Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules.

doi:10.1158/0008-5472.CAN-20-2929

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Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules.

Cancer research - 15 Apr 2021

Singh Kamini, Lin Jianan, Lecomte Nicolas, Mohan Prathibha, Gokce Askan, Sanghvi Viraj R, Jiang Man, Grbovic-Huezo Olivera, Burčul Antonija, Stark Stefan G, Romesser Paul B, Chang Qing, Melchor Jerry P, Beyer Rachel K, Duggan Mark, Fukase Yoshiyuki, Yang Guangli, Ouerfelli Ouathek, Viale Agnes, de Stanchina Elisa, Stamford Andrew W, Meinke Peter T, Rätsch Gunnar, Leach Steven D, Ouyang Zhengqing, Wendel Hans-Guido

Abstract excerpt

Pancreatic adenocarcinoma (PDAC) epitomizes a deadly cancer driven by abnormal KRAS signaling. Here, we show that the eIF4A RNA helicase is required for translation of key KRAS signaling molecules and that pharmacological inhibition of eIF4A has single-agent activity against murine and human PDAC models at safe dose levels. EIF4A was uniquely required for the translation of mRNAs with long and highly structured...

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Identifiers

PMID: 33632898
DOI: 10.1158/0008-5472.CAN-20-2929
PMCID: PMC8137674

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