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<p>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 (<i>n</i> = 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 (<i>n</i> = 63), broadening treatment options for 88% of cases without targetable alterations (<i>n</i> = 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.</p>

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Ex vivo drug sensitivity profiling to complement molecular profiling in pediatric precision oncology

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月10日

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  • Marlinde C. Schoonbeek,
  • Pierre Gestraud,
  • Lindy Vernooij,
  • Arjan Boltjes,
  • Vicky Amo-Addae,
  • Marloes van Luik,
  • Elaine Del Nery,
  • Angela Bellini,
  • Ellora Chua,
  • Sarah Swaak,
  • Eleonora J. Looze,
  • Vilja M. Pietiäinen,
  • Laura L. Turunen,
  • Jani S. Saarela,
  • Julia Schueler,
  • Emilie Indersie,
  • Dennis Gürgen,
  • Katia Scotlandi,
  • Angelika Eggert,
  • Rachida Bouarich-Bourimi,
  • Franck Bourdeaut,
  • Sakina Zaidi,
  • 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 N. 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

摘要

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.