Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas

Authors

• Edward J Hartsough
• Curtis H Kugel
• Michael J Vido
• Adam C Berger
• Timothy J Purwin
• Allison Goldberg
• Michael A Davies
• Matthew J Schiewer
• Karen E Knudsen
• Gideon Bollag
• Andrew E Aplin

Publication/Presentation Date

1-1-2018

Abstract

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts.

Volume

17

Issue

1

First Page

84

Last Page

95

ISSN

1538-8514

Published In/Presented At

Hartsough, E. J., Kugel, C. H., 3rd, Vido, M. J., Berger, A. C., Purwin, T. J., Goldberg, A., Davies, M. A., Schiewer, M. J., Knudsen, K. E., Bollag, G., & Aplin, A. E. (2018). Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas In Vivo and Ex Vivo. Molecular cancer therapeutics, 17(1), 84–95. https://doi.org/10.1158/1535-7163.MCT-17-0705

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

29133617

Department(s)

Administration and Leadership

Document Type

Article