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Perturbation biology links temporal protein changes to drug responses in a melanoma cell line.


ABSTRACT: Cancer cells have genetic alterations that often directly affect intracellular protein signaling processes allowing them to bypass control mechanisms for cell death, growth and division. Cancer drugs targeting these alterations often work initially, but resistance is common. Combinations of targeted drugs may overcome or prevent resistance, but their selection requires context-specific knowledge of signaling pathways including complex interactions such as feedback loops and crosstalk. To infer quantitative pathway models, we collected a rich dataset on a melanoma cell line: Following perturbation with 54 drug combinations, we measured 124 (phospho-)protein levels and phenotypic response (cell growth, apoptosis) in a time series from 10 minutes to 67 hours. From these data, we trained time-

SUBMITTER: Nyman E 

PROVIDER: S-EPMC7384681 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature