Inhibition of HSP70: a challenging anti-cancer strategy

Cancer Lett. 2012 Dec 28;325(2):117-24. doi: 10.1016/j.canlet.2012.06.003. Epub 2012 Jun 28.

Abstract

HSP70 is a chaperone that accumulates in the cells after many different stresses promoting cell survival in response to the adverse conditions. In contrast to normal cells, most cancer cells abundantly express HSP70 at the basal level to resist to various insults at different stages of tumorigenesis and during anti-cancer treatment. This cancer cells addiction for HSP70 is the rational for its targeting in cancer therapy. Much effort has been dedicated in the last years for the active search of HSP70 inhibitors. Additionally, the recent clinical trials on highly promising inhibitors of another stress protein, HSP90, showed compensatory increase in HSP70 levels and raised the question of necessity to combine HSP90 inhibitors with simultaneous inhibition of HSP70. Here we analyzed the recent advancement in creation of novel HSP70 inhibitors and different strategies for their use in anti-cancer therapy.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / physiology
  • Autophagy / physiology
  • Drug Design
  • Drug Resistance, Neoplasm / drug effects
  • Drug Screening Assays, Antitumor
  • HSP70 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / physiology
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • Humans
  • Molecular Chaperones / antagonists & inhibitors
  • Molecular Chaperones / physiology
  • Molecular Targeted Therapy*
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / physiology
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Protein Structure, Tertiary / drug effects
  • Stress, Physiological

Substances

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