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Comment
. 2012 Jan 17;21(1):7-9.
doi: 10.1016/j.ccr.2011.12.017.

How to fool a wonder drug: truncate and dimerize

Miriam Molina-Arcas  1 , Julian Downward
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Free article
Comment

How to fool a wonder drug: truncate and dimerize

Miriam Molina-Arcas et al. Cancer Cell. .
Free article

Abstract

In a recent paper, Poulikakos et al. describe a new and potentially common mechanism whereby melanomas develop resistance to the BRAF inhibitor vemurafenib by expressing truncated forms of BRAF(V600E) that can dimerize in the absence of activated RAS. Will it be possible to block this with improved BRAF inhibitor design?

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  • RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E).
    Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, Shi H, Atefi M, Titz B, Gabay MT, Salton M, Dahlman KB, Tadi M, Wargo JA, Flaherty KT, Kelley MC, Misteli T, Chapman PB, Sosman JA, Graeber TG, Ribas A, Lo RS, Rosen N, Solit DB. Poulikakos PI, et al. Nature. 2011 Nov 23;480(7377):387-90. doi: 10.1038/nature10662. Nature. 2011. PMID: 22113612 Free PMC article.

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