A modified fluctuation-test framework characterizes the population dynamics and mutation rate of colorectal cancer persister cells.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
27
04
2021
accepted:
25
05
2022
pubmed:
12
7
2022
medline:
16
7
2022
entrez:
11
7
2022
Statut:
ppublish
Résumé
Compelling evidence shows that cancer persister cells represent a major limit to the long-term efficacy of targeted therapies. However, the phenotype and population dynamics of cancer persister cells remain unclear. We developed a quantitative framework to study persisters by combining experimental characterization and mathematical modeling. We found that, in colorectal cancer, a fraction of persisters slowly replicates. Clinically approved targeted therapies induce a switch to drug-tolerant persisters and a temporary 7- to 50-fold increase of their mutation rate, thus increasing the number of persister-derived resistant cells. These findings reveal that treatment may influence persistence and mutability in cancer cells and pinpoint inhibition of error-prone DNA polymerases as a strategy to restrict tumor recurrence.
Identifiants
pubmed: 35817983
doi: 10.1038/s41588-022-01105-z
pii: 10.1038/s41588-022-01105-z
pmc: PMC9279152
doi:
Substances chimiques
Anti-Bacterial Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
976-984Informations de copyright
© 2022. The Author(s).
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