Chordoma

P2, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Nov 2025 --> Jul 2025

P2, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

BACH1-driven CM-TAMs activate TBLCs via the ANGPTL4-SDC4 signaling axis, promoting stemness and cholesterol accumulation, ultimately driving malignant progression in chordoma. These findings uncover a previously unrecognized tumor-immune-metabolic interaction and suggest potential therapeutic targets for this disease.

The current study suggests that eosinophils may be a new target for immunotherapy against chordoma.

Differential considerations, including epithelioid sarcoma, poorly differentiated chordoma, CRINET, choroid plexus carcinoma, and rare composite tumors, further complicate the diagnostic landscape. A comprehensive, multimodal diagnostic approach combining histologic, immunophenotypic, and molecular data is essential to accurately identify AT/RT and guide clinical management, particularly in diagnostically ambiguous or atypical cases.

This case underscores the importance of recognizing distinct features of malignant extrarenal rhabdoid tumor to ensure accurate diagnosis and early intervention, as the disease remains aggressive with a high risk of recurrence despite multimodal therapy.

P=N/A, N=54, Completed, Abramson Cancer Center at Penn Medicine | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Sep 2025 | Trial primary completion date: Dec 2026 --> Jul 2025

Importantly, co-treatments exhibited greater inhibition of tumor growth than single treatments in cell line- and patient-derived xenograft models. Taken together, our data revealed that THZ1 or TG02 enhanced in vitro and in vivo efficacy of afatinib, suggesting a potential novel combination therapeutic strategy for patients with chordoma.

The prototypic EPRS inhibitor halofuginone demonstrated significant tumour growth inhibition in an in vivo patient-derived xenograft model. These results suggest that targeting metabolic stress pathways via ATF4 activation presents a novel therapeutic approach for chordoma, warranting further clinical investigation.

P=N/A, N=188, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=300 --> 188

CD3L1 is expressed in osteosarcoma and chordoma and is associated with features of the tumor immune microenvironment, including markers of macrophage infiltration. As a potential therapeutic target, CD3L1 warrants further functional and clinical investigation.

This study provides a foundation for characterizing SBC through QSM, enabling indirect, non-invasive identification of potentially hypoxic tumor regions. Further histological validation with specific hypoxia markers, such as HIF-1α, is nevertheless required.