Work

Chemical Probes for Studying the Eukaryotic Translation Initiation Factor 4E (eIF4E)-Regulated Translatome in Cancer

Year: 2025

Type: review

Abstract: GpppX cap structure at the 5' end of mRNAs to initiate cap-dependent translation. eIF4E is the rate-limiting factor of translation initiation, and its overexpression is known to drive oncogenic transformation, progression, and chemoresistance across many cancers, establishing it as an attractive therapeutic target. Over the last several decades, significant efforts have been made to inhibit eIF4E through the development of mechanistically distinct small-molecule inhibitors that both directly and indirectly act on eIF4E to prevent cap-dependent translation initiation. These inhibitors can serve as powerful chemical tools to improve our understanding of the mechanisms of cap-dependent translation in cancer and to ultimately predict specific cancers that may benefit from eIF4E-targeted therapeutics. This review discusses the progress made in the development of different classes of small-molecule eIF4E inhibitors, the challenges that remain, and their potential as chemical probes to elucidate the complexities of cap-dependent translation in cancer.

Source: ACS Pharmacology & Translational Science

DOI: 10.1021/acsptsci.4c00674

Authors: Rachel L. O’Rourke, Amanda L. Garner

Institution: University of Michigan

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of General Medical Sciences