Interferon α/β enhances the cytotoxic response of MEK inhibition in melanoma Journal Article


Authors: Litvin, O.; Schwartz, S.; Wan, Z.; Schild, T.; Rocco, M.; Oh, N.; Chen, B. J.; Goddard, N.; Pratilas, C.; Pe'er, D.
Article Title: Interferon α/β enhances the cytotoxic response of MEK inhibition in melanoma
Abstract: Drugs that inhibit the MAPK pathway have therapeutic benefit in melanoma, but responses vary between patients, for reasons that are still largely unknown. Here we aim at explaining this variability using pre- and post-MEK inhibition transcriptional profiles in a panel of melanoma cell lines. We found that most targets are context specific, under the influence of the pathway in only a subset of cell lines. We developed a computational method to identify context-specific targets, and found differences in the activity levels of the interferon pathway, driven by a deletion of the interferon locus. We also discovered that IFNα/β treatment strongly enhances the cytotoxic effect of MEK inhibition, but only in cell lines with low activity of interferon pathway. Taken together, our results suggest that the interferon pathway plays an important role in, and predicts, the response to MAPK inhibition in melanoma. Our analysis demonstrates the value of system-wide perturbation data in predicting drug response. © 2015 Elsevier Inc.
Keywords: signal transduction; controlled study; protein expression; gene cluster; human cell; alpha interferon; protein analysis; melanoma; apoptosis; gene expression; cell growth; genetic variability; antineoplastic activity; nucleotide sequence; melanoma cell; upregulation; beta interferon; n (2,3 dihydroxypropoxy) 3,4 difluoro 2 (2 fluoro 4 iodoanilino)benzamide; rantes; interferon regulatory factor 7; human; article; interferon regulatory factor 9
Journal Title: Molecular Cell
Volume: 57
Issue: 5
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2015-03-05
Start Page: 784
End Page: 796
Language: English
DOI: 10.1016/j.molcel.2014.12.030
PROVIDER: scopus
PMCID: PMC4355234
PUBMED: 25684207
DOI/URL:
Notes: Export Date: 2 April 2015 -- Source: Scopus
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