Artikel ; Online: Predicting anti-cancer drug combination responses with a temporal cell state network model.
2023 Band 19, Heft 5, Seite(n) e1011082
Abstract: Cancer chemotherapy combines multiple drugs, but predicting the effects of drug combinations on cancer cell proliferation remains challenging, even for simple in vitro systems. We hypothesized that by combining knowledge of single drug dose responses and ...
Abstract | Cancer chemotherapy combines multiple drugs, but predicting the effects of drug combinations on cancer cell proliferation remains challenging, even for simple in vitro systems. We hypothesized that by combining knowledge of single drug dose responses and cell state transition network dynamics, we could predict how a population of cancer cells will respond to drug combinations. We tested this hypothesis here using three targeted inhibitors of different cell cycle states in two different cell lines in vitro. We formulated a Markov model to capture temporal cell state transitions between different cell cycle phases, with single drug data constraining how drug doses affect transition rates. This model was able to predict the landscape of all three different pairwise drug combinations across all dose ranges for both cell lines with no additional data. While further application to different cell lines, more drugs, additional cell state networks, and more complex co-culture or in vivo systems remain, this work demonstrates how currently available or attainable information could be sufficient for prediction of drug combination response for single cell lines in vitro. |
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Mesh-Begriff(e) | Humans ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Neoplasms/drug therapy ; Drug Combinations ; Cell Proliferation ; Cell Line, Tumor |
Chemische Substanzen | Antineoplastic Agents ; Drug Combinations |
Sprache | Englisch |
Erscheinungsdatum | 2023-05-01 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural |
ZDB-ID | 2193340-6 |
ISSN | 1553-7358 ; 1553-734X |
ISSN (online) | 1553-7358 |
ISSN | 1553-734X |
DOI | 10.1371/journal.pcbi.1011082 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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