HSP90 and the chaperoning of cancer (original) (raw)

• Wegele, H., Muller, L. & Buchner, J. Hsp70 and Hsp90 — a relay team for protein folding. Rev. Physiol. Biochem. Pharmacol. 151, 1–44 (2004).
  Article CAS PubMed Google Scholar
• Takayama, S., Reed, J. C. & Homma, S. Heat-shock proteins as regulators of apoptosis. Oncogene 22, 9041–9047 (2003).
  Article CAS PubMed Google Scholar
• Dymock, B. W., Drysdale, M. J., McDonald, E. & Workman, P. Inhibitors of HSP90 and other chaperones for the treatment of cancer. Expert. Opin. Ther. Patents 14, 837–847 (2004).
  Article CAS Google Scholar
• Morimoto, R. I. & Santoro, M. G. Stress-inducible responses and heat shock proteins: new pharmacologic targets for cytoprotection. Nature Biotechnol. 16, 833–838 (1998).
  Article CAS Google Scholar
• Leppa, S. & Sistonen, L. Heat shock response — pathophysiological implications. Ann. Med. 29, 73–78 (1997).
  Article CAS PubMed Google Scholar
• Jolly, C. & Morimoto, R. I. Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J. Natl. Cancer Inst. 92, 1564–1572 (2000).
  Article CAS PubMed Google Scholar
• Smith, D. F., Whitesell, L. & Katsanis, E. Molecular chaperones: biology and prospects for pharmacological intervention. Pharm. Rev. 50, 493–513 (1998).
  CAS PubMed Google Scholar
• Buchner, J. Hsp90 & Co.—a holding for folding. Trends biochem. Sci. 24, 136–141 (1999).
  Article CAS PubMed Google Scholar
• Csermely, P., Schnaider, T., Soti, C., Prohaskka, Z. & Nardai, G. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol. Ther. 79, 129–168 (1998).
  Article CAS PubMed Google Scholar
• Picard, D. et al. Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature 348, 166–168 (1990).
  Article CAS PubMed Google Scholar
• Freeman, B. C. & Yamamoto, K. R. Disassembly of transcriptional regulatory complexes by molecular chaperones. Science 296, 2232–2235 (2002). Surprising evidence that chaperones not only have a role in regulating the activation of signal transduction pathways, but can also modulate cellular activities by assisting in the termination of transcriptional responses.
  Article CAS PubMed Google Scholar
• Zeng, Y., Feng, H., Graner, M. W. & Katsanis, E. Tumor-derived, chaperone-rich cell lysate activates dendritic cells and elicits potent antitumor immunity. Blood 101, 4485–4491 (2003).
  Article CAS PubMed Google Scholar
• Parmiani, G. et al. Heat shock proteins and their use as anticancer vaccines. Clin. Cancer Res. 10, 8142–8146 (2004).
  Article CAS PubMed Google Scholar
• Smith, D. F. et al. Progesterone receptor structure and function altered by geldanamycin, an hsp90-binding agent. Mol.Cell. Biol. 15, 6804–6812 (1995). Describes the cyclical chaperone interactions that were shown in rabbit reticulocyte lysate to regulate the high affinity binding of hormone by steroid receptors and how this cycling is disrupted by geldanamycin.
  Article CAS PubMed PubMed Central Google Scholar
• Nathan, D. E., Vos, M. H. & Lindquist, S. In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone. Proc. Natl Acad. Sci. USA 94, 12949–12956 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Pratt, W. B. The hsp90-based chaperone system: involvement in signal transduction from a variety of hormone and growth factor receptors. Proc. Soc. Exp. Biol. Med. 217, 420–431 (1998).
  Article CAS PubMed Google Scholar
• Zhao, R. et al. Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone. Cell 120, 715–727 (2005).
  Article CAS PubMed Google Scholar
• Morimoto, R. I. Dynamic remodeling of transcription complexes by molecular chaperones. Cell 110, 281–284 (2002).
  Article CAS PubMed Google Scholar
• Sollars, V. et al. Evidence for an epigenetic mechanism by which Hsp90 acts as a capacitor for morphological evolution. Nature Genet. 33, 70–74 (2003).
  Article CAS PubMed Google Scholar
• Sangster, T. A., Queitsch, C. & Lindquist, S. Hsp90 and chromatin: where is the link? Cell Cycle 2, 166–168 (2003).
  Article CAS PubMed Google Scholar
• Rutherford, S. L. & Lindquist, S. Hsp90 as a capacitor for morphological evolution. Nature 396, 336–342 (1998). Groundbreaking report that the chaperone function of HSP90 can buffer genetic variation in D. melanogaster , allowing it to accumulate silently until it is released in the face of environmental stress to be acted on by natural selection.
  Article CAS PubMed Google Scholar
• Queitsch, C., Sangster, T. A. & Lindquist, S. Hsp90 as a capacitor of phenotypic variation. Nature 417, 618–624 (2002).
  Article CAS PubMed Google Scholar
• Ruden, D. M., Garfinkel, M. D., Sollars, V. E. & Lu, X. Waddington's widget: Hsp90 and the inheritance of acquired characters. Semin. Cell Dev. Biol. 14, 301–310 (2003).
  Article CAS PubMed Google Scholar
• Sangster, T. A., Lindquist, S. & Queitsch, C. Under cover: causes, effects and implications of Hsp90-mediated genetic capacitance. Bioessays 26, 348–362 (2004).
  Article CAS PubMed Google Scholar
• Rutherford, S. L. Between genotype and phenotype: protein chaperones and evolvability. Nature Rev. Genet. 4, 263–274 (2003).
  Article CAS PubMed Google Scholar
• Bagatell, R. & Whitesell, L. Altered Hsp90 function in cancer: a unique therapeutic opportunity. Mol. Cancer Ther. 3, 1021–1030 (2004).
  Article CAS PubMed Google Scholar
• Gatenby, R. A. & Vincent, T. L. An evolutionary model of carcinogenesis. Cancer Res. 63, 6212–6220 (2003).
  CAS PubMed Google Scholar
• Kimura, E. et al. Correlation of the survival of ovarian cancer patients with mRNA expression of the 60kDa heat shock protein Hsp60. J. Clin. Oncol. 11, 891–898 (1993).
  Article CAS PubMed Google Scholar
• Ciocca, D. R. et al. Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. J. Natl Cancer Inst. 85, 570–574 (1993).
  Article CAS PubMed Google Scholar
• Conroy, S. E., Sasieni, P. D., Fentiman, I. & Latchman, D. S. Autoantibodies to the 90kDa heat shock protein and poor survival in breast cancer patients. Eur. J. Cancer 34, 942–943 (1998).
  CAS PubMed Google Scholar
• Ralhan, R. & Kaur, J. Differential expression of Mr 70, 000 heat shock protein in normal, premalignant, and malignant human uterine cervix. Clin. Cancer Res. 1, 1217–1222 (1995).
  CAS PubMed Google Scholar
• Kaur, J. & Ralhan, R. Differential expression of 70-kDa heat shock-protein in human oral tumorigenesis. Int. J. Cancer 63, 774–779 (1995).
  Article CAS PubMed Google Scholar
• Santarosa, M., Favaro, D., Quaia, M. & Galligioni, E. Expression of heat shock protein 72 in renal cell carcinoma: possible role and prognostic implications in cancer patients. Eur. J. Cancer 33, 873–877 (1997).
  Article CAS PubMed Google Scholar
• Chant, I. D., Rose, P. E. & Morris, A. G. Analysis of heat shock protein expression in myeloid leukaemia cells by flow cytometry. Br. J. Haematol. 90, 163–168 (1995).
  Article CAS PubMed Google Scholar
• Yufu, Y., Nishimura, J. & Nawata, H. High constitutive expression of heat shock protein 90α in human acute leukemia cells. Leuk. Res. 16, 597–605 (1992).
  Article CAS PubMed Google Scholar
• Jameel, A. et al. Clinical and biological significance of Hsp90a in human breast cancer. Int. J. Cancer 50, 409–415 (1992).
  Article CAS PubMed Google Scholar
• Yano, M., Naito, Z., Tanaka, S. & Asano, G. Expression and roles of heat shock proteins in human breast cancer. Jpn. J. Cancer Res. 87, 908–915 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Nanbu, K. et al. Prognostic significance of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. Cancer Detect. Prev. 22, 549–555 (1998).
  Article CAS PubMed Google Scholar
• Trieb, K. et al. Antibodies to heat shock protein 90 in osteosarcoma patients correlate with response to neoadjuvant chemotherapy. BR. J. Cancer 82, 85–87 (2000).
  Article CAS PubMed Google Scholar
• Mosser, D. D. & Morimoto, R. I. Molecular chaperones and the stress of oncogenesis. Oncogene 23, 2907–2918 (2004).
  Article CAS PubMed Google Scholar
• Jaattela, M. Escaping cell death: survival proteins in cancer. Exp. Cell Res. 248, 30–43 (1999).
  Article CAS PubMed Google Scholar
• Hannun, Y. Apoptosis and the dilemma of cancer chemotherapy. Blood 89, 1845–1853 (1997).
  CAS PubMed Google Scholar
• Sliutz, G. et al. Drug resistance against gemcitabine and topotecan mediated by constitutive hsp70 overexpression in vitro: implication of quercetin as sensitiser in chemotherapy. Br. J. Cancer 74, 172–177 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Mosser, D. D. et al. The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Mol. Cell. Biol. 20, 7146–7159 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Steel, R. et al. Hsp72 inhibits apoptosis upstream of the mitochondria and not through interactions with Apaf-1. J. Biol. Chem. 279, 51490–51499 (2004).
  Article CAS PubMed Google Scholar
• Mosser, D. D., Caron, A. W., Bourget, L., Denis-Larose, C. & Massie, B. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol. Cell. Biol. 17, 5317–5327 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Nylandsted, J. et al. Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2. Proc. Natl Acad. Sci. USA 97, 7871–7876 (2000). Demonstrates differential requirements for HSP70 in the growth and survival of breast cancer cells compared with normal cells.
  Article CAS PubMed PubMed Central Google Scholar
• Rohde, M. et al. Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms. Genes Dev. 19, 570–582 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Basso, A. D. et al. Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function. J. Biol. Chem. 277, 39858–39866 (2002).
  Article CAS PubMed Google Scholar
• Vanden Berghe, T., Kalai, M., van Loo, G., Declercq, W. & Vandenabeele, P. Disruption of HSP90 function reverts tumor necrosis factor-induced necrosis to apoptosis. J. Biol. Chem. 278, 5622–5629 (2003).
  Article CAS PubMed Google Scholar
• Chen, G., Cao, P. & Goeddel, D. V. TNF-induced recruitment and activation of the IkK complex require Cdc37 and Hsp90. Mol. Cell 9, 401–410 (2002).
  Article CAS PubMed Google Scholar
• Xu, Y., Singer, M. A. & Lindquist, S. Maturation of the tyrosine kinase c-src as a kinase and as a substrate depends on the molecular chaperone Hsp90. Proc. Natl Acad. Sci. USA 96, 109–114 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Oppermann, H., Levinson, W. & Bishop, J. M. A cellular protein that associates with the transforming protein of Rous sarcoma virus is also a heat-shock protein. Proc. Natl Acad. Sci. USA 78, 1067–1071 (1981).
  Article CAS PubMed PubMed Central Google Scholar
• Brugge, J., Yonemoto, W. & Darrow, D. Interaction between the Rous sarcoma virus transforming protein and two cellular phosphoproteins: analysis of the turnover and distribution of this complex. Mol. Cell. Biol. 3, 9–19 (1983).
  Article CAS PubMed PubMed Central Google Scholar
• Xu, Y. & Lindquist, S. Heat-shock protein hsp90 governs the activity of pp60vsrc kinase. Proc. Natl Acad. Sci. USA 90, 7074–7078 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Whitesell, L., Mimnaugh, E. G., De Costa, B., Myers, C. E. & Neckers, L. M. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc. Natl. Acad. Sci. USA 91, 8324–8328 (1994). Identification of geldanamycin as the first small-molecule inhibitor of HSP90 chaperone function.
  Article CAS PubMed PubMed Central Google Scholar
• Muller, L., Schaupp, A., Walerych, D., Wegele, H. & Buchner, J. Hsp90 regulates the activity of wild type p53 under physiological and elevated temperatures. J. Biol. Chem. 279, 48846–48854 (2004).
  Article PubMed CAS Google Scholar
• Walerych, D. et al. Hsp90 chaperones wild-type p53 tumor suppressor protein. J. Biol. Chem. 279, 48836–48845 (2004).
  Article CAS PubMed Google Scholar
• Whitesell, L., Sutphin, P. D., Pulcini, E. J., Martinez, J. D. & Cook, P. H. The physical association of multiple molecular chaperone proteins with mutant p53 is altered by geldanamycin, an hsp90-binding agent. Mol. Cell. Biol. 18, 1517–1524 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Blagosklonny, M. V., Toretsky, J., Bohen, S. & Neckers, L. Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90. Proc. Natl Acad. Sci. USA 93, 8379–8383 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Sepehrnia, B., Paz, I. B., Dasgupta, G. & Momand, J. Heat shock protein 84 forms a complex with mutant p53 protein predominantly within a cytoplasmic compartment of the cell. J. Biol. Chem. 271, 15084–15090 (1996).
  Article CAS PubMed Google Scholar
• Sreedhar, A. S., Kalmar, E., Csermely, P. & Shen, Y. F. Hsp90 isoforms: functions, expression and clinical importance. FEBS Lett. 562, 11–15 (2004).
  Article PubMed CAS Google Scholar
• Eustace, B. K. et al. Functional proteomic screens reveal an essential extracellular role for hsp90 α in cancer cell invasiveness. Nature Cell Biol. 6, 507–514 (2004).
  Article CAS PubMed Google Scholar
• Grammatikakis, N. et al. The role of Hsp90N, a new member of the Hsp90 family, in signal transduction and neoplastic transformation. J. Biol. Chem. 277, 8312–8320 (2002).
  Article CAS PubMed Google Scholar
• Pearl, L. H. & Prodromou, C. Structure, function, and mechanism of the Hsp90 molecular chaperone. Adv. Protein Chem. 59, 157–186 (2001).
  Article CAS PubMed Google Scholar
• Prodromou, C. & Pearl, L. H. Structure and functional relationships of Hsp90. Curr. Cancer Drug Targets 3, 301–323 (2003).
  Article CAS PubMed Google Scholar
• Stebbins, C. E. et al. Crystal structure of an hsp90–geldanamycin complex: targeting of a protein chaperone by an anti-tumor agent. Cell 89, 239–250 (1997).
  Article CAS PubMed Google Scholar
• Prodromou, C. et al. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 90, 65–75 (1997). Identification and characterization of the binding pocket for geldanamycin on HSP90 as an atypical ATPase site.
  Article CAS PubMed Google Scholar
• Meyer, P. et al. Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions. Mol. Cell 11, 647–658 (2003).
  Article CAS PubMed Google Scholar
• Huai, Q. et al. Structures of the N-terminal and middle domains of E. coli Hsp90 and conformation changes upon ADP binding. Structure (Camb) 13, 579–590 (2005).
  Article CAS Google Scholar
• Harris, S. F., Shiau, A. K. & Agard, D. A. The crystal structure of the carboxy-terminal dimerization domain of htpG, the Escherichia coli Hsp90, reveals a potential substrate binding site. Structure (Camb) 12, 1087–1097 (2004).
  Article CAS Google Scholar
• Dutta, R. & Inouye, M. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem. Sci. 25, 24–28 (2000).
  Article CAS PubMed Google Scholar
• McLaughlin, S. H., Ventouras, L. A., Lobbezoo, B. & Jackson, S. E. Independent ATPase activity of Hsp90 subunits creates a flexible assembly platform. J. Mol. Biol. 344, 813–826 (2004). Biophysical evidence for an alternative to the 'molecular clamp' model of HSP90 chaperoning action.
  Article CAS PubMed Google Scholar
• Roe, S. M. et al. The mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37). Cell 116, 87–98 (2004).
  Article CAS PubMed Google Scholar
• Pearl, L. H. Hsp90 and Cdc37 — a chaperone cancer conspiracy. Curr. Opin. Genet. Dev. 15, 55–61 (2005).
  Article CAS PubMed Google Scholar
• Soti, C., Racz, A. & Csermely, P. A nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of Hsp90. J. Biol. Chem. 277, 7066–7075 (2002).
  Article CAS PubMed Google Scholar
• Meyer, P. et al. Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery. Embo J. 23, 511–519 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Panaretou, B. et al. Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1. Mol. Cell 10, 1307–1318 (2002).
  Article CAS PubMed Google Scholar
• Garnier, C. et al. Binding of ATP to heat shock protein 90: evidence for an ATP-binding site in the C-terminal domain. J. Biol. Chem. 277, 12208–12214 (2002).
  Article CAS PubMed Google Scholar
• Scheufler, C. et al. Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70–Hsp90 multichaperone machine. Cell 101, 199–210 (2000). Structural elucidation of how multichaperone complexes can be formed by adapter proteins.
  Article CAS PubMed Google Scholar
• Prodromou, C. et al. Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones. Embo J. 18, 754–762 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, Y. S., Marcu, M. G. & Neckers, L. Quantum chemical calculations and mutational analysis suggest heat shock protein 90 catalyzes trans-cis isomerization of geldanamycin. Chem. Biol. 11, 991–998 (2004).
  Article CAS PubMed Google Scholar
• Roe, S. M. et al. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J. Med. Chem. 42, 260–266 (1999).
  Article CAS PubMed Google Scholar
• Xu, W. et al. Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu. Proc. Natl Acad. Sci. USA 99, 12847–12852 (2002). Identification of a mechanism by which chaperone interactions regulate the cellular level of a receptor-linked tyrosine kinase.
  Article CAS PubMed PubMed Central Google Scholar
• Nathan, D. F. & Lindquist, S. Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase. Mol. Cell. Biol. 15, 3917–3925 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Birnby, D. A. et al. A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21) regulate a common set of chemosensory behaviors in Caenorhabditis elegans. Genetics 155, 85–104 (2000).
  CAS PubMed PubMed Central Google Scholar
• Yue, L. et al. Genetic analysis of viable Hsp90 alleles reveals a critical role in Drosophila spermatogenesis. Genetics 151, 1065–1079 (1999).
  CAS PubMed PubMed Central Google Scholar
• LeBlanc, R. et al. Proteasome inhibitor PS-341 inhibits human myeloma cell growth in vivo and prolongs survival in a murine model. Cancer Res. 62, 4996–5000 (2002).
  CAS PubMed Google Scholar
• Kim, J. et al. Development of a fluorescence polarization assay for the molecular chaperone Hsp90. J. Biomol. Screen. 9, 375–381 (2004).
  Article CAS PubMed Google Scholar
• Kamal, A., Boehm, M. F. & Burrows, F. J. Therapeutic and diagnostic implications of Hsp90 activation. Trends Mol. Med. 10, 283–290 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Kamal, A. et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425, 407–410 (2003). First evidence that HSP90 in tumour cells is found in multimolecular complexes with higher affinity for 17AAG than the largely uncomplexed HSP90 found in normal cells. This paper provides a biochemical explanation for why a useful therapeutic index might exist for HSP90 inhibitors.
  Article CAS PubMed Google Scholar
• Workman, P. Altered states: selectively drugging the Hsp90 cancer chaperone. Trends Mol. Med. 10, 47–51 (2004).
  Article CAS PubMed Google Scholar
• Yun, B. G., Huang, W., Leach, N., Hartson, S. D. & Matts, R. L. Novobiocin induces a distinct conformation of Hsp90 and alters Hsp90-cochaperone-client interactions. Biochemistry 43, 8217–8229 (2004).
  Article CAS PubMed Google Scholar
• Marcu, M. G., Schulte, T. W. & Neckers, L. Novobiocin and related coumarins and depletion of heat shock protein 90-dependent signaling proteins. J. Natl Cancer Inst. 92, 242–248 (2000).
  Article CAS PubMed Google Scholar
• Marcu, M. G., Chadli, A., Bouhouche, I., Catelli, M. & Neckers, L. M. The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the C-terminus of the chaperone. J. Biol. Chem. 275, 37181–37186 (2000). Biochemical evidence for a second, cryptic ATP-binding site in HSP90 that binds the antibiotic novobiocin, albeit with very low affinity.
  Article CAS PubMed Google Scholar
• Itoh, H. et al. A novel chaperone-activity-reducing mechanism of the 90-kDa molecular chaperone HSP90. Biochem. J. 343, 697–703 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Rosenhagen, M. C. et al. The heat shock protein 90-targeting drug cisplatin selectively inhibits steroid receptor activation. Mol. Endocrinol. 17, 1991–2001 (2003).
  Article CAS PubMed Google Scholar
• McIlwrath, A. J., Brunton, V. G. & Brown, R. Cell-cycle arrest and p53 accumulation induced by geldanamycin in human ovarian tumour cells. Cancer Chemother. Pharmacol. 37, 423–428 (1996).
  Article CAS PubMed Google Scholar
• Nomura, M. et al. Geldanamycin induces mitotic catastrophe and subsequent apoptosis in human glioma cells. J. Cell. Physiol. 201, 374–384 (2004).
  Article CAS PubMed Google Scholar
• Srethapakdi, M., Liu, F., Tavorath, R. & Rosen, N. Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product-dependent G1 arrest. Cancer Res. 60, 3940–3946 (2000).
  CAS PubMed Google Scholar
• Hostein, I., Robertson, D., DiStefano, F., Workman, P. & Clarke, P. A. Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis. Cancer Res. 61, 4003–4009 (2001).
  CAS PubMed Google Scholar
• Bagatell, R., Beliakoff, J., David, C. L., Marron, M. T. & Whitesell, L. Hsp90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin. Int. J. Cancer 113, 179–188 (2005).
  Article CAS PubMed Google Scholar
• Munster, P. N., Basso, A., Solit, D., Norton, L. & Rosen, N. Modulation of Hsp90 function by ansamycins sensitizes breast cancer cells to chemotherapy-induced apoptosis in an RB- and schedule-dependent manner. See: E. A. Sausville, Combining cytotoxics and 17-allylamino, 17-demethoxygeldanamycin: sequence and tumor biology matters, Clin. Cancer Res. 7, 2155–2158 (2001). Clin. Cancer Res. 7, 2228–2236 (2001). Evidence for the ability of HSP90 inhibitors to increase the anticancer activity of cytotoxic chemotherapeutic agents.
  Google Scholar
• Basso, A. D., Solit, D. B., Munster, P. N. & Rosen, N. Ansamycin antibiotics inhibit Akt activation and cyclin D expression in breast cancer cells that overexpress HER2. Oncogene 21, 1159–1166 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Maloney, A., Clarke, P. A. & Workman, P. Genes and proteins governing the cellular sensitivity to HSP90 inhibitors: a mechanistic perspective. Curr. Cancer Drug Targets 3, 331–341 (2003).
  Article CAS PubMed Google Scholar
• Gorre, M. E., Ellwood-Yen, K., Chiosis, G., Rosen, N. & Sawyers, C. L. BCR–ABL point mutants isolated from patients with imatinib mesylate-resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR–ABL chaperone heat shock protein 90. Blood 100, 3041–3044 (2002). Clinical BCR–ABL mutations that render the kinase resistant to the active site inhibitor imatinib (Glivec) remain HSP90-dependent and, as a result, quite sensitive to geldanamycin-stimulated degradation. Such a lack of cross-resistance provides the rationale for current clinical studies of 17AAG in imatinib-resistant patients.
  Article CAS PubMed Google Scholar
• Bonvini, P., Dalla Rosa, H., Vignes, N. & Rosolen, A. Ubiquitination and proteasomal degradation of nucleophosmin-anaplastic lymphoma kinase induced by 17-allylamino-demethoxygeldanamycin: role of the co-chaperone carboxyl heat shock protein 70-interacting protein. Cancer Res. 64, 3256–3264 (2004).
  Article CAS PubMed Google Scholar
• Beliakoff, J. et al. Hormone-refractory breast cancer remains sensitive to the antitumor activity of heat shock protein 90 inhibitors. Clin. Cancer Res. 9, 4961–4971 (2003).
  CAS PubMed Google Scholar
• Solit, D. B. et al. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/NEU and inhibits the growth of prostate cancer xenografts. Clin. Cancer Res. 8, 986–993 (2002).
  CAS PubMed Google Scholar
• Munster, P. N., Marchion, D. C., Basso, A. D. & Rosen, N. Degradation of HER2 by ansamycins induces growth arrest and apoptosis in cells with HER2 overexpression via a HER3, phosphatidylinositol 3'-kinase-AKT-dependent pathway. Cancer Res. 62, 3132–3137 (2002).
  CAS PubMed Google Scholar
• Solit, D. B., Basso, A. D., Olshen, A. B., Scher, H. I. & Rosen, N. Inhibition of heat shock protein 90 function down-regulates akt kinase and sensitizes tumors to taxol. Cancer Res. 63, 2139–2144 (2003).
  CAS PubMed Google Scholar
• Bagatell, R. et al. Induction of a heat shock factor 1-dependent stress response alters the cytotoxic activity of Hsp90 binding agents. Clin. Cancer Res. 6, 3312–3318 (2000).
  CAS PubMed Google Scholar
• Clarke, P. A. et al. Gene expression profiling of human colon cancer cells following inhibition of signal transduction by 17-allylamino-17-demethoxygeldanamycin, an inhibitor of the hsp90 molecular chaperone. Oncogene. 19, 4125–4133 (2000).
  Article CAS PubMed Google Scholar
• Burger, A. M., Fiebig, H. H., Stinson, S. F. & Sausville, E. A. 17-(Allylamino)-17-demethoxygeldanamycin activity in human melanoma models. Anticancer Drugs 15, 377–387 (2004).
  Article CAS PubMed Google Scholar
• Lu, A., Ran, R., Parmentier-Batteur, S., Nee, A. & Sharp, F. R. Geldanamycin induces heat shock proteins in brain and protects against focal cerebral ischemia. J. Neurochem. 81, 355–364 (2002).
  Article CAS PubMed Google Scholar
• Sittler, A. et al. Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease. Hum. Mol. Genet. 10, 1307–1315 (2001).
  Article CAS PubMed Google Scholar
• Auluck, P. K., Meulener, M. C. & Bonini, N. M. Mechanisms of suppression of α-synuclein neurotoxicity by geldanamycin in Drosophila. J. Biol. Chem. 280, 2873–2878 (2005).
  Article CAS PubMed Google Scholar
• Egorin, M. J. et al. Plasma pharmacokinetics and tissue distribution of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) in CD2F1 mice1. Cancer Chemother. Pharmacol. 47, 291–302 (2001).
  Article CAS PubMed Google Scholar
• Kelland, L. R., Sharp, S. Y., Rogers, P. M., Myers, T. G. & Workman, P. DT-Diaphorase expression and tumor cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat shock protein 90. J. Natl Cancer Inst. 91, 1940–1949 (1999).
  Article CAS PubMed Google Scholar
• Goetz, M. P. et al. Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer. J. Clin. Oncol. 23, 1078–1087 (2005).
  Article CAS PubMed Google Scholar
• Rajkumar, S. V., Richardson, P. G., Hideshima, T. & Anderson, K. C. Proteasome inhibition as a novel therapeutic target in human cancer. J. Clin. Oncol. 23, 630–639 (2005).
  Article CAS PubMed Google Scholar
• Grem, J. L. et al. Phase I and pharmacologic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with solid tumors. J. Clin. Oncol. 23, 1885–1893 (2005).
  Article CAS PubMed Google Scholar
• Banerji, U. et al. Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies. J. Clin. Oncol. 23, 4152–4161 (2005). Report of a phase I trial of 17AAG demonstrating the modulation of HSP90 function by systemically tolerable drug exposures and the stabilization of disease in two melanoma patients.
  Article CAS PubMed Google Scholar
• Enmon, R. et al. Combination treatment with 17-N-allylamino-17-demethoxy geldanamycin and acute irradiation produces supra-additive growth suppression in human prostate carcinoma spheroids. Cancer Res. 63, 8393–8399 (2003).
  CAS PubMed Google Scholar
• Bisht, K. S. et al. Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity. Cancer Res. 63, 8984–8995 (2003).
  CAS PubMed Google Scholar
• McCollum, A., Toft, D. O. & Erlichman, C. Geldanamycin enhances cisplatin cytotoxicity through loss of Akt activation in A549 cells. Clin. Cancer Res. 9 (Suppl.), 6178 (2003).
  Google Scholar
• Vasilevskaya, I. A., Rakitina, T. V. & O'Dwyer, P. J. Geldanamycin and its 17-allylamino-17-demethoxy analogue antagonize the action of cisplatin in human colon adenocarcinoma cells: differential caspase activation as a basis for interaction. Cancer Res. 63, 3241–3246 (2003).
  CAS PubMed Google Scholar
• Mimnaugh, E. G. et al. Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity. Mol. Cancer Ther. 3, 551–566 (2004).
  Article CAS PubMed Google Scholar
• Mitsiades, C. S., Mitsiades, N., Richardson, P. G., Treon, S. P. & Anderson, K. C. Novel biologically based therapies for Waldenstrom's macroglobulinemia. Semin. Oncol. 30, 309–312 (2003).
  Article CAS PubMed Google Scholar
• Rahmani, M. et al. Coadministration of the heat shock protein 90 antagonist 17-allylamino- 17-demethoxygeldanamycin with suberoylanilide hydroxamic acid or sodium butyrate synergistically induces apoptosis in human leukemia cells. Cancer Res. 63, 8420–8427 (2003).
  CAS PubMed Google Scholar
• Yu, X. et al. Modulation of p53, ErbB1, ErbB2, and Raf-1 expression in lung cancer cells by depsipeptide FR901228. J. Natl Cancer Inst. 94, 504–513 (2002).
  Article CAS PubMed Google Scholar
• Dymock, B. et al. Adenine derived inhibitors of the molecular chaperone HSP90–SAR explained through multiple X-ray structures. Bioorg. Med. Chem. Lett. 14, 325–328 (2004).
  Article CAS PubMed Google Scholar
• Chiosis, G., Lucas, B., Shtil, A., Huezo, H. & Rosen, N. Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase. Bioorg. Med. Chem. 10, 3555–3564 (2002).
  Article CAS PubMed Google Scholar
• Rowlands, M. G. et al. High-throughput screening assay for inhibitors of heat-shock protein 90 ATPase activity. Anal. Biochem. 327, 176–183 (2004).
  Article CAS PubMed Google Scholar
• Turbyville, T. J., Wijeratne, E. M. K., Whitesell, L. & Gunatilaka, A. A. L. The anticancer activity of the fungal metabolite terrecyclic acid A is associated with modulation of multiple cellular stress response pathways. Mol. Cancer Ther. (in the press).
• Barbosa, J. A. et al. Discovery of novel small molecule Hsp90 complex inhibitors using a forward chemical genetics approach. Clin. Cancer Res. 9 (Suppl.), 6176 (2003).
  Google Scholar
• Kuduk, S. D. et al. Synthesis and evaluation of geldanamycin-testosterone hybrids. Bioorg. Med. Chem. Lett. 10, 1303–1306 (2000).
  Article CAS PubMed Google Scholar
• Zheng, F. F. et al. Identification of a geldanamycin dimer that induces the selective degradation of HER-family tyrosine kinases. Cancer Res. 60, 2090–2094 (2000).
  CAS PubMed Google Scholar
• Patel, K. et al. Engineered biosynthesis of geldanamycin analogs for Hsp90 inhibition. Chem. Biol. 11, 1625–1633 (2004).
  Article CAS PubMed Google Scholar
• Soga, S. et al. KF25706, a novel oxime derivative of radicicol, exhibits in vivo antitumor activity via selective depletion of Hsp90 binding signaling molecules. Cancer Res. 59, 2931–2938 (1999).
  CAS PubMed Google Scholar
• Eiseman, J. L. et al. Pharmacokinetics and pharmacodynamics of 17-demethoxy 17-[[(2-dimethylamino)ethyl]amino]geldanamycin (17DMAG, NSC 707545) in C. B-17 SCID mice bearing MDA-MB-231 human breast cancer xenografts. Cancer Chemother. Pharmacol. 55, 21–32 (2005).
  Article CAS PubMed Google Scholar
• Schulte, T. W. et al. Destabilization of Raf-1 by geldanamycin leads to disruption of the RAF-1-MEK-mitogen-activated protein kinase signalling pathway. Mol. Cell. Biol. 16, 5839–5845 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Stepanova, L., Leng, X., Parker, S. B. & Harper, J. W. Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Devel. 10, 1491–1502 (1996).
  Article CAS PubMed Google Scholar
• Holt, S. E. et al. Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Devel. 13, 817–824 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Isaacs, J. S. et al. Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 α-degradative pathway. J. Biol. Chem. 277, 29936–29944 (2002).
  Article CAS PubMed Google Scholar
• Falsone, F. M., Leptihn, S., Osterauer, A., Haslbeck, M. & Buchner, J. Oncogenic mutations reduce the stability of Src kinase. J. Mol. Biol. 344, 281–291 (2004).
  Article PubMed CAS Google Scholar