Interferon α/ß Enhances the Cytotoxic Response of MEK Inhibition in Melanoma.
Mol Cell
; 57(5): 784-796, 2015 Mar 05.
Article
en En
| MEDLINE
| ID: mdl-25684207
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/ß 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
/
Interferón beta
/
Interferón-alfa
/
Sistema de Señalización de MAP Quinasas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos