The heat shock protein 90 chaperone complex: An evolving therapeutic target Journal Article
| Authors: | Barginear, M. F.; Van Poznak, C.; Rosen, N.; Modi, S.; Hudis, C. A.; Budman, D. R. |
| Article Title: | The heat shock protein 90 chaperone complex: An evolving therapeutic target |
| Abstract: | Hsp90 (heat shock protein 90) is a molecular chaperone that modulates the stability and/or transport of a diverse set of critical cellular regulatory, metabolism, organization, and signaling proteins. Binding to Hsp90 is required for normal function of many proteins. In addition, Hsp90 has an extra-cellular function. It is found in two isotypes: α which is inducible and β which is constitutive. Tumor cells frequently over express Hsp90α, and Hsp90 is implicated in cancer progression. Hence Hsp90 has emerged as a potential target for cancer treatment. A variety of agents have been found to interfere with Hsp function, mainly by binding to an ATP binding site on the molecule. More recent agents interfere with protein binding or the dimerization of Hsp90 needed for function. Preclinical studies have demonstrated that disruption of the many client proteins chaperoned by Hsp90 is achievable and associated with significant growth inhibition, both in vitro and in tumor xenografts. As a result, agents which interfere with this protein's function are being tested in the clinic as a targeted method of interfering with malignant growth. We review the current clinical status of therapeutic efforts to perturb this pathway and discuss future directions. © 2008 Bentham Science Publishers Ltd. |
| Keywords: | osteosarcoma; signal transduction; mitogen activated protein kinase; protein expression; leukemia; unclassified drug; review; advanced cancer; nonhuman; solid tumor; bone metastasis; drug targeting; alpha interferon; pancreas cancer; glioma; protein conformation; protein function; neoplasms; colorectal cancer; animals; gastrointestinal stromal tumor; imatinib; unindexed drug; cancer immunotherapy; melanoma; metastasis; multiple myeloma; ovary cancer; breast cancer; protein protein interaction; epidermal growth factor receptor 2; granulocyte macrophage colony stimulating factor; protein binding; transcription factor; antineoplastic activity; cancer cell culture; tumor xenograft; inhibitor; protein serine threonine kinase; protein p53; cancer therapy; kidney carcinoma; prostate cancer; nonhodgkin lymphoma; immunotherapy; cancer vaccine; neuroblastoma; uterine cervix cancer; protein transport; tumor cell; tanespimycin; heat shock protein 90; hsp90 heat-shock proteins; tamoxifen; stomach cancer; androgen receptor; purine derivative; thyroid cancer; bcr abl protein; protein folding; tumor growth; synovial sarcoma; estrogen receptor; protein structure; antineoplastic antibiotic; macrolide; protein kinase; clinical trials; nitric oxide synthase; growth inhibition; tanespimycin hydroquinone; geldanamycin; radicicol; hsp90; chaperone; ansamycin derivative; janus kinase 1; herbimycin a; kf 58333; novobiocin |
| Journal Title: | Current Cancer Drug Targets |
| Volume: | 8 |
| Issue: | 6 |
| ISSN: | 1568-0096 |
| Publisher: | Bentham Science Publishers |
| Date Published: | 2008-09-01 |
| Start Page: | 522 |
| End Page: | 535 |
| Language: | English |
| DOI: | 10.2174/156800908785699379 |
| PUBMED: | 18781898 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 25" - "Export Date: 17 November 2011" - "CODEN: CCDTB" - "Source: Scopus" |
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