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

Heike Peterziel, Nora Jamaladdin, Dina ElHarouni, Xenia F Gerloff, Sonja Herter, Petra Fiesel, Yannick Berker, Mirjam Blattner-Johnson, Kathrin Schramm, Barbara C Jones, David Reuss, Laura Turunen, Aileen Friedenauer, Tim Holland-Letz, Martin Sill, Lena Weiser, Christopher Previti, Gnanaprakash Balasubramanian, Nicolas U Gerber, Johannes GojoCaroline Hutter, Ingrid Øra, Olli Lohi, Antonis Kattamis, Bram de Wilde, Frank Westermann, Stephan Tippelt, Norbert Graf, Michaela Nathrath, Monika Sparber-Sauer, Astrid Sehested, Christof M Kramm, Uta Dirksen, Olli Kallioniemi, Stefan M Pfister, Cornelis M van Tilburg, David T W Jones, Jani Saarela, Vilja Pietiäinen, Natalie Jäger, Matthias Schlesner, Annette Kopp-Schneider, Sina Oppermann, Till Milde, Olaf Witt, Ina Oehme

Abstract

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.

OriginalsprogEngelsk
Artikelnummer94
TidsskriftNPJ precision oncology
Vol/bind6
Udgave nummer1
Sider (fra-til)1-17
Antal sider17
ISSN2397-768X
DOI
StatusUdgivet - 27 dec. 2022

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