Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 v...

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Detalles Bibliográficos
Autores principales: Peterziel, Heike, Jamaladdin, Nora, ElHarouni, Dina, Gerloff, Xenia F., Herter, Sonja, Fiesel, Petra, Berker, Yannick, Blattner-Johnson, Mirjam, Schramm, Kathrin, Jones, Barbara C., Reuss, David, Turunen, Laura, Friedenauer, Aileen, Holland-Letz, Tim, Sill, Martin, Weiser, Lena, Previti, Christopher, Balasubramanian, Gnanaprakash, Gerber, Nicolas U., Gojo, Johannes, Hutter, Caroline, Øra, Ingrid, Lohi, Olli, Kattamis, Antonis, de Wilde, Bram, Westermann, Frank, Tippelt, Stephan, Graf, Norbert, Nathrath, Michaela, Sparber-Sauer, Monika, Sehested, Astrid, Kramm, Christof M., Dirksen, Uta, Kallioniemi, Olli, Pfister, Stefan M., van Tilburg, Cornelis M., Jones, David T. W., Saarela, Jani, Pietiäinen, Vilja, Jäger, Natalie, Schlesner, Matthias, Kopp-Schneider, Annette, Oppermann, Sina, Milde, Till, Witt, Olaf, Oehme, Ina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794727/
https://www.ncbi.nlm.nih.gov/pubmed/36575299
http://dx.doi.org/10.1038/s41698-022-00335-y
Descripción
Sumario:The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.

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