Osteosarcoma

NIR irradiation induces pyroptosis via caspase-3/GSDME activation and immunogenic cell death, while Ganetespib suppresses glycolysis (HK2/PKM2 downregulation) to reverse lactate-driven immunosuppression. This dual-action strategy synergistically enhances T-cell infiltration and ablates residual/metastatic lesions, offering a transformative approach for unresectable Osteosarcoma.

Multisystem disease remains more challenging, but favourable outcomes can still be achieved with protocol-based treatment. Early recognition, multidisciplinary evaluation, and long-term follow-up are essential due to the risk of relapse and potential late sequelae.

Collectively, our findings uncover that METTL3-mediated m6A modification of CACNA1E contributes to OS progression and chemoresistance through enhancing WNT7B-mediated non-canonical Wnt/Ca2+ signaling. Targeted inhibition of CACNA1E in combination with MTX may be a promising alternative therapeutic strategy for patients with MTX-resistant OS.

P2, N=1376, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> Jan 2027

Analysis of bulk RNA-seq data to estimate cell-type composition shows greater immune cell representation in metastases, underscoring the importance of immune signaling pathways in OS. These findings exemplify the presence of patient-specific alterations in genomic architecture over the course of tumor progression, linking CNV amplification, pathway reprogramming, and immune evasion in metastatic OS.

Aspirin suppressed the malignant progression of osteosarcoma by targeting the NF-κB/p65/PDE4D axis, positioning PDE4D as a potential therapeutic target for aspirin- based treatment strategies.

The H3-3A gene sequencing assay demonstrated a sensitivity of 87.16% and an absolute specificity of 100% among the cases analyzed in the study. Determination of the H3-3A gene mutation by sequencing is a highly sensitive and absolutely specific diagnostic tool for the diagnosis of GCTB and differentiation from its histologic mimics.

This external validation confirms the seven-gene signature as a potential biomarker for predicting ICI efficacy in advanced sarcomas. Prospective studies are needed to determine the prognostic versus predictive value of SIGNIOS, refine its use across sarcoma subtypes, and explore its applicability in other tumor types.

This study identifies UBR5 as a key driver of osteosarcoma progression and a promising diagnostic and prognostic biomarker across cancers, highlighting its potential as a biomarker and therapeutic target.

Our results also reveal changes in the conformational ensemble of the entire tail, re-positioning it on the nucleosomal DNA and promoting intra-tail interactions. We demonstrate that these changes in the nucleosome, produced by mutations, alter the association of a tandem of plant homeodomain-fingers from CHD4 with the unmodified H3 tails.

These engineered cells resist transforming growth factor β (TGF-β) suppression, secrete IL-15, and demonstrate improved cytotoxicity, persistence, and tumor homing in both in vitro and in vivo models. Our findings support CD70 CAR NK cells as a promising immunotherapeutic strategy for relapsed and metastatic OSA.

P1, N=30, Recruiting, Fred Hutchinson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: May 2026 --> Jan 2026