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Melanoma NRAS - Cooperative induction of apoptosis in nras mutant melanoma by inhibition of mek and rock

ABSTRACT: In the present work we propose a new therapy for NRAS mutant melanoma. Simultaneous inhibition of MEK and ROCK caused induction of BimEL , PARP, and Puma, and hence apoptosis. In vivo, MEK and ROCK inhibition suppressed growth of established tumors. Our findings warrant clinical investigation of the effectiveness of combinatorial targeting of MAPK/ERK and ROCK in NRAS mutant melanoma.

INSTRUMENT(S): LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Whole Body

SUBMITTER: Teck Yew Low

LAB HEAD: Albert J.R. Heck

PROVIDER: PXD000528 | Pride | 2015-03-11

REPOSITORIES: Pride

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Cooperative induction of apoptosis in NRAS mutant melanoma by inhibition of MEK and ROCK.

Vogel Celia J CJ Smit Marjon A MA Maddalo Gianluca G Possik Patricia A PA Sparidans Rolf W RW van der Burg Sjoerd H SH Verdegaal Els M EM Heck Albert J R AJ Samatar Ahmed A AA Beijnen Jos H JH Altelaar A F Maarten AF Peeper Daniel S DS

Pigment cell & melanoma research 20150406 3

No effective targeted therapy is currently available for NRAS mutant melanoma. Experimental MEK inhibition is rather toxic and has only limited efficacy in clinical trials. At least in part, this is caused by the emergence of drug resistance, which is commonly seen for single agent treatment and shortens clinical responses. Therefore, there is a dire need to identify effective companion drug targets for NRAS mutant melanoma. Here, we show that at concentrations where single drugs had little effe ...[more]

PMID: 25728708

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