Targeting Mnks for cancer therapy
Targeting Mnks for cancer therapy
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.
eIF4E, Mnk, Ras, Raf, MAPK, Akt, PI3K, mTOR, targeted cancer therapy, structure based drug design, Mnk inhibitors
118-131
Hou, Jinqiang
7ad879b7-2ff9-4e03-8009-f878d711c583
Lam, Frankie
f197fe15-7f5e-44aa-89ce-fd10b731556b
Proud, Christopher
e98b395e-8ce8-465c-bbcb-76026acea42b
Wang, Shudong
9816cc9c-3c96-4376-927d-fef61104a87a
February 2012
Hou, Jinqiang
7ad879b7-2ff9-4e03-8009-f878d711c583
Lam, Frankie
f197fe15-7f5e-44aa-89ce-fd10b731556b
Proud, Christopher
e98b395e-8ce8-465c-bbcb-76026acea42b
Wang, Shudong
9816cc9c-3c96-4376-927d-fef61104a87a
Hou, Jinqiang, Lam, Frankie, Proud, Christopher and Wang, Shudong
(2012)
Targeting Mnks for cancer therapy.
Oncotarget, 3 (2), .
(PMID:22392765)
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.
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Published date: February 2012
Keywords:
eIF4E, Mnk, Ras, Raf, MAPK, Akt, PI3K, mTOR, targeted cancer therapy, structure based drug design, Mnk inhibitors
Organisations:
Molecular and Cellular
Identifiers
Local EPrints ID: 337174
URI: http://eprints.soton.ac.uk/id/eprint/337174
ISSN: 1949-2553
PURE UUID: a94780d9-6cee-4c69-964e-a95aa1675d29
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Date deposited: 20 Apr 2012 09:24
Last modified: 22 Jul 2022 18:03
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Contributors
Author:
Jinqiang Hou
Author:
Frankie Lam
Author:
Christopher Proud
Author:
Shudong Wang
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