Targeting Mnks for cancer therapy
Hou, Jinqiang, Lam, Frankie, Proud, Christopher and Wang, Shudong (2012) Targeting Mnks for cancer therapy. Oncotarget, 3, (2), 118-131. (PMID:22392765).
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Description/Abstract
Deregulation of protein synthesis is a common event in human cancer and a key player in translational control is eIF4E. Elevated expression levels of eIF4E promote cancer development and progression. Recent findings suggest that eIF4E activity is a key determinant of the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK mediated tumorigenic activity and targeting eIF4E should have a major impact on these pathways in human cancer. The function of eIF4E is modulated through phosphorylation of a conserved serine (Ser209) by Mnk1 and Mnk2 downstream of ERK. While the phosphorylation event is necessary for oncogenic transformation, it seems to be dispensable for normal development. Hence, pharmacologic Mnk inhibitors may provide non-toxic and effective anti-cancer strategy. Strong circumstantial evidence indicates that Mnk inhibition presents attractive therapeutic potential, but the lack of selective Mnk inhibitors has so far confounded pharmacological target validation and clinical development.
| Item Type: | Article |
|---|---|
| ISSNs: | 1949-2553 (electronic) |
| Related URLs: | |
| Keywords: | eIF4E, Mnk, Ras, Raf, MAPK, Akt, PI3K, mTOR, targeted cancer therapy, structure based drug design, Mnk inhibitors |
| Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Natural and Environmental Sciences > Biological Sciences > Molecular & Cellular |
| Item ID: | 337174 |
| Date Deposited: | 20 Apr 2012 09:24 |
| Last Modified: | 19 Mar 2013 11:27 |
| Contributors: | Hou, Jinqiang (Author) Lam, Frankie (Author) Proud, Christopher (Author) Wang, Shudong (Author) |
| Date: | February 2012 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/337174 |
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