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Sci. Signal., 29 January 2013
Vol. 6, Issue 260, p. ra7
[DOI: 10.1126/scisignal.2003057]

RESEARCH ARTICLES

Editor's Summary

Stressing Out Resistance
Many melanomas harbor a form of the kinase BRAF with an amino acid substitution (V600E) that renders the protein constitutively active. The mutant BRAF drives cancer growth by activating extracellular signal–regulated kinase (ERK), which promotes cell proliferation and survival. The BRAFV600E kinase inhibitor vemurafenib is initially an effective therapy for melanoma but loses its efficacy because the tumor cells become drug-resistant. Beck et al. found that vemurafenib inhibited survival signaling mediated by ERK and induced endoplasmic reticulum (ER) stress, a form of cellular stress that can culminate in apoptosis. Combined application of vemurafenib with the ER stress inducer thapsigargin to BRAFV600E melanoma cell lines that were resistant to vemurafenib resulted in an enhanced ER stress response and apoptosis. Their findings indicate a potential strategy to overcome drug resistance in BRAF-mutated melanoma.

Citation: D. Beck, H. Niessner, K. S. M. Smalley, K. Flaherty, K. H. T. Paraiso, C. Busch, T. Sinnberg, S. Vasseur, J. L. Iovanna, S. Drießen, B. Stork, S. Wesselborg, M. Schaller, T. Biedermann, J. Bauer, K. Lasithiotakis, B. Weide, J. Eberle, B. Schittek, D. Schadendorf, C. Garbe, D. Kulms, F. Meier, Vemurafenib Potently Induces Endoplasmic Reticulum Stress–Mediated Apoptosis in BRAFV600E Melanoma Cells. Sci. Signal. 6, ra7 (2013).

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