Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems.
functional screening
pancreatic cancer
precision oncology
therapy-induced vulnerabilities
tumor cell plasticity
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:
12
01
2022
received:
19
07
2021
accepted:
13
01
2022
pubmed:
5
2
2022
medline:
9
4
2022
entrez:
4
2
2022
Statut:
ppublish
Résumé
Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in pancreatic ductal adenocarcinoma (PDAC) is currently neglectable. We present a longitudinal precision oncology platform based on functional model systems, including patient-derived organoids, to identify chemotherapy-induced vulnerabilities. We demonstrate that treatment-induced tumor cell plasticity in vivo distinctly changes responsiveness to targeted therapies, without the presence of a selectable genetic marker, indicating that tumor cell plasticity can be functionalized. By adding a mechanistic layer to precision oncology, adaptive processes of tumors under therapy can be exploited, particularly in highly plastic tumors, such as pancreatic cancer.
Identifiants
pubmed: 35119792
doi: 10.15252/emmm.202114876
pmc: PMC8988213
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14876Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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