Sarcoma Diagnosis and Treatment

EWS::WT1 Isoform-Dependent Regulation of Neogenes in Desmoplastic Small Round Cell Tumors

This study identifies DSRCT-specific neogenes regulated by the EWS::WT1 fusion protein and shows their potential as biomarkers and therapeutic targets in desmoplastic small round cell tumors.

Collagen targeting IL-12 combined with Doxorubicin enhances the anti-tumor effect against osteosarcoma

This study combines collagen-targeted IL-12 with doxorubicin to improve anti-tumor effects in osteosarcoma by enhancing tumor accumulation and immune activation.

Menin inhibition impairs metastatic colonization of Ewing sarcoma

This study shows Menin inhibition reduces metastatic colonization of Ewing sarcoma in vivo by disrupting MYC target gene expression and Menin:MYC interactions.

SRF fusion oncogenes encode constitutively activated chimeric transcription factors in myoid soft tissue tumors

MIR17HG Expression Is Transcriptionally Regulated by PAX3::FOXO1 and MYCN 1 and is Necessary for Oncogenic Activity in Fusion-Positive Rhabdomyosarcoma

This study identifies PAX3::FOXO1 and MYCN as cooperative regulators of MIR17HG expression in fusion-positive rhabdomyosarcoma and shows miR-17-92 is necessary for oncogenic activity.

PPARG governs adipogenic differentiation and cell state plasticity in well-differentiated and dedifferentiated liposarcoma

This study identifies PPARG as a key regulator of adipogenic differentiation in liposarcoma, showing its loss contributes to the aggressive phenotype of dedifferentiated liposarcoma.

Proteome-wide multi-omics profiling of osteosarcoma transcription factor networks

This study uses proteomics and gene expression data to identify transcription factor networks associated with osteosarcoma aggressiveness in different cell lines.

CDK8 Inhibition Releases the Muscle Differentiation Block in Fusion-driven Alveolar Rhabdomyosarcoma

This study identifies CDK8 inhibition as a therapeutic strategy for alveolar rhabdomyosarcoma by inducing myogenic differentiation and impairing tumor growth through a mechanism involving the Mediator kinase module, SAGA complex, and SIX4.

A novel combination of CDK4/6 and PI3K inhibitors exhibits highly synergistic activity and translational potential in Ewing sarcoma.

This paper identifies a synergistic combination of CDK4/6 and PI3K inhibitors that shows strong anti-Ewing sarcoma activity and improved survival in a xenograft model.

Mevalonate pathway activation in Ewing sarcoma reveals a 3D-specific synergy between statins and BCL-xL inhibition

The paper develops a 3D culture platform for Ewing sarcoma and identifies a synergy between statins and BCL-xL inhibitors targeting the mevalonate pathway.

TAK1 is a key regulator of oncogenic signaling and differentiation blockade in rhabdomyosarcoma

This study identifies TAK1 as a key regulator of oncogenic signaling and differentiation blockade in rhabdomyosarcoma, showing its role in promoting proliferation and inhibiting myogenic differentiation.

Spatial single cell transcriptomic analysis of a novel DICER1 Syndrome GEMM informs the cellular origin and developmental hierarchy of associated sarcomas

This study uses a mouse model to identify a fibroblastic origin for DICER1 sarcomas and shows their potential to differentiate into rhabdomyoblastic or anaplastic sarcomas.

Comprehensive single cell transcriptomics analysis of murine osteosarcoma uncovers Skp2 function in metastasis, genomic instability and immune activation and reveals additional target pathways

This study uses scRNA-seq to analyze murine osteosarcoma models and identifies Skp2's role in metastasis, genomic instability, and immune activation, revealing potential therapeutic targets.

cIAP1 inhibitor of apoptosis is a tumor suppressor in Ewing sarcoma

This study identifies cIAP1 as a tumor suppressor in Ewing sarcoma, showing that its re-expression inhibits proliferation and tumor growth in vitro and in vivo.

LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing Sarcoma

This study defines the enzymatic and nonenzymatic roles of LSD1 in Ewing sarcoma using genetic and pharmacological approaches, revealing gene repression and its impact on synapse function and e-cadherin targets.

VCAN is essential for ERK5-driven tumorigenesis in soft tissue sarcoma

This study identifies VCAN as a novel transcriptional target of ERK5 and shows its essential role in ERK5-driven tumorigenesis in soft tissue sarcoma.

Autocrine TGFβ2 enforces a transcriptionally hybrid cell state in Ewing sarcoma

The paper identifies TGFβ2 as a driver of a hybrid transcriptional state in Ewing sarcoma cells, promoting metastasis through ECM deposition and invasion.

Epigenetic dysregulation of metabolic programs mediates liposarcoma cell plasticity

This study identifies epigenetic dysregulation of metabolic programs in liposarcoma, linking IGF1 loss and PPARG2 deficiency to dedifferentiation and proposing IGF1R-targeted therapy.

Human fibrosarcoma cells selected for very-high doxorubicin resistance, acquire trabectedin and eribulin cross-resistance, remain sensitive to recombinant methioninase, and have increased c-MYC expression

This study shows that doxorubicin-resistant fibrosarcoma cells are cross-resistant to trabectedin and eribulin but remain sensitive to recombinant methioninase, with increased c-MYC expression.

Cell-of-origin epigenome underlies SS18::SSX-mediated transformation

This study identifies the cell-of-origin of synovial sarcoma as a rare fibroblastic population and shows that SS18::SSX induces an embryonic-like mesenchymal stem cell phenotype.

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.

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.

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.

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.

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.