TY  - JOUR
AU  - Gatzweiler, Charlotte
AU  - Ridinger, Johannes
AU  - Herter, Sonja
AU  - Gerloff, Xenia F
AU  - ElHarouni, Dina
AU  - Berker, Yannick
AU  - Imle, Roland
AU  - Schmitt, Lukas
AU  - Kreth, Sina
AU  - Stainczyk, Sabine
AU  - Ayhan, Simay
AU  - Najafi, Sara
AU  - Krunic, Damir
AU  - Frese, Karen
AU  - Meder, Benjamin
AU  - Reuss, David
AU  - Fiesel, Petra
AU  - Schramm, Kathrin
AU  - Blattner-Johnson, Mirjam
AU  - Jones, David T W
AU  - Banito, Ana
AU  - Westermann, Frank
AU  - Oppermann, Sina
AU  - Milde, Till
AU  - Peterziel, Heike
AU  - Witt, Olaf
AU  - Oehme, Ina
TI  - Functional Therapeutic Target Validation Using Pediatric Zebrafish Xenograft Models.
JO  - Cancers
VL  - 14
IS  - 3
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2022-00383
SP  - 849
PY  - 2022
N1  - #EA:B310#LA:B310#
AB  - The survival rate among children with relapsed tumors remains poor, due to tumor heterogeneity, lack of directly actionable tumor drivers and multidrug resistance. Novel personalized medicine approaches tailored to each tumor are urgently needed to improve cancer treatment. Current pediatric precision oncology platforms, such as the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) study, reveal that molecular profiling of tumor tissue identifies targets associated with clinical benefit in a subgroup of patients only and should be complemented with functional drug testing. In such an approach, patient-derived tumor cells are exposed to a library of approved oncological drugs in a physiological setting, e.g., in the form of animal avatars injected with patient tumor cells. We used molecularly fully characterized tumor samples from the INFORM study to compare drug screen results of individual patient-derived cell models in functional assays: (i) patient-derived spheroid cultures within a few days after tumor dissociation; (ii) tumor cells reisolated from the corresponding mouse PDX; (iii) corresponding long-term organoid-like cultures and (iv) drug evaluation with the corresponding zebrafish PDX (zPDX) model. Each model had its advantage and complemented the others for drug hit and drug combination selection. Our results provide evidence that in vivo zPDX drug screening is a promising add-on to current functional drug screening in precision medicine platforms.
KW  - drug screen (Other)
KW  - functional precision oncology (Other)
KW  - mPDX (Other)
KW  - patient-derived spheroid culture (Other)
KW  - small molecule inhibitors (Other)
KW  - targeted therapy (Other)
KW  - zPDX (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:35159116
C2  - pmc:PMC8834194
DO  - DOI:10.3390/cancers14030849
UR  - https://inrepo02.dkfz.de/record/178967
ER  -