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| Status |
Public on Aug 31, 2024 |
| Title |
ATF4-Mediated Metabolic Stress Response as a Therapeutic Vulnerability in Chordoma [MUG-Chor RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Chordoma, a rare and challenging primary bone malignancy, currently lacks effective targeted therapies. Despite surgical resection and adjuvant radiotherapy, prognosis remains poor. Recent preclinical studies have highlighted potential therapeutic targets, including the transcription factor TBXT, although clinical outcomes have been modest. In this study, we investigated the therapeutic potential of tRNA synthetase inhibitors, specifically halofuginone and halofuginol, in chordoma treatment. We conducted extensive drug screening, identifying these compounds as effective in reducing cell viability in chordoma cell lines through an ATF4-mediated stress response rather than TBXT regulation. Our findings were validated using RNA sequencing, which revealed significant upregulation of ATF4 and associated stress response genes. Additionally, 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.
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| Overall design |
Examination of gene expression differences in MUG-Chor cell line in response to DMSO control, Halofuginone and Halufuginol over 0, 6, 24 and 72 hours
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| Contributor(s) |
Cribbs AP |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Aug 22, 2024 |
| Last update date |
Aug 31, 2024 |
| Contact name |
Adam Cribbs |
| E-mail(s) |
adam.cribbs@ndorms.ox.ac.uk
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| Organization name |
University of Oxford
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| Department |
NDORMS
|
| Street address |
Windmill Road
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| City |
Oxford |
| ZIP/Postal code |
OX37LD |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (40)
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| This SubSeries is part of SuperSeries: |
| GSE275637 |
ATF4-Mediated Metabolic Stress Response as a Therapeutic Vulnerability in Chordoma |
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| Relations |
| BioProject |
PRJNA1150969 |
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