Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs

Leukemia. 2002 Apr;16(4):455-62. doi: 10.1038/sj.leu.2402415.


Geldanamycin (GA), herbimycin A and radicicol bind heat-shock protein-90 (Hsp90) and destabilize its client proteins including v-Src, Bcr-Abl, Raf-1, ErbB2, some growth factor receptors and steroid receptors. Thus, Hsp90-active agents induce ubiquitination and proteasomal degradation of numerous oncoproteins. Depending on the cellular context, HSP90-active agents cause growth arrest, differentiation and apoptosis, or can prevent apoptosis. HSP-active agents are undergoing clinical trials. Like targets of most chemotherapeutics, Hsp90 is not a cancer-specific protein. By attacking a nonspecific target, HSP-90-active compounds still may preferentially kill certain tumor cells. How can this be achieved? How can therapeutic potentials be exploited? This article starts the discussion.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Benzoquinones
  • Clinical Trials as Topic
  • Growth Inhibitors / pharmacology
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans
  • Lactams, Macrocyclic
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Oncogene Proteins / metabolism*
  • Protein Kinases / metabolism
  • Quinones / pharmacology*
  • Receptors, Growth Factor / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism


  • Antibiotics, Antineoplastic
  • Benzoquinones
  • Growth Inhibitors
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Oncogene Proteins
  • Quinones
  • Receptors, Growth Factor
  • Transcription Factors
  • Protein Kinases
  • geldanamycin