Inhibition of HSP90 molecular chaperones: moving into the clinic

Lancet Oncol. 2013 Aug;14(9):e358-69. doi: 10.1016/S1470-2045(13)70169-4.


Heat shock protein 90 (HSP90) is a molecular chaperone that is crucial for the stability and function of many proteins essential for cell survival. Many oncogenes, including tyrosine kinases, transcription factors, and cell-cycle regulatory proteins, are client proteins of HSP90. Inhibition of HSP90 causes client protein degradation via the ubiquitin-proteasome pathway, and is a mechanism that might simultaneously downregulate several redundant pathways crucial for cell viability and tumour development. HSP90 inhibitors are currently being developed as anticancer agents, and have shown early promising results in molecularly defined subgroups of solid tumours (eg, ALK-rearranged non-small-cell lung cancer and HER2-amplified breast cancer) and some haematological malignancies (eg, multiple myeloma). Here, we review the current status of HSP90 inhibitors in clinical development, including geldanamycin derivatives, resorcinol derivatives, purine analogues, and other synthetic inhibitors. We also discuss novel strategies and future perspectives on how to optimise the therapeutic potential of this exciting new class of drugs.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans
  • Molecular Chaperones / antagonists & inhibitors*
  • Neoplasms / drug therapy*


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