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Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma

3 Sept 2025

Abstract excerpt

The embryonic transcription factor TBXT (brachyury) drives chordoma, a spinal neoplasm without effective drug therapies. TBXT's regulatory network is poorly understood, and strategies to disrupt its activity for therapeutic purposes are lacking. We developed designed ankyrin repeat proteins that block TBXT-DNA binding (T-DARPins). In chordoma cells, T-DARPins reduced cell cycle progression, spheroid formation,...

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PMID: 40901948
DOI: 10.1126/sciadv.adu2796

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Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordomaPMID 40901948Read ↗

Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordomaSemantic proximity Read ↗

Mapping the landscape of genetic dependencies in chordomaSemantic proximity Read ↗

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An integrated functional genomics approach identifies the regulatory network directed by brachyury (<i>T</i>) in chordomaSemantic proximity Read ↗

Transcriptional Profiling Supports the Notochordal Origin of Chordoma and Its Dependence on a TGFB1-TBXT NetworkSemantic proximity Read ↗

Emerging target discovery and drug repurposing opportunities in chordomaSemantic proximity Read ↗

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