Journal Article DKFZ-2022-00383

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png
Functional Therapeutic Target Validation Using Pediatric Zebrafish Xenograft Models.

 ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;

2022
MDPI Basel

Cancers 14(3), 849 () [10.3390/cancers14030849]
 GO

This record in other databases:  

Please use a persistent id in citations: doi:

Abstract: 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.

Keyword(s): drug screen ; functional precision oncology ; mPDX ; patient-derived spheroid culture ; small molecule inhibitors ; targeted therapy ; zPDX

Classification:

Note: #EA:B310#LA:B310#

Contributing Institute(s):
  1. KKE Pädiatrische Onkologie (B310)
  2. DKTK HD zentral (HD01)
  3. B240 Bioinformatik und Omics Data Analytics (B240)
  4. B062 Pädiatrische Neuroonkologie (B062)
  5. NWG Weichteil-Sarkome (B380)
  6. B087 Neuroblastom Genomik (B087)
  7. Lichtmikroskopie (W210)
  8. KKE Neuropathologie (B300)
  9. Pediatric Glioma (B360)
Research Program(s):
  1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2022
Database coverage:
Medline ; Creative Commons Attribution CC BY (No Version) ; DOAJ ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
Click to display QR Code for this record

The record appears in these collections:
Document types > Articles > Journal Article
Public records
Publications database

 Record created 2022-03-01, last modified 2024-02-29


Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)