Chordoma

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.

Biomarker-guided repurposing of therapies approved in other tumors remains the fastest path to redefining the treatment model, but chordoma rarity and low mutation burden limit the impact of genomics in target discovery. This analysis indicates several potential candidate drugs that may be rapidly deployable in a clinical trial setting.

Mechanistically, REGγ regulates chordoma progression through the ubiquitin- and ATP-independent degradation of RIT1, which modulates the RIT1-MAPK pathway. Inhibition of RIT1 in REGγ-knockdown cells and patient-derived organoids alleviated these effects, suggesting that targeting REGγ may be a promising strategy for chordoma treatment.

P=N/A, N=64, Active, not recruiting, Massachusetts General Hospital | Phase classification: P2 --> P=N/A | Trial completion date: Mar 2032 --> Dec 2027 | Trial primary completion date: Mar 2022 --> Jun 2027