Osteosarcoma

This study reveals that Nob enhances Dox-induced ERS and apoptosis by inhibiting the PI3K-AKT pathway, thereby increasing the sensitivity of OS cells to Dox. This discovery offers a promising new strategy for the treatment of OS.

We demonstrate marked tumor growth inhibition in all FP-RMS PDXs treated with single agent FGF401 (FGFR4-specific inhibitor) and single agent lenvatinib (multi-kinase FGFR-inhibitor), and report a clinical response to lenvatinib in a relapsed metastatic FP-RMS patient. Altogether, we identified new sarcoma patients who may benefit from FGFR-inhibitors, most notably FP-rhabdomyosarcoma via FGFR4/FGF8 co-expression.

Subsequent bioinformatics analysis identified 8 core targets involved in TQ's anti-OS activity. Enrichment analysis indicated that these core targets modulate a range of biological processes and may influence multiple molecular pathways.ResultsPreliminary in vitro data indicated that TQ effectively reduces OS cell proliferation, induces apoptosis, and downregulates the expression of P53 and HMOX1 proteins.ConclusionOur findings elucidate the molecular mechanisms underlying TQ's effectiveness against OS, highlighting potential apoptosis-related therapeutic targets, such as P53 and CYCLIN D1, for the treatment of OS with TQ.

P1, N=48, Not yet recruiting, A-Seeds Australia Pty Ltd

In zebrafish, expression of closed ezrin rescued the metastatic capability of ezrin-null osteosarcoma xenografts. Our findings demonstrate that the closed conformation of ezrin-previously thought to be inactive-can directly bind RNA, regulate transcription and translation, and contribute to a metastatic phenotype in osteosarcoma cells.

P1/2, N=31, Completed, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Active, not recruiting --> Completed | N=84 --> 31

P1/2, N=56, Recruiting, Peking University People's Hospital

P1, N=30, Active, not recruiting, Cellectar Biosciences, Inc. | Trial primary completion date: Dec 2025 --> Aug 2026

P2, N=45, Recruiting, Memorial Sloan Kettering Cancer Center

Human ligand-based OSM CAR-T cells displayed anti-tumor effects against multiple osteosarcoma cell lines and patient samples. These effects were demonstrated in vitro, in xenograft models, and against a model simulating metastatic disease. Overall, this data supports the continued study of OSM-CAR-T cells as a new therapeutic avenue for osteosarcoma.

P=N/A, N=60, Recruiting, Universitaire Ziekenhuizen KU Leuven | Trial completion date: Jul 2025 --> Dec 2026 | Trial primary completion date: Jul 2025 --> Dec 2026

Notably, while ferroptosis represents a key mechanism, STAT3 may also contribute to anlotinib resistance through additional pathways including apoptosis, autophagy, and immune evasion, reflecting the multifunctional role of this central signaling hub. Our results delineate a novel mechanism wherein METTL3 governs ferroptosis and anlotinib resistance in osteosarcoma through dual m6A methylation of circFAM120B and pri-miR-330, offering potential targets for overcoming therapeutic resistance.