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 Gojo; Caroline 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

doi:10.1038/s41698-022-00335-y

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

Department of Paediatrics and Adolescent Medicine

47 Citations (Scopus)

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.

Original language	English
Article number	94
Journal	NPJ precision oncology
Volume	6
Issue number	1
Pages (from-to)	1-17
Number of pages	17
ISSN	2397-768X
DOIs	https://doi.org/10.1038/s41698-022-00335-y
Publication status	Published - 27 Dec 2022

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Peterziel, H., Jamaladdin, N., ElHarouni, D., Gerloff, X. F., Herter, S., Fiesel, P., Berker, Y., Blattner-Johnson, M., Schramm, K., Jones, B. C., Reuss, D., Turunen, L., Friedenauer, A., Holland-Letz, T., Sill, M., Weiser, L., Previti, C., Balasubramanian, G., Gerber, N. U., ... Oehme, I. (2022). Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM. NPJ precision oncology, 6(1), 1-17. Article 94. https://doi.org/10.1038/s41698-022-00335-y

Peterziel, H, Jamaladdin, N, ElHarouni, D, Gerloff, XF, Herter, S, Fiesel, P, Berker, Y, Blattner-Johnson, M, Schramm, K, Jones, BC, Reuss, D, Turunen, L, Friedenauer, A, Holland-Letz, T, Sill, M, Weiser, L, Previti, C, Balasubramanian, G, Gerber, NU, Gojo, J, Hutter, C, Øra, I, Lohi, O, Kattamis, A, de Wilde, B, Westermann, F, Tippelt, S, Graf, N, Nathrath, M, Sparber-Sauer, M, Sehested, A, Kramm, CM, Dirksen, U, Kallioniemi, O, Pfister, SM, van Tilburg, CM, Jones, DTW, Saarela, J, Pietiäinen, V, Jäger, N, Schlesner, M, Kopp-Schneider, A, Oppermann, S, Milde, T, Witt, O & Oehme, I 2022, 'Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM', NPJ precision oncology, vol. 6, no. 1, 94, pp. 1-17. https://doi.org/10.1038/s41698-022-00335-y

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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.",

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AU - Peterziel, Heike

AU - Jamaladdin, Nora

AU - ElHarouni, Dina

AU - Gerloff, Xenia F

AU - Herter, Sonja

AU - Fiesel, Petra

AU - Berker, Yannick

AU - Blattner-Johnson, Mirjam

AU - Schramm, Kathrin

AU - Jones, Barbara C

AU - Reuss, David

AU - Turunen, Laura

AU - Friedenauer, Aileen

AU - Holland-Letz, Tim

AU - Sill, Martin

AU - Weiser, Lena

AU - Previti, Christopher

AU - Balasubramanian, Gnanaprakash

AU - Gerber, Nicolas U

AU - Gojo, Johannes

AU - Hutter, Caroline

AU - Øra, Ingrid

AU - Lohi, Olli

AU - Kattamis, Antonis

AU - de Wilde, Bram

AU - Westermann, Frank

AU - Tippelt, Stephan

AU - Graf, Norbert

AU - Nathrath, Michaela

AU - Sparber-Sauer, Monika

AU - Sehested, Astrid

AU - Kramm, Christof M

AU - Dirksen, Uta

AU - Kallioniemi, Olli

AU - Pfister, Stefan M

AU - van Tilburg, Cornelis M

AU - Jones, David T W

AU - Saarela, Jani

AU - Pietiäinen, Vilja

AU - Jäger, Natalie

AU - Schlesner, Matthias

AU - Kopp-Schneider, Annette

AU - Oppermann, Sina

AU - Milde, Till

AU - Witt, Olaf

AU - Oehme, Ina

PY - 2022/12/27

Y1 - 2022/12/27

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85145228241

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DO - 10.1038/s41698-022-00335-y

M3 - Journal article

C2 - 36575299

SN - 2397-768X

VL - 6

SP - 1

EP - 17

JO - NPJ precision oncology

JF - NPJ precision oncology

IS - 1

M1 - 94

ER -

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

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