Marlinde C. Schoonbeek, Pierre Gestraud, Lindy Vernooij, Arjan Boltjes, Vicky Amo-Addae, Marloes van Luik, Elaine Del Nery, Angela Bellini, Ellora Hui Zhen Chua, Sarah E. M. Swaak, Eleonora J. Looze, Vilja Pietiäinen, Laura Turunen, Jani Saarela, Julia Schüler, Émilie Indersie, Dennis Gürgen, Katia Scotlandi, Angelika Eggert, Rachida Bouarich, F. Bourdeaut, Sakina Zaïdi, Didier Surdez, Ángel M. Carcaboso, Birgit Geoerger, Aniello Federico, Marcel Kool, Yasmine Iddir, Alexandra Saint-Charles, Elnaz Saberi-Ansari, Florence Cavalli, Apurva Gopisetty, Eva Maria Rief, Hubert Caron, Lou Stancato, Gilles Vassal, Stefan Pfister, Jan Koster, Selma Eising, Sander R. van Hooff, Marlinde L. van den Boogaard, Gudrun Schleiermacher, Jan J. Molenaar
Pediatric patients with high-risk extra-cranial solid tumors face a 5-year survival rate below 50%. As molecular profiling alone is insufficient to guide treatment at relapse, complementary strategies like drug screening are urgently needed. We evaluated short-term drug screening as a rapid, reliable method to assess drug sensitivities in pediatric solid tumors using ex vivo cultures from previously established patient-derived xenograft (PDX) models. Ex vivo drug screening was performed within 14 days of receipt across two institutes, testing 77-224 compounds depending on cell availability. Drug responses were consistent across institutes (n = 6), and effective compounds were reproducibly identified in a replicate model. Tumor type-specific responses were observed. In neuroblastoma, ALK-mutation status did not correlate with ALK-inhibitor response, whereas correlations with transcriptomic changes were observed. Timepoint-specific drug sensitivities were observed in serial Ewing sarcoma models. Overall, drug hits were identified in 94% of screens (n = 63), broadening treatment options for 88% of cases without targetable alterations (n = 11). In case of a targetable event, drug screening refined compound choice. Ex vivo drug screening is a fast and feasible method, providing insights into compound efficacy and enabling quick identification of functional treatment suggestions. Ex vivo drug screening should be integrated into a future next-generation diagnostic platform for pediatric solid tumors, combined with genomics and transcriptomics.