| Autor: |
Al Shihabi, Ahmad, Davarifar, Ardalan, Nguyen, Huyen Thi Lam, Tavanaie, Nasrin, Nelson, Scott D, Yanagawa, Jane, Federman, Noah, Bernthal, Nicholas, Hornicek, Francis, Soragni, Alice |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Science advances, vol 8, iss 7 |
| Popis: |
Chordomas are rare tumors of notochordal origin, most commonly arising in the sacrum or skull base. Chordomas are considered insensitive to conventional chemotherapy, and their rarity complicates running timely and adequately powered trials to identify effective treatments. Therefore, there is a need for discovery of novel therapeutic approaches. Patient-derived organoids can accelerate drug discovery and development studies and predict patient responses to therapy. In this proof-of-concept study, we successfully established organoids from seven chordoma tumor samples obtained from five patients presenting with tumors in different sites and stages of disease. The organoids recapitulated features of the original parent tumors and inter- as well as intrapatient heterogeneity. High-throughput screenings performed on the organoids highlighted targeted agents such as PI3K/mTOR, EGFR, and JAK2/STAT3 inhibitors among the most effective molecules. Pathway analysis underscored how the NF-κB and IGF-1R pathways are sensitive to perturbations and potential targets to pursue for combination therapy of chordoma. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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