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

• Published in: NPJ precision oncology Vol. 6; no. 1; p. 94
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 27.12.2022; Nature Publishing Group UK; Nature Portfolio
• Subjects: Cancer; Cell culture; Computer science; Cooperation; Data analysis; DNA methylation; Hematology; Hospitals; Immunology; Medical research; Medicin och hälsovetenskap; Medicine; Neuropathology; Oncology; Patients; Pediatrics; Pulmonology; Research centers
• ISSN: 2397-768X; 2397-768X
• DOI: 10.1038/s41698-022-00335-y

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.