Interferon α/β Enhances the Cytotoxic Response of MEK Inhibition in Melanoma

Oren Litvin, Sarit Schwartz, Zhenmao Wan, Tanya Schild, Mark Rocco, NulLoren Oh, Bo Juen Chen, Noel Goddard, Christine Pratilas, Dana Pe'er

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)784-796
Number of pages13
JournalMolecular Cell
Volume57
Issue number5
DOIs
Publication statusPublished - Mar 5 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Litvin, O., Schwartz, S., Wan, Z., Schild, T., Rocco, M., Oh, N., ... Pe'er, D. (2015). Interferon α/β Enhances the Cytotoxic Response of MEK Inhibition in Melanoma. Molecular Cell, 57(5), 784-796. https://doi.org/10.1016/j.molcel.2014.12.030