The unfolded protein response as a target for cancer therapy

Anika Nagelkerke, Johan Bussink, Fred C G J Sweep, Paul N Span*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

88 Citations (Scopus)


Various physiological and pathological conditions generate an accumulation of misfolded proteins in the endoplasmic reticulum (ER). This results in ER stress followed by a cellular response to cope with this stress and restore homeostasis: the unfolded protein response (UPR). Overall, the UPR leads to general translational arrest and the induction of specific factors to ensure cell survival or to mediate cell death if the stress is too severe. In multiple cancers, components of the UPR are overexpressed, indicating increased dependence on the UPR. In addition, the UPR can confer resistance to anti-cancer treatment. Therefore, modification of the UPR should be explored for its anti-cancer properties. This review discusses factors associated with the UPR that represent potential therapeutic targets.

Original languageEnglish
Pages (from-to)277-84
Number of pages8
JournalBiochimica et biophysica acta
Issue number2
Publication statusPublished - Dec-2014
Externally publishedYes


  • Animals
  • Autophagy
  • Endoplasmic Reticulum Stress/drug effects
  • Endoribonucleases/physiology
  • Heat-Shock Proteins/physiology
  • Humans
  • Neoplasms/drug therapy
  • Protein-Serine-Threonine Kinases/physiology
  • Unfolded Protein Response/drug effects
  • eIF-2 Kinase/physiology


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