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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
Eukaryotic translation initiation factor 4E as a novel therapeutic target in hematological malignancies and beyond
Filippa Pettersson1, Sonia V Del Rincon, Wilson H Miller
1McGill University, Lady Davis Institute for Medical Research, Jewish General Hospital, Segal Cancer Centre , Montreal, Quebec H3T 1E2 , Canada +1 514 340 8222, Ext. 4365 ; +1 514 340 8717 ; wmiller@ldi.jgh.mcgill.ca.
Introduction:
The eukaryotic translation initiation factor 4E (eIF4E) is a key regulator of protein synthesis, and an oncogene. Its expression and activity are frequently elevated in cancer, and have been shown to correlate with poor prognosis. Efforts to target eIF4E have thus yielded much interest, with some clinical success.
Areas Covered:
We provide an overview of eIF4E function and regulation, and its role in hematological malignancies and solid tumors. Activation of eIF4E via upstream signaling pathways that are frequently deregulated in cancer and the role of eIF4E phosphorylation are discussed. We present an updated review of different approaches to target eIF4E function in the lab and in the clinic.
Expert Opinion:
The prospect of effectively targeting eIF4E in cancer is very attractive, because eIF4E is a common downstream node on which multiple oncogenic signaling pathways converge. However, efforts to do so have yielded limited clinical success so far. While active-site inhibitors of mammalian target of rapamycin show some promise, and inhibitors of eIF4E phosphorylation may emerge as clinical candidates, the only drug to date that has demonstrated antitumor activity associated with eIF4E inhibition in patients is ribavirin. Further studies will certainly aid the design of better compounds and rational combination therapies.
Insights
Targeting eukaryotic translation initiation factor 4E (eIF4E), a cancer-driving oncogene, shows promise but has limited clinical success. Ribavirin is the only drug demonstrating antitumor activity via eIF4E inhibition to date.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Eukaryotic translation initiation factor 4E (eIF4E) is a critical regulator of protein synthesis and an oncogene.
- Elevated eIF4E expression and activity are common in cancers, correlating with poor prognosis.
Purpose of the Study:
- To review the function, regulation, and therapeutic targeting of eIF4E in various cancers.
- To discuss upstream signaling pathways and eIF4E phosphorylation in cancer activation.
- To present an updated overview of laboratory and clinical approaches to inhibit eIF4E.
Main Methods:
- Literature review of eIF4E function, regulation, and role in hematological malignancies and solid tumors.
- Discussion of signaling pathways activating eIF4E and its phosphorylation.
- Review of current and emerging strategies for targeting eIF4E.
Main Results:
- Multiple oncogenic signaling pathways converge on eIF4E, making it an attractive therapeutic target.
- Current therapeutic strategies targeting eIF4E have shown limited clinical success.
- Ribavirin is the only drug demonstrating clinical antitumor activity through eIF4E inhibition.
Conclusions:
- Despite challenges, targeting eIF4E remains a highly attractive strategy in cancer therapy.
- Inhibitors of mammalian target of rapamycin (mTOR) and eIF4E phosphorylation show potential.
- Further research is crucial for developing effective eIF4E-targeted compounds and combination therapies.
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