PMID- 19414312
OWN - NLM
STAT- MEDLINE
DCOM- 20090625
LR  - 20090505
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 29
IP  - 3
DP  - 2009 Mar
TI  - Inhibition of cancer invasion and metastasis by targeting the molecular chaperone 
      heat-shock protein 90.
PG  - 797-807
AB  - Heat-shock protein 90 (Hsp90) is a molecular chaperone required for the stability 
      and function of numerous oncogenic signaling proteins that determine the 
      hallmarks of cancer. Receptor tyrosine kinases (RTKs) and hypoxia-inducible 
      factor-1 (HIF-1)-mediated pathways, commonly activated in aggressive cancer, 
      potentiate each other and thus efficiently promote cancer invasion and 
      metastasis. Hsp90 inhibitors, by interacting specifically with a single molecule, 
      Hsp90, cause the destabilization and eventual degradation of multiple Hsp90 
      client proteins. These agents impede the cellular processes involved in cancer 
      invasion and metastasis by simultaneously impairing multiple Hsp90-dependent 
      signaling proteins including HIF-1alpha, most RTKs and their hub mediators Src, 
      Raf-1 and Akt. Recently, a fraction of Hsp90 identified on the cell surface has 
      been found to play a crucial role in cancer invasion and metastasis. The 
      first-in-class Hsp90 inhibitor, 17-allylamino-17-demethoxy-geldanamycin, is 
      currently in phase II clinical trials. The potential utility and problems of 
      Hsp90 inhibitors in clinical settings are discussed. A fuller understanding of 
      the roles of Hsp90 in cancer biology and accumulating clinical data on Hsp90 
      inhibitors will guide us toward the goal of optimizing the use of these agents in 
      the clinic.
FAU - Koga, Fumitaka
AU  - Koga F
AD  - Department of Urology, Tokyo Medical and Dental University Graduate School, 
      Bunkyo-ku, Tokyo 113-8519, Japan. f-koga.uro@tmd.ac.jp
FAU - Kihara, Kazunori
AU  - Kihara K
FAU - Neckers, Len
AU  - Neckers L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (HSP90 Heat-Shock Proteins)
SB  - IM
MH  - Clinical Trials as Topic
MH  - HSP90 Heat-Shock Proteins/*antagonists & inhibitors/metabolism
MH  - Humans
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Neoplasms/metabolism/*pathology/*prevention & control
RF  - 98
EDAT- 2009/05/06 09:00
MHDA- 2009/06/26 09:00
CRDT- 2009/05/06 09:00
PHST- 2009/05/06 09:00 [entrez]
PHST- 2009/05/06 09:00 [pubmed]
PHST- 2009/06/26 09:00 [medline]
AID - 29/3/797 [pii]
PST - ppublish
SO  - Anticancer Res. 2009 Mar;29(3):797-807.