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<p>Functional precision oncology (FPO) enables individualized therapy selection using patient-derived tumor models, yet the concordance of distinct ex vivo testing strategies remains unclear. Here, we compare two orthogonal drug sensitivity platforms across molecularly characterized models spanning diverse pediatric (<i>n</i> = 13) and adult (<i>n</i> = 6) cancers. A rapid ATP-based assay quantifies viability within three days, whereas a long-term dynamic image-based platform captures microtumor dynamics over two weeks, incorporating pharmacokinetic features. Up to 50 drugs were profiled across both platforms, with additional combinations evaluated in the long-term assay; genomics-guided targeted drugs served as benchmarks. Both approaches robustly distinguished responders from non-responders and showed strong agreement in therapeutic prioritization (96.5% within 95% limits of agreement). The long-term dynamic platform achieved 81% sensitivity and 78% specificity, while resolving response depth and distinguishing cytostatic from cytotoxic effects. A representative sarcoma case highlights clinical relevance: long-term dynamic profiling predicted disease progression, whereas the short-term assay captured early treatment-associated viability effects. These findings establish cross-platform reproducibility in FPO and provide a systematic benchmarking of such approaches. Defining their complementary utility will be essential for integrating FPO strategies into clinical decision-making.</p>

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Integration and validation of complementary ex vivo assays for functional precision oncology

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月17日

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  • Anna Loboda,
  • Jasmina Paluncic,
  • Micaela Freitas,
  • Marko Weidmann,
  • Sonja Herter,
  • Constantia Zeiser,
  • Juliana P. Schulz,
  • Attila Jády,
  • Mirjam Blattner-Johnson,
  • Robert J. Autry,
  • Karen Frese,
  • Dmitry Lupar,
  • Martin Schneider,
  • Roland Imle,
  • Ana Banito,
  • Hanno Glimm,
  • Olaf Witt,
  • Heike Peterziel,
  • Jens M. Kelm,
  • Claudia R. Ball,
  • Ina Oehme

摘要

Functional precision oncology (FPO) enables individualized therapy selection using patient-derived tumor models, yet the concordance of distinct ex vivo testing strategies remains unclear. Here, we compare two orthogonal drug sensitivity platforms across molecularly characterized models spanning diverse pediatric (n = 13) and adult (n = 6) cancers. A rapid ATP-based assay quantifies viability within three days, whereas a long-term dynamic image-based platform captures microtumor dynamics over two weeks, incorporating pharmacokinetic features. Up to 50 drugs were profiled across both platforms, with additional combinations evaluated in the long-term assay; genomics-guided targeted drugs served as benchmarks. Both approaches robustly distinguished responders from non-responders and showed strong agreement in therapeutic prioritization (96.5% within 95% limits of agreement). The long-term dynamic platform achieved 81% sensitivity and 78% specificity, while resolving response depth and distinguishing cytostatic from cytotoxic effects. A representative sarcoma case highlights clinical relevance: long-term dynamic profiling predicted disease progression, whereas the short-term assay captured early treatment-associated viability effects. These findings establish cross-platform reproducibility in FPO and provide a systematic benchmarking of such approaches. Defining their complementary utility will be essential for integrating FPO strategies into clinical decision-making.