Analysis and modeling of cancer drug responses using cell cycle phase-specific rate effects.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 06 2023
10 06 2023
Historique:
received:
18
10
2021
accepted:
29
05
2023
medline:
12
6
2023
pubmed:
11
6
2023
entrez:
10
6
2023
Statut:
epublish
Résumé
Identifying effective therapeutic treatment strategies is a major challenge to improving outcomes for patients with breast cancer. To gain a comprehensive understanding of how clinically relevant anti-cancer agents modulate cell cycle progression, here we use genetically engineered breast cancer cell lines to track drug-induced changes in cell number and cell cycle phase to reveal drug-specific cell cycle effects that vary across time. We use a linear chain trick (LCT) computational model, which faithfully captures drug-induced dynamic responses, correctly infers drug effects, and reproduces influences on specific cell cycle phases. We use the LCT model to predict the effects of unseen drug combinations and confirm these in independent validation experiments. Our integrated experimental and modeling approach opens avenues to assess drug responses, predict effective drug combinations, and identify optimal drug sequencing strategies.
Identifiants
pubmed: 37301933
doi: 10.1038/s41467-023-39122-z
pii: 10.1038/s41467-023-39122-z
pmc: PMC10257663
doi:
Substances chimiques
Antineoplastic Agents
0
Drug Combinations
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3450Subventions
Organisme : NCI NIH HHS
ID : U54 CA209988
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG008100
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA215709
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA069533
Pays : United States
Organisme : NIH HHS
ID : S10 OD028512
Pays : United States
Informations de copyright
© 2023. The Author(s).
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