In vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer.
drug screen
patient-derived xenograft
pediatric cancer
precision medicine
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 04 2022
07 04 2022
Historique:
revised:
25
11
2021
received:
28
05
2021
accepted:
01
12
2021
pubmed:
21
12
2021
medline:
9
4
2022
entrez:
20
12
2021
Statut:
ppublish
Résumé
Biomarkers which better match anticancer drugs with cancer driver genes hold the promise of improved clinical responses and cure rates. We developed a precision medicine platform of rapid high-throughput drug screening (HTS) and patient-derived xenografting (PDX) of primary tumor tissue, and evaluated its potential for treatment identification among 56 consecutively enrolled high-risk pediatric cancer patients, compared with conventional molecular genomics and transcriptomics. Drug hits were seen in the majority of HTS and PDX screens, which identified therapeutic options for 10 patients for whom no targetable molecular lesions could be found. Screens also provided orthogonal proof of drug efficacy suggested by molecular analyses and negative results for some molecular findings. We identified treatment options across the whole testing platform for 70% of patients. Only molecular therapeutic recommendations were provided to treating oncologists and led to a change in therapy in 53% of patients, of whom 29% had clinical benefit. These data indicate that in vitro and in vivo drug screening of tumor cells could increase therapeutic options and improve clinical outcomes for high-risk pediatric cancer patients.
Identifiants
pubmed: 34927798
doi: 10.15252/emmm.202114608
pmc: PMC8988207
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14608Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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