Targeting Heat Shock Proteins in Cancer

Cancer Lett. 2013 May 28;332(2):275-85. doi: 10.1016/j.canlet.2010.10.014. Epub 2010 Nov 13.

Abstract

Heat shock proteins (HSPs) HSP27, HSP70 and HSP90 are powerful chaperones. Their expression is induced in response to a wide variety of physiological and environmental insults including anti-cancer chemotherapy, thus allowing the cell to survive to lethal conditions. Different functions of HSPs have been described to account for their cytoprotective function, including their role as molecular chaperones as they play a central role in the correct folding of misfolded proteins, but also their anti-apoptotic properties. HSPs are often overexpressed in cancer cells and this constitutive expression is necessary for cancer cells' survival. HSPs may have oncogene-like functions and likewise mediate "non-oncogene addiction" of stressed tumor cells that must adapt to a hostile microenvironment, thereby becoming dependent for their survival on HSPs. HSP-targeting drugs have therefore emerged as potential anti-cancer agents. This review describes the different molecules and approaches being used or proposed in cancer therapy based on the in inhibition of HSP90, HSP70 and HSP27.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Cell Survival
  • Drug Resistance, Neoplasm
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP90 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Molecular Chaperones / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Protein Conformation
  • Protein Folding

Substances

  • Antineoplastic Agents
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Molecular Chaperones