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10:27
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Targeting Mnks for cancer therapy.
Jinqiang Hou1, Frankie Lam, Christopher Proud
1School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
Oncotarget
|March 7, 2012
Summary
Targeting eukaryotic initiation factor 4E (eIF4E) offers a promising anti-cancer strategy. Inhibiting Mnk kinases, which phosphorylate eIF4E, may effectively combat human cancers with reduced toxicity.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Deregulation of protein synthesis, particularly involving eukaryotic initiation factor 4E (eIF4E), is crucial in human cancer development and progression.
- eIF4E activity significantly influences tumorigenic pathways like PI3K/Akt/mTOR and Ras/Raf/MEK/ERK.
Purpose of the Study:
- To explore the therapeutic potential of targeting eIF4E phosphorylation by Mnk1 and Mnk2 as an anti-cancer strategy.
- To evaluate Mnk inhibitors as a potential non-toxic and effective treatment for human cancers.
Main Methods:
- Investigated the role of eIF4E phosphorylation at Ser209 by Mnk1/Mnk2, downstream of ERK signaling.
- Assessed the necessity of this phosphorylation event for oncogenic transformation versus normal development.
Main Results:
- Phosphorylation of eIF4E by Mnk kinases is essential for oncogenic transformation but dispensable for normal development.
- Pharmacological inhibition of Mnk kinases presents a potential anti-cancer strategy.
Conclusions:
- Mnk inhibition is a promising therapeutic avenue for human cancers driven by eIF4E deregulation.
- The lack of selective Mnk inhibitors has hindered clinical development and target validation.
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