarcoma reveals distinct molecular subtypes with divergent outcomes and therapeutic vulnerabilities

This study identifies three proteogenomic subtypes of soft tissue leiomyosarcoma with distinct molecular features and clinical outcomes, suggesting potential therapeutic targets.

Efficacy of Minnelide in a Next-Generation Dual-Recombinase Regulated Genetically Engineered Mouse Model of CIC::DUX4 Sarcoma

This paper develops a new mouse model of CIC::DUX4 sarcoma and identifies Minnelide as a selective inhibitor effective in preclinical models.

Prognosis prediction using autophagy gene expression in osteosarcoma

This paper develops Auto-RS, a computational classifier using autophagy gene expression to predict osteosarcoma prognosis and identify therapeutic vulnerabilities.

Delayed growth of Ewing sarcoma tumors associated with reduced expression and activity of Trk receptors, PI3K, and IGF1R

The paper shows that K252a treatment delays Ewing sarcoma tumor growth and reduces Trk, PI3K, and IGF1R expression and activity, with combined treatment more effective than single agents.

EGR1 Mediates Riluzole-Induced Apoptosis in Osteosarcoma via the Yap/p73-Bax Signaling Axis

This study shows Riluzole induces apoptosis in osteosarcoma by upregulating EGR1, which interacts with Yap/p73 to enhance Bax expression and promote cell death.

Origin of Ewing sarcoma by embryonic reprogramming of neural crest to mesoderm

This study identifies neural crest cells as the origin of Ewing sarcoma by developing a zebrafish model and showing EWSR1::FLI1 reprograms these cells to a mesoderm-like state.

NR0B1 alters the 9-cis-retinoic acid response in Ewing Sarcoma cells

This study shows NR0B1 alters the 9-cis-retinoic acid response in Ewing Sarcoma cells by modulating nuclear receptor activity, suggesting NR0B1 inhibition could enhance retinoid therapy.

CK2 inhibitor CX-4945 targets EWS-FLI1 signaling network and shows therapeutic efficacy in metastatic mouse models of Ewing Sarcoma

This study shows that CK2 inhibitor CX-4945 targets EWS-FLI1 and reduces tumor growth and metastasis in Ewing Sarcoma models.

Molecular Basis of EWS Interdomain Self-Association and Its Role in Condensate Formation

This paper investigates how EWS's RNA-binding domains interact with its low-complexity domain to influence condensate formation, revealing electrostatic and residue-specific interactions that underlie EWS self-association.

Leveraging Experimental Evolution to Extract Predictive Collateral Drug Response Signatures in Ewings Sarcoma

The paper experimentally evolves resistance in Ewings sarcoma cell lines to identify gene expression signatures predicting collateral drug responses, validated in an independent cell line.

Blockade of Interleukin-6 (IL-6) Signaling in Dedifferentiated Liposarcoma (DDLPS) Decreases Mouse Double Minute 2 (MDM2) Oncogenicity via Alternative Splicing

This study shows that blocking IL-6 signaling in DDLPS reduces MDM2 oncogenicity through alternative splicing, suggesting a potential therapeutic target.

Immunocompetent murine models recapitulate the heterogeneous tumor immune microenvironment of human liposarcoma

This study develops an immunocompetent mouse model of liposarcoma that recapitulates human tumor subtypes and immune features, enabling preclinical immunotherapy research.

PAX3-FOXO1 drives targetable cell state-dependent metabolic vulnerabilities in rhabdomyosarcoma

This study shows that PAX3-FOXO1 drives metabolic vulnerabilities in rhabdomyosarcoma, making these cells sensitive to methotrexate.

Riluzole as a Dual-Targeted Radiosensitizer for Osteosarcoma: Targeting Tumor Cells and Angiogenic Vasculature to Enhance Single High Dose Radiotherapy Efficacy

This paper demonstrates that Riluzole enhances osteosarcoma radiosensitivity to single high dose radiotherapy by targeting both tumor cells and angiogenic vasculature.

Targeting CXADR-mediated AKT signaling suppresses tumorigenesis and enhances chemotherapy efficacy in Ewing sarcoma

This study identifies CXADR as a driver of Ewing sarcoma metastasis and shows that targeting AKT signaling with Capivasertib enhances chemotherapy efficacy in CXADR-high tumors.

Dual Targeting of MAPK Signaling and Senescence-Associated Survival Pathways Overcomes Vincristine Resistance in Fusion-Negative Rhabdomyosarcoma

This paper identifies MAPK signaling and MYC-driven suppression of p21 as mechanisms of vincristine resistance in fusion-negative rhabdomyosarcoma and shows that dual targeting of MAPK and BCL-XL pathways overcomes resistance.

RUNX2 inhibition disrupts a PAX3::FOXO1-RUNX2 feed-forward loop and dismantles oncogenic gene programs in fusion-positive rhabdomyosarcoma

This study identifies RUNX2 as a druggable target in fusion-positive rhabdomyosarcoma, showing its inhibition disrupts a PAX3::FOXO1-RUNX2 feed-forward loop and reduces tumor growth.

Divergent Therapeutic and Prognostic Impacts of Immunogenic Features in Undifferentiated Soft Tissue Sarcoma and Myxofibrosarcoma

This study compares immunogenic features between undifferentiated soft tissue sarcoma and myxofibrosarcoma, finding differences in T cell and macrophage infiltration and their prognostic significance.

Rhabdomyosarcoma fusion oncoprotein initially pioneers a neural signature in vivo

The paper identifies PAX3::FOXO1's pioneer function through partial/homeobox motif recognition and its role in initiating neural transcriptional programs in rhabdomyosarcoma.

Single-Cell and Spatial Profiling of Tumor Microenvironment Heterogeneity in Human Osteosarcomas

This study uses single-cell and spatial transcriptomics to analyze tumor microenvironment heterogeneity in osteosarcomas, identifying distinct cellular states and spatial niches.

N'-(1-phenylethylidene)-benzohydrazide cytotoxicity is LSD1 independent and linked to Fe-S cluster disruption in Ewing sarcoma

This paper identifies that SP-2509 and SP-2577, LSD1 inhibitors, induce cell death in Ewing sarcoma through Fe-S cluster disruption, independent of LSD1 inhibition.

Multimodal single-cell analyses reveal distinct fusion-regulated transcriptional programs in Ewing sarcoma.

The paper identifies distinct transcriptional programs in Ewing sarcoma driven by EWS::FLI1 fusions and shows their variability across tumors and cell lines.

Ephrin-A5 and EphA7 stimulation is anti-proliferative for human rhabdomyosarcoma in vitro

This study shows that EphA7 and ephrin-A5 regulate rhabdomyosarcoma proliferation, with ephrin-A5 being a potential therapeutic target for differentiation therapy.

Molecular Feature-Based Classification of Retroperitoneal Liposarcoma: A Prospective Cohort Study

This study classifies retroperitoneal liposarcoma into two subtypes using molecular features, showing improved survival outcomes for one subtype based on biomarkers LEP and PTTG1.

Repurposing Romidepsin for Osteosarcoma: Screening FDA-Approved Oncology Drugs with Three-Dimensional Osteosarcoma Spheroids

This paper identifies romidepsin as a promising repurposed drug for osteosarcoma using 3D spheroid models, showing efficacy against metastatic cells and outperforming other HDIs.

Dynamic oncogene activity metabolically reprograms the tryptophan-kynurenine-AHR axis driving immune evasion and tumor progression in Ewing sarcoma

This study shows that reduced EWSR1::ETS activity in Ewing sarcoma promotes immune evasion via the tryptophan-kynurenine-AHR axis, leading to worse clinical outcomes and tumor progression.

Fusion transcription factor dosage controls cell state in rhabdomyosarcoma

This study shows that varying levels of PAX3::FOXO1 protein affect cell state and epigenetic heterogeneity in rhabdomyosarcoma.

SLFN11 Loss-Induced Chemoresistance is Associated with Overexpression of Glycerophospholipid Biosynthesis in Ewing Sarcoma.

The paper identifies glycerophospholipid biosynthesis upregulation as a mechanism of chemoresistance in SLFN11-loss Ewing sarcoma and shows that inhibiting this pathway enhances DNA-damaging agent efficacy.