Dokument: A clinically compatible in vitro drug-screening platform identifies therapeutic vulnerabilities in primary cultures of brain metastases
| Titel: | A clinically compatible in vitro drug-screening platform identifies therapeutic vulnerabilities in primary cultures of brain metastases | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=67839 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20241203-102249-1 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Dateien: |
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| Stichwörter: | Spheroid cultures, High-throughput drug screening, Brain metastasis, Personalized medicine | |||||||
| Beschreibung: | Purpose
Brain metastases represent the most common intracranial tumors in adults and are associated with a poor prognosis. We used a personalized in vitro drug screening approach to characterize individual therapeutic vulnerabilities in brain metastases. Methods Short-term cultures of cancer cells isolated from brain metastasis patients were molecularly characterized using next-generation sequencing and functionally evaluated using high-throughput in vitro drug screening to characterize pharmacological treatment sensitivities. Results Next-generation sequencing identified matched genetic alterations in brain metastasis tissue samples and corresponding short-term cultures, suggesting that short-term cultures of brain metastases are suitable models for recapitulating the genetic profile of brain metastases that may determine their sensitivity to anti-cancer drugs. Employing a high-throughput in vitro drug screening platform, we successfully screened the cultures of five brain metastases for response to 267 anticancer compounds and related drug response to genetic data. Among others, we found that targeted treatment with JAK3, HER2, or FGFR3 inhibitors showed anti-cancer effects in individual brain metastasis cultures. Conclusion Our preclinical study provides a proof-of-concept for combining molecular profiling with in vitro drug screening for predictive evaluation of therapeutic vulnerabilities in brain metastasis patients. This approach could advance the use of patient-derived cancer cells in clinical practice and might eventually facilitate decision-making for personalized drug treatment. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Jeising, S., Nickel, A.-C., Trübel, J., Felsberg, J., Picard, D., Leprivier, G., Wolter, M., Huynh, M. K., Baca Olivera, M., Kaulich, K., Häberle, L., Esposito, I., Klau, G., Steinmann, J., Beez, T., Rapp, M., Sabel, M., Dietrich, S., Remke, M., … Qin, N. (2024). A clinically compatible in vitro drug-screening platform identifies therapeutic vulnerabilities in primary cultures of brain metastases. Journal of Neuro-Oncology, 169(3), 613–623. https://doi.org/10.1007/s11060-024-04763-7 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 03.12.2024 | |||||||
| Dateien geändert am: | 03.12.2024 |
