RAF inhibitors that evade paradoxical MAPK pathway activation.

doi:10.1038/nature14982

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Article

RAF inhibitors that evade paradoxical MAPK pathway activation.

Nature - 22 Oct 2015

Zhang Chao, Spevak Wayne, Zhang Ying, Burton Elizabeth A, Ma Yan, Habets Gaston, Zhang Jiazhong, Lin Jack, Ewing Todd, Matusow Bernice, Tsang Garson, Marimuthu Adhirai, Cho Hanna, Wu Guoxian, Wang Weiru, Fong Daniel, Nguyen Hoa, Shi Songyuan, Womack Patrick, Nespi Marika, Shellooe Rafe, Carias Heidi, Powell Ben, Light Emily, Sanftner Laura, Walters Jason, Tsai James, West Brian L, Visor Gary, Rezaei Hamid, Lin Paul S, Nolop Keith, Ibrahim Prabha N, Hirth Peter, Bollag Gideon

Abstract excerpt

Oncogenic activation of BRAF fuels cancer growth by constitutively promoting RAS-independent mitogen-activated protein kinase (MAPK) pathway signalling. Accordingly, RAF inhibitors have brought substantially improved personalized treatment of metastatic melanoma. However, these targeted agents have also revealed an unexpected consequence: stimulated growth of certain cancers. Structurally diverse ATP-competitive...

Topics

Animals
Cell Line, Tumor
Enzyme Activation
Female
Genes, ras
Heterocyclic Compounds, 2-Ring
Humans
Indoles
MAP Kinase Signaling System

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Mice

Mitogen-Activated Protein Kinases

Models, Biological

Mutation

Protein Kinase Inhibitors

Proto-Oncogene Proteins B-raf

Sulfonamides

Vemurafenib

Source

Open in PubMed

Identifiers

PMID: 26466569
DOI: 10.1038/nature14982

Genes

BRAF
HRAS

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 29 Aug 2026. Prepared record publication-26466569-2026-08-29.1. Manifest publication-graph-cohort-2026-08-29.1.

Source receipt: PubMed via Helena Literature Corpus, retrieved 29 Aug 2026.

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