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

Peterziel, Heike ; Jamaladdin, Nora ; ElHarouni, Dina ; Gerloff, Xenia F. ; Herter, Sonja ; Fiesel, Petra ; Berker, Yannick ; Blattner-Johnson, Mirjam ; Schramm, Kathrin and Jones, Barbara C. , et al. (2022) In NPJ precision oncology 6. p.1-17
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
in
NPJ precision oncology
volume
6
article number
94
pages
1 - 17
publisher
Springer Nature
external identifiers
  • scopus:85145228241
  • pmid:36575299
ISSN
2397-768X
DOI
10.1038/s41698-022-00335-y
language
English
LU publication?
no
additional info
Publisher Copyright: © 2022, The Author(s).
id
8b85396f-d798-4ce5-8b56-02fd72f8f77e
date added to LUP
2023-01-10 18:23:05
date last changed
2024-06-13 15:07:55
@article{8b85396f-d798-4ce5-8b56-02fd72f8f77e,
  abstract     = {{<p>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.</p>}},
  author       = {{Peterziel, Heike and Jamaladdin, Nora and ElHarouni, Dina and Gerloff, Xenia F. and Herter, Sonja and Fiesel, Petra and Berker, Yannick and Blattner-Johnson, Mirjam and Schramm, Kathrin and Jones, Barbara C. and Reuss, David and Turunen, Laura and Friedenauer, Aileen and Holland-Letz, Tim and Sill, Martin and Weiser, Lena and Previti, Christopher and Balasubramanian, Gnanaprakash and Gerber, Nicolas U. and Gojo, Johannes and Hutter, Caroline and Øra, Ingrid and Lohi, Olli and Kattamis, Antonis and de Wilde, Bram and Westermann, Frank and Tippelt, Stephan and Graf, Norbert and Nathrath, Michaela and Sparber-Sauer, Monika and Sehested, Astrid and Kramm, Christof M. and Dirksen, Uta and Kallioniemi, Olli and Pfister, Stefan M. and van Tilburg, Cornelis M. and Jones, David T.W. and Saarela, Jani and Pietiäinen, Vilja and Jäger, Natalie and Schlesner, Matthias and Kopp-Schneider, Annette and Oppermann, Sina and Milde, Till and Witt, Olaf and Oehme, Ina}},
  issn         = {{2397-768X}},
  language     = {{eng}},
  pages        = {{1--17}},
  publisher    = {{Springer Nature}},
  series       = {{NPJ precision oncology}},
  title        = {{Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM}},
  url          = {{http://dx.doi.org/10.1038/s41698-022-00335-y}},
  doi          = {{10.1038/s41698-022-00335-y}},
  volume       = {{6}},
  year         = {{2022}},
}