Cancer Letters
Volume 206, Issue 2 , Pages 149-157 , 8 April 2004

Combinatorial attack on multistep oncogenesis by inhibiting the Hsp90 molecular chaperone

  • Paul Workman

      Affiliations

    • Corresponding Author InformationTel.: +44-208-722-4301; fax: +44-208-722-4324

Received 24 July 2003 ,Accepted 13 August 2003.

References 

  1. In:  Lund DP editors. Molecular Chaperones in the Cell. Oxford: Oxford University Press; 2001;
  2. Sangster TA, Queitsch C, Lindquist S. Hsp90 and chromatin. Where is the link?. Cell Cycle. 2003;23:166–168
  3. Rutherford SL, Lindquist S. Hsp90 as a capacitor for morphological evolution. Nature. 1998;396:336–342
  4. Jolly C, Morimoto RI. Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J. Natl. Cancer Inst. 2000;92:1564–1572
  5. Scheibel T, Buchner J. The Hsp90 complex-A super-chaperone machine as a novel drug target. Biochem. Pharmacol. 1998;56:675–682
  6. Smith DF, Whitesell L, Katsanis E. Molecular chaperones: biology and prospects for pharmacological intervention. Pharmacol. Rev. 1998;50:493–513
  7. Neckers L, Schulte TW, Mimnaugh E. Geldanmycin as a potential anticancer agent: its molecular target and biochemical activity. Invest. New Drugs. 1999;17:361–373
  8. Maloney A, Workman P. Hsp90 as a new therapeutic target for cancer therapy: the story unfolds. Exp. Opin. Biol. Ther. 2002;2:3–24
  9. Workman P. Pharmacogenomics in cancer drug discovery and development: inhibitors of the Hsp90 molecular chaperone. Cancer Detect. Prevent. 2002;26:405–410
  10. Isaacs JS, Xu W, Neckers L. Heat shock protein 90 as a molecular target for cancer therapeutics. Cancer Cell. 2003;3:213–217
  11. Banerji U, Clarke P, Walton M, O'Donnell A, Raynaud F, Turner A, et al.  Preclinical and clinical activity of the molecular chaperone inhibitor 17-allylamino, 17-demethoxygeldanamycin (17AAG) in malignant melanoma. Proc. Am. Assoc. Cancer Res. 2003;677–678
  12. Buchner J. Hsp90 and Co.—a holding for folding. Trends Biochem. Sci. 1999;24:136–141
  13. De Carcer G, Avides MC, Lallena MJ, Glover DM, Gonzalez C. Requirement of Hsp90 for centrosomal function reflects its regulation of Polo kinase stability. Eur. Mol. Biol. Org. J. 2001;20:2878–2884
  14. Goes FS, Martin J. Hsp90 chaperone complexes are required for the activity and stability of yeast protein kinases Mik1, Wee1amd Swe1. Eur. J. Biochem. 2001;268:2281–2289
  15. Queitsch C, Sangster TA, Lindquist S. Hsp90 as a capacitor of phenotypic variation. Nature. 2002;417:618–624
  16. Lindquist SL, Henikoff S. Self-perpetuating structural states in biology, disease and genetics. Proc. Natl. Acad. Sci. USA. 2002;99(Suppl. 4):16377
  17. Sollars V, Lu X, Xiao L, Wang X, Garfinkel MD, Ruden DM. Evidence for an epigenetic mechanism by which Hsp90 acts as a capacitor for morphological evolution. Nat. Genet. 2003;33:70–74
  18. Prodromou C, Pearl LH. Structure and in vivo function of Hsp90. Curr. Opin. Struct. Biol. 2000;10:46–51
  19. Meyer P, Prodromou C, Hu B, Vaughan C, Panaretou B, Piper WP, et al. Structural and functional analysis of the middle segment of Hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions. Mol. Cell. 2003;11:647–658
  20. Prodromou C, Roe SM, O'Brien R, Ladbury JE, Pier PW, Pearl LH. Identification and structural characterisation of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell. 1997;90:65–70
  21. Stebbings CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP. Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumour agent. Cell. 1997;89:239–250
  22. Dutta R, Inouye M. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem. Sci. 2000;25:24–28
  23. Panaretou B, Siligardi G, Meyer P, Maloney A, Sullivan JK, Singh S, et al.  Activation of the ATPase activity of Hsp90 by the stress-regulated co-chaperone Aha1. Mol. Cell. 2002;10:1307–1318
  24. Ferrarini M, Helta S, Zocchi MR, Rugarli C. Unusual expression and localisation of heat shock proteins in human tumour cells. Int. J. Cancer. 1992;16:613–619
  25. Weinstein IB. Addiction to oncogenes. Science. 2002;297:63–64
  26. Workman P. Cancer genome targets—RAF-ing up tumour cells to overcome oncogene addiction. Exp. Rev. Anticancer Ther. 2002;2:611–614
  27. Evan G, Vousden KH. Proliferation, cell cycle and apoptosis in cancer research. Nature. 2001;411:342–348
  28. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70
  29. Prodromou C, Roe SM, Piper PW, Pearl LH. A molecular clamp in the crystal structure of the N-terminal domain of the yeast Hsp90 chaperone. Nat. Struct. Biol. 1997;4:477–482
  30. Panaretou B, Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW, et al. ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo. Eur. Mol. Biol. Org. J. 1998;17:4829–4836
  31. Roe SM, Prodromou C, Brien RO, Ladbury JE, Piper PW, Pearl LH. The structural basis for inhibition of the Hsp90 molecular chaperone, by the anti-tumour antibiotics radicicol and geldanamycin. J. Med. Chem. 1999;42:260–266
  32. Connell P, Ballinger CA, Jiang JH, Wu YX, Thompson LJ, Hohfeld J, et al. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat. Cell Biol. 2001;3:93–96
  33. Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, et al. Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Mol. Cell. Biol. 1999;19:4535–4545
  34. Soga S, Neckers LM, Schulte TW, Shiotsu Y, Akasaka K, Narumi H, et al.  KF25706, a novel oxime derivative of radicicol, exhibits in vivo antitumor activity via selective depletion of Hsp90 binding signaling molecules. Cancer Res. 1999;59:2931–2938
  35. Supko JG, Hickman RL, Greever MR. L. Malspies, Preclinical pharmacologic evaluation of geldanamycin as an antitumour agent. Cancer Chemother. Pharmacol. 1995;36:305–310
  36. Kelland LR, Sharp SY, Rogers PM, Myers TG, Workman P. DT-diaphorase expression and tumour cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat shock protein 90. J. Natl. Cancer Inst. 1999;91:1940–1949
  37. Sausville EA, Tomaszewski JE, Ivy P. Clinical development of 17-allylamino, 17-demethoxygeldanamycin. Curr. Cancer Drug Targets. 2003;3:377–383
  38. Banerji U, O'Donnell A, Scurr M, Benson C, Brock C, Hanwell J, et al.  A pharmacokinetically (Pk)–pharmcodynamically (Pd) driven phase 1 trial of the Hsp90 molecular chaperone inhibitor 17-allylamino, 17-demethoxygeldanamycin (17AAG). Proc. Am. Assoc. Cancer Res. 2002;43:272; [Abstract 1352]
  39. Chiosis G, Huezo H, Rosen N, Mimnaugh E, Whitesell L, Neckers L. 17AAG: low target binding affinity and potent cell activity—finding an explanation. Mol. Cancer Ther. 2003;2:123–129
  40. Workman P. Auditing the pharmacological accounts for Hsp90 molecular chaperone inhibitors: unfolding the relationship between pharmacokinetics and pharmacodynamics. Mol. Cancer Ther. 2003;2:131–138
  41. Smith V, Sausville E, Camalier R, Fiebig HH, Burger AM. 17-DMAG (NSC 70745), a water soluble geldanamycin analog, has superior in vitro and in vivo antitumour activity compared to the hsp90 inhibitor 17AAG. Eur. J. Cancer. 2002;38:S60
  42. Soga S, Sharma SV, Shiotsu Y. Stereospecific antitumour activity of radicicol oxime derivatives. Cancer Chemother. Pharmacol. 2001;48:435–445
  43. Marcu MG, Schulte TW, Neckers L. Novobiocin and related coumarins and depletion of heat shock protein 90-dependent signalling proteins. J. Natl. Cancer Inst. 2000;92:242–248
  44. Marcu MG, Chadli A, Bouhouche I, Catelli M, Neckers L. The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J. Biol. Chem. 2000;275:37181–37186
  45. Itoh H, Ogura M, Komatsuda A, Wakui H, Miura AB, Tashima Y. A novel chaperone-activity-reducing mechanism of the 90-kDa molecular chaperone HSP90. Biochem. J. 1999;343:697–703
  46. Chiosis G, Timaul MN, Lucas B, Munster PN, Zheng FF, Sepp-Lorenzino L, et al. A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells. Chem. Biol. 2001;8:289–299
  47. 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. 2002;10:3555–3564
  48. Aherne W, Maloney A, Sharp S, Clarke P, Walton M, Hardcastle A, et al.  Discovery of a novel synthetic inhibitor of the Hsp90 molecular chaperone. Proc. Am. Assoc. Cancer Res. 2003;44:799
  49. Workman P. Scoring a bull's-eye against cancer genome targets. Curr. Opin. Pharmacol. 2001;1:342–352
  50. Kamal A, Thao L, Sensitaffar J, Zhang L, Boehm MF, Fritz LC, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature. 2003;425:407–410
  51. Clarke PA, Hostein I, Banerji U, Di Stefano F, Maloney A, Walton M, et al.  Gene expression profiling of human colon cancer cells following inhibition of signal transduction by 17-allylamino-17-demethoxygeldanamycin, an inhibitor of thee hsp90 molecular chaperone. Oncogene. 2000;19:4125–4133

PII: S0304-3835(03)00634-7

doi: 10.1016/j.canlet.2003.08.032

Cancer Letters
Volume 206, Issue 2 , Pages 149-157 , 8 April 2004

Article Tools

* Image Usage & Resolution