Targeting Oncogene mRNA Translation in B-Cell Malignancies with eFT226, a Potent and Selective Inhibitor of eIF4A.

Animals Biomarkers, Tumor / metabolism Cell Line, Tumor Drug Resistance, Neoplasm / drug effects Eukaryotic Initiation Factor-4A / antagonists & inhibitors Female Humans Lymphoma, B-Cell / genetics Mice, Inbred NOD Mice, SCID Oncogenes PTEN Phosphohydrolase / metabolism Protein Biosynthesis / genetics RNA, Messenger / genetics TOR Serine-Threonine Kinases / metabolism Xenograft Model Antitumor Assays

Journal

Molecular cancer therapeutics

ISSN: 1538-8514

Titre abrégé: Mol Cancer Ther

Pays: United States

ID NLM: 101132535

Informations de publication

Date de publication:
01 2021

Historique:

received: 10 10 2019

revised: 14 02 2020

accepted: 30 09 2020

pubmed: 11 10 2020

medline: 13 8 2021

entrez: 10 10 2020

Statut: ppublish

Résumé

The PI3K/AKT/mTOR pathway is often activated in lymphoma through alterations in PI3K, PTEN, and B-cell receptor signaling, leading to dysregulation of eIF4A (through its regulators, eIF4B, eIF4G, and PDCD4) and the eIF4F complex. Activation of eIF4F has a direct role in tumorigenesis due to increased synthesis of oncogenes that are dependent on enhanced eIF4A RNA helicase activity for translation. eFT226, which inhibits translation of specific mRNAs by promoting eIF4A1 binding to 5'-untranslated regions (UTR) containing polypurine and/or G-quadruplex recognition motifs, shows potent antiproliferative activity and significant

Identifiants

DOI: 10.1158/1535-7163.MCT-19-0973 PMID: 33037136

pubmed: 33037136

pii: 1535-7163.MCT-19-0973

doi: 10.1158/1535-7163.MCT-19-0973

doi:

Substances chimiques

Biomarkers, Tumor 0

RNA, Messenger 0

TOR Serine-Threonine Kinases EC 2.7.11.1

Eukaryotic Initiation Factor-4A EC 2.7.7.-

PTEN Phosphohydrolase EC 3.1.3.67

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

26-36

Informations de copyright

Références

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