Chordoma

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

These two enzymes are potential targets for chordoma treatment, as well as for combination drugs treatment. It should be emphasized that the above analysis lacks experimental verification.

We conducted a Phase II Trial (Abscopal 5001 trial; NCT04713371) in patients with metastatic solid cancer to assess the safety and efficacy of cryoablation with concurrent injection of RPT-01-5001 (combination of low-dose checkpoint inhibitors and cyclophosphamide), a treatment process referred to as Multiplex Intratumoral Immunotherapy (MITITM)...The injection site cancer response was observed in nine (69%) patients, and the distal abscopal effect was seen in four (31%), including one sarcoma patient with a complete abscopal response of lung metastases and one bladder cancer patient with biopsy-confirmed complete resolution of lung and liver metastases. MITI with RPT-01-5001 is safe and highly feasible, providing 77% disease control and 31% of the abscopal effect in patients with metastatic cancer who have failed standard therapies.

P2, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting

P1/2, N=27, Recruiting, University of Florida | Initiation date: Aug 2025 --> Nov 2025