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

被引：18

作者：

Peterziel, Heike ^{[1
,2
,3
]}

Jamaladdin, Nora ^{[1
,2
,3
,4
]}

ElHarouni, Dina ^{[1
,4
,5
,6
]}

Gerloff, Xenia F. ^{[1
,2
,3
,7
]}

Herter, Sonja ^{[1
,2
,3
,4
]}

Fiesel, Petra ^{[1
,8
]}

Berker, Yannick ^{[1
,2
,3
]}

Blattner-Johnson, Mirjam ^{[1
,9
,10
,11
]}

Schramm, Kathrin ^{[1
,9
,10
,11
]}

Jones, Barbara C. ^{[1
,9
,10
,11
,12
]}

Reuss, David ^{[13
]}

Turunen, Laura ^{[14
]}

Friedenauer, Aileen ^{[1
,2
,3
]}

Holland-Letz, Tim ^{[15
]}

Sill, Martin ^{[1
]}

Weiser, Lena ^{[16
]}

Previti, Christopher ^{[1
,6
,16
]}

Balasubramanian, Gnanaprakash ^{[1
,6
]}

Gerber, Nicolas U. ^{[17
]}

Gojo, Johannes ^{[18
]}

Hutter, Caroline ^{[19
,20
]}

Ora, Ingrid ^{[21
]}

Lohi, Olli ^{[22
]}

Kattamis, Antonis ^{[23
]}

de Wilde, Bram ^{[24
]}

Westermann, Frank ^{[1
,25
]}

Tippelt, Stephan ^{[26
]}

Graf, Norbert ^{[6
,27
]}

Nathrath, Michaela ^{[28
,29
]}

Sparber-Sauer, Monika ^{[30
,31
]}

Sehested, Astrid ^{[32
]}

Kramm, Christof M. ^{[33
]}

Dirksen, Uta

Kallioniemi, Olli ^{[14
,34
]}

Pfister, Stefan M. ^{[6
,12
]}

van Tilburg, Cornelis M. ^{[1
,2
,12
]}

Jones, David T. W. ^{[1
,9
,10
,11
]}

Saarela, Jani

Pietiaeinen, Vilja ^{[34
]}

Jaeger, Natalie ^{[1
,6
]}

Schlesner, Matthias ^{[5
,35
]}

Kopp-Schneider, Annette

Oppermann, Sina ^{[1
,2
,3
]}

Milde, Till ^{[1
,2
,3
,12
]}

Witt, Olaf ^{[1
,2
,3
,12
]}

Oehme, Ina ^{[1
,2
,3
]}

机构：

[1] Hopp Childrens Canc Ctr Heidelberg KiTZ, D-69120 Heidelberg, Germany

[2] German Canc Res Ctr, Clin Cooperat Unit Pediat Oncol, DKFZ & German Canc Consortium DKTK, D-69120 Heidelberg, Germany

[3] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany

[4] Heidelberg Univ, Fac Biosci, D-69120 Heidelberg, Germany

[5] German Canc Res Ctr, Bioinformat & Om Data Analyt, D-69120 Heidelberg, Germany

[6] German Canc Res Ctr, DKFZ & German Canc Consortium DKTK, Div Pediat Neurooncol, D-69120 Heidelberg, Germany

[7] Heidelberg Univ, Fac Math & Comp Sci, D-69120 Heidelberg, Germany

[8] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, German Consortium Translat Canc Res DKTK, D-69120 Heidelberg, Germany

[9] German Canc Res Ctr, German Canc Res Ctr DKFZ, Div Pediat Glioma Res, D-69120 Heidelberg, Germany

[10] German Canc Res Ctr, German Canc Consortium DKTK, Div Pediat Glioma Res, D-69120 Heidelberg, Germany

[11] German Canc Consortium DKTK, D-69120 Heidelberg, Germany

[12] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol Immunol & Pulmonol, D-69120 Heidelberg, Germany

[13] Univ Heidelberg Hosp, Inst Pathol, Dept Neuropathol, D-69120 Heidelberg, Germany

[14] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki 00014, Finland

[15] German Canc Res Ctr, Div Biostat, Heidelberg, Germany

[16] German Canc Res Ctr, Core Facil Om IT & Data Management ODCF, D-69120 Heidelberg, Germany

[17] Univ Childrens Hosp Zurich, Dept Oncol, CH-8032 Zurich, Switzerland

[18] Med Univ Vienna, Comprehens Canc Ctr, Comprehens Ctr Pediat, Dept Pediat & Adolescent Med, A-1090 Vienna, Austria

[19] Med Univ Vienna, Anna Childrens Hosp 7, Dept Pediat & Adolescent Med, A-1090 Vienna, Austria

[20] St Anna Childrens Canc Res Inst CCRI, Vienna, Austria

[21] Skane Univ Hosp, Lund & Karolinska Univ Hosp, Childrens Hosp Pediat Oncol, Stockholm, Sweden

[22] Tampere Univ, Tampere Univ Hosp, Fac Med & Hlth Technol, Tampere Ctr Child Hlth Res, Tampere, Finland

[23] Natl & Kapodistrian Univ Athens, Dept Pediat 1, Athens, Greece

[24] Univ Ghent, Ctr Med Genet, Ghent, Belgium

[25] German Canc Res Ctr, Div Neuroblastoma Genom, Heidelberg, Germany

[26] Univ Hosp Essen, West German Canc Ctr, Pediatr Pediatr Hematol 3, Oncol, Essen, Germany

[27] Saarland Univ Med Ctr, Dept Pediat Oncol, D-66421 Homburg, Germany

[28] Klinikum Kassel, Dept Pediat Oncol, Kassel, Germany

[29] Tech Univ Munich, Childrens Canc Res Ctr, Dept Pediat, Klinikum Rechts Isar, Munich, Germany

[30] Stuttgart Canc Ctr, Zent Kinder, Klinikum Landeshauptstadt Stuttgart gKAoR, Olgahospita,Padiatrie 5 Padiatr Onkol Hamatol Imm, Stuttgart, Germany

[31] Univ Med Tubingen, Tubingen, Germany

[32] Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark

[33] Univ Med Ctr Gottingen, Div Pediat Hematol & Oncol, Gottingen, Germany

[34] Univ Helsinki, iCAN Digital Precis Canc Med Flagship, FI-00014 Helsinki, Finland

[35] Univ Augsburg, Fac Appl Comp Sci, Med Fac, Biomed Informat, Augsburg, Germany

来源：

NPJ PRECISION ONCOLOGY | 2022年 / 6卷 / 01期

关键词：

MEDICINE; MODELS;

D O I：

10.1038/s41698-022-00335-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：17

共 50 条

[1] Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
Peterziel, Heike
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[2] Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
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