title: Implications of endoplasmic reticulum stress, the unfolded protein response and apoptosis for molecular cancer therapy. Part I: targeting p53, Mdm2, GADD153/CHOP, GRP78/BiP and heat shock proteins.
abstract: BACKGROUND
  In eukaryotes, endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are coordinately regulated to maintain steady-state levels and activities of various cellular proteins to ensure cell survival.
  
  
  OBJECTIVE
  This review (Part I of II) focuses on specific ERS and UPR signalling regulators, their expression in the cancer phenotype and apoptosis, and proposes how their implication in these processes can be rationalised into proteasome inhibition, apoptosis induction and the development of more efficacious targeted molecular cancer therapies.
  
  
  METHODS
  In this review, we contextualise many ERS and UPR client proteins that are deregulated or mutated in cancers and show links between ERS and the UPR, their implication in oncogenic transformation, tumour progression and escape from immune surveillance, apoptosis inhibition, angiogenesis, metastasis, acquired drug resistance and poor cancer prognosis.
  
  
  CONCLUSIONS
  Evasion of programmed cell death or apoptosis is a hallmark of cancer that enables tumour cells to proliferate uncontrollably. Successful eradication of cancer cells through targeting ERS- and UPR-associated proteins to induce apoptosis is currently being pursued as a central tenet of anticancer drug discovery.
authors.affiliation: Head, Molecular Oncology Research Programme University of the Western Cape, Department of Medical BioSciences, Bellville, 7535, South Africa +27 21 959 2334 ; +27 21 959 1563 ; dhiss@uwc.ac.za.
authors.forename: Donavon C
authors.initials: DC
authors.lastname: Hiss
authors.forename: Gary A
authors.initials: GA
authors.lastname: Gabriels