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 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 (Corresponding Author)

Research output: Contribution to journal › Article › peer-review

44 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
DOIs	https://doi.org/10.1038/s41698-022-00335-y
Publication status	Published - Dec 2022
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Field of Science*

3.2 Clinical medicine
3.1 Basic medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

Access to Document

10.1038/s41698-022-00335-yLicence: CC BY

Cite this

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), Article 94. https://doi.org/10.1038/s41698-022-00335-y

@article{b01f6cbda14f4faab686eff177156124,

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

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.",

author = "Heike Peterziel and Nora Jamaladdin and Dina ElHarouni and Gerloff, \{Xenia F.\} and Sonja Herter and Petra Fiesel and Yannick Berker and Mirjam Blattner-Johnson and Kathrin Schramm and Jones, \{Barbara C.\} and David Reuss and Laura Turunen and Aileen Friedenauer and Tim Holland-Letz and Martin Sill and Lena Weiser and Christopher Previti and Gnanaprakash Balasubramanian and Gerber, \{Nicolas U.\} and Johannes Gojo and Caroline Hutter and Ingrid {\O}ra and Olli Lohi and Antonis Kattamis and \{de Wilde\}, Bram and Frank Westermann and Stephan Tippelt and Norbert Graf and Michaela Nathrath and Monika Sparber-Sauer and Astrid Sehested and Kramm, \{Christof M.\} and Uta Dirksen and Olli Kallioniemi and Pfister, \{Stefan M.\} and \{van Tilburg\}, \{Cornelis M.\} and Jones, \{David T.W.\} and Jani Saarela and Vilja Pieti{\"a}inen and Natalie J{\"a}ger and Matthias Schlesner and Annette Kopp-Schneider and Sina Oppermann and Till Milde and Olaf Witt and Ina Oehme",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41698-022-00335-y",

language = "English",

volume = "6",

journal = "npj Precision Oncology",

issn = "2397-768X",

publisher = "Nature Research",

number = "1",

}

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. https://doi.org/10.1038/s41698-022-00335-y

TY - JOUR

T1 - Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

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

Y1 - 2022/12

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

U2 - 10.1038/s41698-022-00335-y

DO - 10.1038/s41698-022-00335-y

M3 - Article

AN - SCOPUS:85145228241

SN - 2397-768X

VL - 6

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

Abstract

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Field of Science*

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