Targeting Mnks for cancer therapy

Jinqiang Hou, Frankie Lam, Christopher Proud, Shudong Wang

Research output: Contribution to journalReview article

106 Citations (Scopus)

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.

LanguageEnglish
Pages118-131
Number of pages14
JournalOncotarget
Volume3
Issue number2
DOIs
Publication statusPublished - 1 Jan 2012
Externally publishedYes

Keywords

  • Akt
  • MAPK
  • Mnk
  • Mnk inhibitors
  • Pi3K
  • Raf
  • Ras
  • Structure based drug design
  • Targeted cancer therapy
  • eIF4E
  • mTOR

ASJC Scopus subject areas

  • Oncology

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