npj Precision Oncology (Dec 2022)
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
Affiliations
- Heike Peterziel
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Nora Jamaladdin
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Dina ElHarouni
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Xenia F. Gerloff
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Sonja Herter
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Petra Fiesel
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Yannick Berker
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Mirjam Blattner-Johnson
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Kathrin Schramm
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Barbara C. Jones
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- David Reuss
- Department Neuropathology at Institute of Pathology, Heidelberg University Hospital
- Laura Turunen
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki
- Aileen Friedenauer
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Tim Holland-Letz
- Division of Biostatistics, German Cancer Research Center (DKFZ)
- Martin Sill
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Lena Weiser
- Core Facility Omics IT and Data Management (ODCF), German Cancer Research Center (DKFZ)
- Christopher Previti
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Gnanaprakash Balasubramanian
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Nicolas U. Gerber
- Department of Oncology, University Children’s Hospital Zürich
- Johannes Gojo
- Department of Pediatrics and Adolescent Medicine, Comprehensive Cancer Center and Comprehensive Center for Pediatrics, Medical University of Vienna
- Caroline Hutter
- St. Anna Children’s Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna
- Ingrid Øra
- Children’s Hospital, Pediatric Oncology, Skåne University Hospital, Lund & Karolinska University Hospital
- Olli Lohi
- Faculty of Medicine and Health Technology, Tampere Center for Child Health Research, Tampere University, Tampere, Finland, and Tays Cancer Center, Tampere University Hospital
- Antonis Kattamis
- First Department of Pediatrics, National and Kapodistrian University of Athens
- Bram de Wilde
- Center for Medical Genetics, Ghent University
- Frank Westermann
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Stephan Tippelt
- Pediatrics III Pediatric Hematology, Oncology, Immunology, Cardiology, Pulmonology, West German Cancer Center; German Cancer Consortium (DKTK), University Hospital Essen
- Norbert Graf
- Department of Pediatric Oncology, Saarland University Medical Center
- Michaela Nathrath
- Department of Pediatric Oncology, Klinikum Kassel
- Monika Sparber-Sauer
- Klinikum der Landeshauptstadt Stuttgart gKAöR, Olgahospital, Stuttgart Cancer Center, Zentrum für Kinder-, Jugend- und Frauenmedizin, Pädiatrie 5 (Pädiatrische Onkologie, Hämatologie, Immunologie)
- Astrid Sehested
- Department of Pediatrics and Adolescent Medicine
- Christof M. Kramm
- Division of Pediatric Hematology and Oncology, University Medical Center Göttingen
- Uta Dirksen
- Pediatrics III Pediatric Hematology, Oncology, Immunology, Cardiology, Pulmonology, West German Cancer Center; German Cancer Consortium (DKTK), University Hospital Essen
- Olli Kallioniemi
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki
- Stefan M. Pfister
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Cornelis M. van Tilburg
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- David T. W. Jones
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Jani Saarela
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki
- Vilja Pietiäinen
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki
- Natalie Jäger
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Matthias Schlesner
- Bioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ)
- Annette Kopp-Schneider
- Division of Biostatistics, German Cancer Research Center (DKFZ)
- Sina Oppermann
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Till Milde
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Olaf Witt
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Ina Oehme
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- DOI
- https://doi.org/10.1038/s41698-022-00335-y
- Journal volume & issue
-
Vol. 6,
no. 1
pp. 1 – 17
Abstract
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.
