Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Targeting Heat Shock Proteins in Colorectal Cancer

  • Chapter
Heat Shock Protein-Based Therapies

Part of the book series: Heat Shock Proteins ((HESP,volume 9))

Abstract

Colorectal cancer (CRC) causes over half a million deaths worldwide and has a particularly poor prognosis when diagnosed at an advanced stage. Heat shock proteins (HSP) have been found to be elevated in CRC patients and HSPB1, HSPA1A and HSPC1 has been shown to have some prognostic value. CRC, in common with all cancers, has important associated oncogene and tumor suppressor gene associations and we show how many of these interact directly with one or more of the HSP. We discuss the current chemotherapeutic options available to the clinician when presented with CRC and how these may be improved with a consideration of the role of HSP in the development of the tumor as well as the response to therapy. Direct manipulation of HSP has the potential to decrease the therapeutic dose of anti-tumor drugs and we propose novel strategies that have the potential to be adapted to the clinic.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AJCC:

American Joint Committee on Cancer

APC:

Antigen presenting cells

CRC:

Colorectal cancer

CT:

Computed tomography

FAP:

Familial adenomatous polyposis

HNPCC:

Non-polyposis colorectal cancer

HSP:

Heat Shock Proteins

TNM:

Tumour node metastasis

UICC:

Union for International Cancer Control

References

  1. International Agency for Research on Cancer (IARC) (2008) Colorectal cancer incidence, mortality and prevalence worldwide in 2008. IARC, France

    Google Scholar 

  2. Cancer Research UK (2013) Bowel cancer. Cancer Statistics Key Facts. Cancer Research UK, London

    Google Scholar 

  3. Lynch HT, de la Chapelle A (1999) Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 36:801–818

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348:919–932

    CAS  PubMed  Google Scholar 

  5. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    CAS  PubMed  Google Scholar 

  6. Cunningham D, Atkin W, Lenz H-J, Lynch HT, Minsky B, Nordlinger B, Starling N (2010) Colorectal cancer. Lancet 375:1030–1047

    PubMed  Google Scholar 

  7. Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP, Jarvinen H, Powell SM, Jen J, Hamilton SR et al (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260:812–816

    CAS  PubMed  Google Scholar 

  8. Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M (1993) Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363:558–561

    CAS  PubMed  Google Scholar 

  9. Cunningham JM, Christensen ER, Tester DJ, Kim CY, Roche PC, Burgart LJ, Thibodeau SN (1998) Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 58:3455–3460

    CAS  PubMed  Google Scholar 

  10. Tadros M, Anderson JC (2013) Serrated polyps: clinical implications and future directions. Curr Gastroenterol Rep 15:342

    PubMed  Google Scholar 

  11. Noffsinger AE (2009) Serrated polyps and colorectal cancer: new pathway to malignancy. Annu Rev Pathol 4:343–364

    CAS  PubMed  Google Scholar 

  12. Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang ZM, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JKV, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PVK, Ballinger DG, Sparks AB, Hartigan J, Smith DR, Suh E, Papadopoulos N, Buckhaults P, Markowitz SD, Parmigiani G, Kinzler KW, Velculescu VE, Vogelstein B (2007) The genomic landscapes of human breast and colorectal cancers. Science 318:1108–1113

    CAS  PubMed  Google Scholar 

  13. Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789–799

    CAS  PubMed  Google Scholar 

  14. Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR (2004) A census of human cancer genes. Nat Rev Cancer 4:177–183

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Saidi HS, Karuri D, Nyaim EO (2008) Correlation of clinical data, anatomical site and disease stage in colorectal cancer. East Afr Med J 85:259–262

    CAS  PubMed  Google Scholar 

  16. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30

    PubMed  Google Scholar 

  17. Holme O, Bretthauer M, Fretheim A, Odgaard-Jensen J, Hoff G (2013) Flexible sigmoidoscopy versus faecal occult blood testing for colorectal cancer screening in asymptomatic individuals. Cochrane Database Syst Rev 9:Cd009259

    PubMed  Google Scholar 

  18. Hewitson P, Glasziou P, Watson E, Towler B, Irwig L (2008) Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (hemoccult): an update. Am J Gastroenterol 103:1541–1549

    PubMed  Google Scholar 

  19. Rees CJ, Bevan R (2013) The National Health Service Bowel Cancer Screening Program: the early years. Expert Rev Gastroenterol Hepatol 7:421–437

    CAS  PubMed  Google Scholar 

  20. Engstrom PF, Arnoletti JP, Benson AB, Chen YJ, Choti MA, Cooper HS, Covey A, Dilawari RA, Early DS, Enzinger PC, Fakih MG, Fleshman J, Fuchs C, Grem JL, Kiel K, Knol JA, Leong LA, Lin E, Mulcahy MF, Rao S, Ryan DP, Saltz L, Shibata D, Skibber JM, Sofocleous C, Thomas J, Venook AP, Willett C (2009) Colon cancer. J Natl Compr Canc Netw 7:778–831

    PubMed  Google Scholar 

  21. Engstrom PF, Arnoletti JP, Benson AB, Chen YJ, Choti MA, Cooper HS, Covey A, Dilawari RA, Early DS, Enzinger PC, Fakih MG, Fleshman J, Fuchs C, Grem JL, Kiel K, Knol JA, Leong LA, Lin E, Mulcahy MF, Rao S, Ryan DP, Saltz L, Shibata D, Skibber JM, Sofocleous C, Thomas J, Venook AP, Willett C (2009) Rectal cancer. J Natl Compr Canc Netw 7:838–881

    PubMed  Google Scholar 

  22. Taylor FG, Quirke P, Heald RJ, Moran B, Blomqvist L, Swift I, Sebag-Montefiore DJ, Tekkis P, Brown G (2011) Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study that recruited consecutive patients with rectal cancer. Ann Surg 253:711–719

    PubMed  Google Scholar 

  23. American Joint Committee on Cancer (2010) Colon and rectum. In: Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds) AJCC cancer staging manual seventh edition. Springer-Verlag, New York

    Google Scholar 

  24. Ueno H, Shirouzu K, Eishi Y, Yamada K, Kusumi T, Kushima R, Ikegami M, Murata A, Okuno K, Sato T, Ajioka Y, Ochiai A, Shimazaki H, Nakamura T, Kawachi H, Kojima M, Akagi Y, Sugihara K (2013) Characterization of perineural invasion as a component of colorectal cancer staging. Am J Surg Pathol 37:1542–1549

    PubMed  Google Scholar 

  25. Morikawa T, Kuchiba A, Qian Z, Mino-Kenudson M, Hornick J, Yamauchi M, Imamura Y, Liao X, Nishihara R, Meyerhardt J, Fuchs C, Ogino S (2012) Prognostic significance and molecular associations of tumor growth pattern in colorectal cancer. Ann Surg Oncol 19:1944–1953

    PubMed Central  PubMed  Google Scholar 

  26. Betge J, Pollheimer MJ, Lindtner RA, Kornprat P, Schlemmer A, Rehak P, Vieth M, Hoefler G, Langner C (2012) Intramural and extramural vascular invasion in colorectal cancer: prognostic significance and quality of pathology reporting. Cancer 118:628–638

    PubMed  Google Scholar 

  27. Newton KF, Newman W, Hill J (2012) Review of biomarkers in colorectal cancer. Colorectal Dis 14:3–17

    CAS  PubMed  Google Scholar 

  28. Ezzeldin HH, Lee AM, Mattison LK, Diasio RB (2005) Methylation of the DPYD promoter: an alternative mechanism for dihydropyrimidine dehydrogenase deficiency in cancer patients. Clin Cancer Res 11:8699–8705

    CAS  PubMed  Google Scholar 

  29. Raida M, Schwabe W, Hausler P, Van Kuilenburg AB, Van Gennip AH, Behnke D, Hoffken K (2001) Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5′-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)- related toxicity compared with controls. Clin Cancer Res 7:2832–2839

    CAS  PubMed  Google Scholar 

  30. Biason P, Masier S, Toffoli G (2008) UGT1A1*28 and other UGT1A polymorphisms as determinants of irinotecan toxicity. J Chemother 20:158–165

    CAS  PubMed  Google Scholar 

  31. Siena S, Sartore-Bianchi A, Di Nicolantonio F, Balfour J, Bardelli A (2009) Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 101:1308–1324

    CAS  PubMed Central  PubMed  Google Scholar 

  32. National Cancer Intelligence Network (NCIN) (2009) Colorectal survival by stage. NCIN, London

    Google Scholar 

  33. Foxtrot Collaborative G (2012) Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol 13:1152–1160

    Google Scholar 

  34. Palmer G, Martling A, Cedermark B, Holm T (2007) A population-based study on the management and outcome in patients with locally recurrent rectal cancer. Ann Surg Oncol 14:447–454

    CAS  PubMed  Google Scholar 

  35. Rodel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sulberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Kohler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R (2012) Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol 13:679–687

    PubMed  Google Scholar 

  36. Goffin JR, Zbuk K (2013) Epidermal growth factor receptor: pathway, therapies, and pipeline. Clin Ther 35:1282–1303

    CAS  PubMed  Google Scholar 

  37. Kelsey I, Manning BD (2013) mTORC1 status dictates tumor response to targeted therapeutics. Sci Signal 6:pe31

    PubMed  Google Scholar 

  38. Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee MK, Attar N, Sazegar H, Chodon T, Nelson SF, McArthur G, Sosman JA, Ribas A, Lo RS (2010) Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468:973–977

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Calderwood SK, Ciocca DR (2008) Heat shock proteins: stress proteins with Janus-like properties in cancer. Int J Hyperthermia 24:31–39

    CAS  PubMed  Google Scholar 

  40. Khalil AA, Kabapy NF, Deraz SF, Smith C (2011) Heat shock proteins in oncology: diagnostic biomarkers or therapeutic targets? Biochim Biophys Acta 1816:89–104

    CAS  PubMed  Google Scholar 

  41. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    CAS  PubMed  Google Scholar 

  42. Li D, Marchenko ND, Schulz R, Fischer V, Velasco-Hernandez T, Talos F, Moll UM (2011) Functional inactivation of endogenous MDM2 and CHIP by HSP90 causes aberrant stabilization of mutant p53 in human cancer cells. Mol Cancer Res 9:577–588

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Wiech M, Olszewski MB, Tracz-Gaszewska Z, Wawrzynow B, Zylicz M, Zylicz A (2012) Molecular mechanism of mutant p53 stabilization: the role of HSP70 and MDM2. PLoS One 7:e51426

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Priya S, Sharma SK, Goloubinoff P (2013) Molecular chaperones as enzymes that catalytically unfold misfolded polypeptides. FEBS Lett 587:1981–1987

    CAS  PubMed  Google Scholar 

  45. Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G (2006) Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties. Cell Cycle 5:2592–2601

    CAS  PubMed  Google Scholar 

  46. Eustace BK, Sakurai T, Stewart JK, Yimlamai D, Unger C, Zehetmeier C, Lain B, Torella C, Henning SW, Beste G, Scroggins BT, Neckers L, Ilag LL, Jay DG (2004) Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness. Nat Cell Biol 6:507–514

    CAS  PubMed  Google Scholar 

  47. Tsutsumi S, Scroggins B, Koga F, Lee MJ, Trepel J, Felts S, Carreras C, Neckers L (2008) A small molecule cell-impermeant Hsp90 antagonist inhibits tumor cell motility and invasion. Oncogene 27:2478–2487

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Gastpar R, Gross C, Rossbacher L, Ellwart J, Riegger J, Multhoff G (2004) The cell surface-localized heat shock protein 70 epitope TKD induces migration and cytolytic activity selectively in human NK cells. J Immunol 172:972–980

    CAS  PubMed  Google Scholar 

  49. Multhoff G, Botzler C, Jennen L, Schmidt J, Ellwart J, Issels R (1997) Heat shock protein 72 on tumor cells: a recognition structure for natural killer cells. J Immunol 158:4341–4350

    CAS  PubMed  Google Scholar 

  50. Thuringer D, Jego G, Wettstein G, Terrier O, Cronier L, Yousfi N, Hebrard S, Bouchot A, Hazoume A, Joly AL, Gleave M, Rosa-Calatrava M, Solary E, Garrido C (2013) Extracellular HSP27 mediates angiogenesis through Toll-like receptor 3. Faseb J 27:4169–4183

    CAS  PubMed  Google Scholar 

  51. Murshid A, Gong J, Calderwood SK (2008) Heat-shock proteins in cancer vaccines: agents of antigen cross-presentation. Expert Rev Vaccines 7:1019–1030

    CAS  PubMed  Google Scholar 

  52. Neckers L, Workman P (2012) Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res 18:64–76

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC, Burrows FJ (2003) A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425:407–410

    CAS  PubMed  Google Scholar 

  54. Xu L, Eiseman JL, Egorin MJ, D’Argenio DZ (2003) Physiologically-based pharmacokinetics and molecular pharmacodynamics of 17-(allylamino)-17-demethoxygeldanamycin and its active metabolite in tumor-bearing mice. J Pharmacokinet Pharmacodyn 30:185–219

    CAS  PubMed  Google Scholar 

  55. Gooljarsingh LT, Fernandes C, Yan K, Zhang H, Grooms M, Johanson K, Sinnamon RH, Kirkpatrick RB, Kerrigan J, Lewis T, Arnone M, King AJ, Lai Z, Copeland RA, Tummino PJ (2006) A biochemical rationale for the anticancer effects of Hsp90 inhibitors: slow, tight binding inhibition by geldanamycin and its analogues. Proc Natl Acad Sci U S A 103:7625–7630

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Burnett JC, Rossi JJ (2012) RNA-based therapeutics: current progress and future prospects. Chem Biol 19:60–71

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Kassem H, Sangar V, Cowan R, Clarke N, Margison GP (2002) A potential role of heat shock proteins and nicotinamide N-methyl transferase in predicting response to radiation in bladder cancer. Int J Cancer 101:454–460

    CAS  PubMed  Google Scholar 

  58. Mori-Iwamoto S, Kuramitsu Y, Ryozawa S, Mikuria K, Fujimoto M, Maehara S, Maehara Y, Okita K, Nakamura K, Sakaida I (2007) Proteomics finding heat shock protein 27 as a biomarker for resistance of pancreatic cancer cells to gemcitabine. Int J Oncol 31:1345–1350

    CAS  PubMed  Google Scholar 

  59. Lee SC, Sim N, Clement MV, Yadav SK, Pervaiz S (2007) Dominant negative Rac1 attenuates paclitaxel-induced apoptosis in human melanoma cells through upregulation of heat shock protein 27: a functional proteomic analysis. Proteomics 7:4112–4122

    CAS  PubMed  Google Scholar 

  60. Hadaschik BA, Jackson J, Fazli L, Zoubeidi A, Burt HM, Gleave ME, So AI (2008) Intravesically administered antisense oligonucleotides targeting heat-shock protein-27 inhibit the growth of non-muscle-invasive bladder cancer. BJU Int 102:610–616

    CAS  PubMed  Google Scholar 

  61. Zoubeidi A, Zardan A, Beraldi E, Fazli L, Sowery R, Rennie P, Nelson C, Gleave M (2007) Cooperative interactions between androgen receptor (AR) and heat-shock protein 27 facilitate AR transcriptional activity. Cancer Res 67:10455–10465

    CAS  PubMed  Google Scholar 

  62. Baylot V, Andrieu C, Katsogiannou M, Taieb D, Garcia S, Giusiano S, Acunzo J, Iovanna J, Gleave M, Garrido C, Rocchi P (2011) OGX-427 inhibits tumor progression and enhances gemcitabine chemotherapy in pancreatic cancer. Cell Death Dis 2:e221

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Matsui Y, Hadaschik BA, Fazli L, Andersen RJ, Gleave ME, So AI (2009) Intravesical combination treatment with antisense oligonucleotides targeting heat shock protein-27 and HTI-286 as a novel strategy for high-grade bladder cancer. Mol Cancer Ther 8:2402–2411

    CAS  PubMed  Google Scholar 

  64. Hadchity E, Aloy MT, Paulin C, Armandy E, Watkin E, Rousson R, Gleave M, Chapet O, Rodriguez-Lafrasse C (2009) Heat shock protein 27 as a new therapeutic target for radiation sensitization of head and neck squamous cell carcinoma. Mol Ther 17:1387–1394

    CAS  PubMed Central  PubMed  Google Scholar 

  65. OncoGenex (2013) Apatorsen (OGX-427). http://www.oncogenex.com/apatorsen-ogx-427. Accessed 4 Oct 2013

  66. Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC, Calderwood SK (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6:435–442

    CAS  PubMed  Google Scholar 

  67. Elsner L, Flugge PF, Lozano J, Muppala V, Eiz-Vesper B, Demiroglu SY, Malzahn D, Herrmann T, Brunner E, Bickeboller H, Multhoff G, Walter L, Dressel R (2010) The endogenous danger signals HSP70 and MICA cooperate in the activation of cytotoxic effector functions of NK cells. J Cell Mol Med 14:992–1002

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Wang Y, Kelly CG, Singh M, McGowan EG, Carrara AS, Bergmeier LA, Lehner T (2002) Stimulation of Th1-polarizing cytokines, C-C chemokines, maturation of dendritic cells, and adjuvant function by the peptide binding fragment of heat shock protein 70. J Immunol 169:2422–2429

    CAS  PubMed  Google Scholar 

  69. Basu S, Binder RJ, Ramalingam T, Srivastava PK (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14:303–313

    CAS  PubMed  Google Scholar 

  70. McNulty S, Colaco CA, Blandford LE, Bailey CR, Baschieri S, Todryk S (2013) Heat-shock proteins as dendritic cell-targeting vaccines – getting warmer. Immunology 139:407–415

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Liu B, DeFilippo AM, Li Z (2002) Overcoming immune tolerance to cancer by heat shock protein vaccines. Mol Cancer Ther 1:1147–1151

    CAS  PubMed  Google Scholar 

  72. Kocsis J, Mészáros T, Madaras B, Tóth É, Kamondi S, Gál P, Varga L, Prohászka Z, Füst G (2011) High levels of acute phase proteins and soluble 70 kDa heat shock proteins are independent and additive risk factors for mortality in colorectal cancer. Cell Stress Chaperones 16:49–55

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Milicevic Z, Bogojevic D, Mihailovic M, Petrovic M, Krivokapic Z (2008) Molecular characterization of hsp90 isoforms in colorectal cancer cells and its association with tumour progression. Int J Oncol 32:1169–1178

    CAS  PubMed  Google Scholar 

  74. Rozenberg P, Kocsis J, Saar M, Prohászka Z, Füst G, Fishelson Z (2013) Elevated levels of mitochondrial mortalin and cytosolic HSP70 in blood as risk factors in patients with colorectal cancer. Int J Cancer 133:514–518

    CAS  PubMed  Google Scholar 

  75. Tweedle EM, Khattak I, Ang CW, Nedjadi T, Jenkins R, Park BK, Kalirai H, Dodson A, Azadeh B, Terlizzo M, Grabsch H, Mueller W, Myint S, Clark P, Wong H, Greenhalf W, Neoptolemos JP, Rooney PS, Costello E (2010) Low molecular weight heat shock protein HSP27 is a prognostic indicator in rectal cancer but not colon cancer. Gut 59:1501–1510

    CAS  PubMed  Google Scholar 

  76. Hong DS, Banerji U, Tavana B, George GC, Aaron J, Kurzrock R (2013) Targeting the molecular chaperone heat shock protein 90 (HSP90): lessons learned and future directions. Cancer Treat Rev 39:375–387

    CAS  PubMed  Google Scholar 

  77. Krause SW, Gastpar R, Andreesen R, Gross C, Ullrich H, Thonigs G, Pfister K, Multhoff G (2004) Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase i trial. Clin Cancer Res 10:3699–3707

    CAS  PubMed  Google Scholar 

  78. Mazzaferro V, Coppa J, Carrabba MG, Rivoltini L, Schiavo M, Regalia E, Mariani L, Camerini T, Marchiano A, Andreola S, Camerini R, Corsi M, Lewis JJ, Srivastava PK, Parmiani G (2003) Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer. Clin Cancer Res 9:3235–3245

    CAS  PubMed  Google Scholar 

  79. Chen WS, Lee CC, Hsu YM, Chen CC, Huang TS (2011) Identification of heat shock protein 90alpha as an IMH-2 epitope-associated protein and correlation of its mRNA overexpression with colorectal cancer metastasis and poor prognosis. Int J Colorectal Dis 26:1009–1017

    PubMed  Google Scholar 

  80. Kocsis J, Madaras B, Toth EK, Fust G, Prohaszka Z (2010) Serum level of soluble 70-kD heat shock protein is associated with high mortality in patients with colorectal cancer without distant metastasis. Cell Stress Chaperones 15:143–151

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Kanazawa Y, Isomoto H, Oka M, Yano Y, Soda H, Shikuwa S, Takeshima F, Omagari K, Mizuta Y, Murase K, Nakagoe T, Ohtsuka K, Kohno S (2003) Expression of heat shock protein (Hsp) 70 and Hsp 40 in colorectal cancer. Med Oncol 20:157–164

    CAS  PubMed  Google Scholar 

  82. Zhang WL, Gao XQ, Han JX, Wang GQ, Yue LT (2009) Expressions of heat shock protein (HSP) family HSP 60, 70 and 90alpha in colorectal cancer tissues and their correlations to pathohistological characteristics. Ai Zheng 28:612–618

    PubMed  Google Scholar 

  83. Schmitt E, Maingret L, Puig PE, Rerole AL, Ghiringhelli F, Hammann A, Solary E, Kroemer G, Garrido C (2006) Heat shock protein 70 neutralization exerts potent antitumor effects in animal models of colon cancer and melanoma. Cancer Res 66:4191–4197

    CAS  PubMed  Google Scholar 

  84. Chen CW, Huang ZC, Liu Y, Yuan ZJ, Ning GQ, Tan LX (2009) Association between expressions of HSP70, HSP90 and efficacy of chemotherapy in colorectal cancer patients with unresectable liver metastasis. Zhonghua Wei Chang Wai Ke Za Zhi 12:346–349

    PubMed  Google Scholar 

  85. Banerjea A, Feakins RM, Nickols CD, Phillips SM, Powar MP, Bustin SA, Dorudi S (2005) Immunogenic hsp-70 is overexpressed in colorectal cancers with high-degree microsatellite instability. Dis Colon Rectum 48:2322–2328

    PubMed  Google Scholar 

  86. Suzuki K, Ito Y, Wakai K, Kawado M, Hashimoto S, Seki N, Ando M, Nishino Y, Kondo T, Watanabe Y, Ozasa K, Inoue T, Tamakoshi A (2006) Serum heat shock protein 70 levels and lung cancer risk: a case-control study nested in a large cohort study. Cancer Epidemiol Biomarkers Prev 15:1733–1737

    CAS  PubMed  Google Scholar 

  87. Abe M, Manola JB, Oh WK, Parslow DL, George DJ, Austin CL, Kantoff PW (2004) Plasma levels of heat shock protein 70 in patients with prostate cancer: a potential biomarker for prostate cancer. Clin Prostate Cancer 3:49–53

    CAS  PubMed  Google Scholar 

  88. Liu W, Ma Y, Huang L, Peng J, Zhang P, Zhang H, Chen J, Qin H (2010) Identification of HSP27 as a potential tumor marker for colorectal cancer by the two-dimensional polyacrylamide gel electrophoresis. Mol Biol Rep 37:3207–3216

    CAS  PubMed  Google Scholar 

  89. Wang F, Zhang P, Shi C, Yang Y, Qin H (2012) Immunohistochemical detection of HSP27 and hnRNP K as prognostic and predictive biomarkers for colorectal cancer. Med Oncol 29:1780–1788

    CAS  PubMed  Google Scholar 

  90. Yu Z, Zhi J, Peng X, Zhong X, Xu A (2010) Clinical significance of HSP27 expression in colorectal cancer. Mol Med Rep 3:953–958

    CAS  PubMed  Google Scholar 

  91. Chen WS, Chen CC, Chen LL, Lee CC, Huang TS (2013) Secreted heat shock protein 90alpha (HSP90alpha) induces nuclear factor-kappaB-mediated TCF12 protein expression to down-regulate E-cadherin and to enhance colorectal cancer cell migration and invasion. J Biol Chem 288:9001–9010

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Chen JS, Hsu YM, Chen CC, Chen LL, Lee CC, Huang TS (2010) Secreted heat shock protein 90alpha induces colorectal cancer cell invasion through CD91/LRP-1 and NF-kappaB-mediated integrin alphaV expression. J Biol Chem 285:25458–25466

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Cappello F, David S, Rappa F, Bucchieri F, Marasa L, Bartolotta TE, Farina F, Zummo G (2005) The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase. BMC Cancer 5:139

    PubMed Central  PubMed  Google Scholar 

  94. Hamelin C, Cornut E, Poirier F, Pons S, Beaulieu C, Charrier JP, Haidous H, Cotte E, Lambert C, Piard F, Ataman-Onal Y, Choquet-Kastylevsky G (2011) Identification and verification of heat shock protein 60 as a potential serum marker for colorectal cancer. Febs J 278:4845–4859

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Miyoshi Y, Nagase H, Ando H, Horii A, Ichii S, Nakatsuru S, Aoki T, Miki Y, Mori T, Nakamura Y (1992) Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet 1:229–233

    CAS  PubMed  Google Scholar 

  96. Powell SM, Zilz N, Beazer-Barclay Y, Bryan TM, Hamilton SR, Thibodeau SN, Vogelstein B, Kinzler KW (1992) APC mutations occur early during colorectal tumorigenesis. Nature 359:235–237

    CAS  PubMed  Google Scholar 

  97. Aoki K, Taketo MM (2007) Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci 120:3327–3335

    CAS  PubMed  Google Scholar 

  98. White BD, Chien AJ, Dawson DW (2012) Dysregulation of Wnt/beta-catenin signaling in gastrointestinal cancers. Gastroenterology 142:219–232

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Kimelman D, Xu W (2006) beta-catenin destruction complex: insights and questions from a structural perspective. Oncogene 25:7482–7491

    CAS  PubMed  Google Scholar 

  100. Fanelli MA, Montt-Guevara M, Diblasi AM, Gago FE, Tello O, Cuello-Carrion FD, Callegari E, Bausero MA, Ciocca DR (2008) P-cadherin and beta-catenin are useful prognostic markers in breast cancer patients; beta-catenin interacts with heat shock protein Hsp27. Cell Stress Chaperones 13:207–220

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Hinck L, Nelson WJ, Papkoff J (1994) Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin. J Cell Biol 124:729–741

    CAS  PubMed  Google Scholar 

  102. Nelson WJ, Nusse R (2004) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303:1483–1487

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Bausero MA, Bharti A, Page DT, Perez KD, Eng JW, Ordonez SL, Asea EE, Jantschitsch C, Kindas-Muegge I, Ciocca D, Asea A (2006) Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4T1 breast adenocarcinoma cell. Tumour Biol 27:17–26

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Tsai YP, Yang MH, Huang CH, Chang SY, Chen PM, Liu CJ, Teng SC, Wu KJ (2009) Interaction between HSP60 and beta-catenin promotes metastasis. Carcinogenesis 30:1049–1057

    CAS  PubMed  Google Scholar 

  105. Banz VM, Medova M, Keogh A, Furer C, Zimmer Y, Candinas D, Stroka D (2009) Hsp90 transcriptionally and post-translationally regulates the expression of NDRG1 and maintains the stability of its modifying kinase GSK3beta. Biochim Biophys Acta 1793:1597–1603

    CAS  PubMed  Google Scholar 

  106. Dou F, Chang X, Ma D (2007) Hsp90 maintains the stability and function of the tau phosphorylating kinase GSK3β. Int J Mol Sci 8:51–60

    CAS  PubMed Central  Google Scholar 

  107. Cooper LC, Prinsloo E, Edkins AL, Blatch GL (2011) Hsp90alpha/beta associates with the GSK3beta/axin1/phospho-beta-catenin complex in the human MCF-7 epithelial breast cancer model. Biochem Biophys Res Commun 413:550–554

    CAS  PubMed  Google Scholar 

  108. Kurashina R, Ohyashiki JH, Kobayashi C, Hamamura R, Zhang Y, Hirano T, Ohyashiki K (2009) Anti-proliferative activity of heat shock protein (Hsp) 90 inhibitors via beta-catenin/TCF7L2 pathway in adult T cell leukemia cells. Cancer Lett 284:62–70

    CAS  PubMed  Google Scholar 

  109. Nusse R (2013) Wnt target genes. http://www.stanford.edu/group/nusselab/cgi-bin/wnt/target_genes. Accessed 25 Oct 2013

  110. Picard D (2013) HSP90 interactors. http://www.picard.ch/downloads/Hsp90interactors.pdf. Accessed 25 Oct 2013

  111. Kawasaki H, Altieri DC, Lu C-D, Toyoda M, Tenjo T, Tanigawa N (1998) Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res 58:5071–5074

    CAS  PubMed  Google Scholar 

  112. Sarela AI, Macadam RCA, Farmery SM, Markham AF, Guillou PJ (2000) Expression of the antiapoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma. Gut 46:645–650

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Zhang T, Otevrel T, Gao Z, Gao Z, Ehrlich SM, Fields JZ, Boman BM (2001) Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer. Cancer Res 61:8664–8667

    CAS  PubMed  Google Scholar 

  114. Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, Young J, Walsh T, Ward R, Hawkins N, Beranek M, Jandik P, Benamouzig R, Jullian E, Laurent-Puig P, Olschwang S, Muller O, Hoffmann I, Rabes HM, Zietz C, Troungos C, Valavanis C, Yuen ST, Ho JW, Croke CT, O’Donoghue DP, Giaretti W, Rapallo A, Russo A, Bazan V, Tanaka M, Omura K, Azuma T, Ohkusa T, Fujimori T, Ono Y, Pauly M, Faber C, Glaesener R, de Goeij AF, Arends JW, Andersen SN, Lovig T, Breivik J, Gaudernack G, Clausen OP, De Angelis PD, Meling GI, Rognum TO, Smith R, Goh HS, Font A, Rosell R, Sun XF, Zhang H, Benhattar J, Losi L, Lee JQ, Wang ST, Clarke PA, Bell S, Quirke P, Bubb VJ, Piris J, Cruickshank NR, Morton D, Fox JC, Al-Mulla F, Lees N, Hall CN, Snary D, Wilkinson K, Dillon D, Costa J, Pricolo VE, Finkelstein SD, Thebo JS, Senagore AJ, Halter SA, Wadler S, Malik S, Krtolica K, Urosevic N (2001) Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study. Br J Cancer 85:692–696

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Smith G, Carey FA, Beattie J, Wilkie MJ, Lightfoot TJ, Coxhead J, Garner RC, Steele RJ, Wolf CR (2002) Mutations in APC, Kirsten-ras, and p53–alternative genetic pathways to colorectal cancer. Proc Natl Acad Sci U S A 99:9433–9438

    CAS  PubMed Central  PubMed  Google Scholar 

  116. Barbacid M (1990) Ras oncogenes: their role in neoplasia. Eur J Clin Invest 20:225–235

    CAS  PubMed  Google Scholar 

  117. Smith G, Bounds R, Wolf H, Steele RJ, Carey FA, Wolf CR (2010) Activating K-Ras mutations outwith ‘hotspot’ codons in sporadic colorectal tumours – implications for personalised cancer medicine. Br J Cancer 102:693–703

    CAS  PubMed Central  PubMed  Google Scholar 

  118. Ellis CA, Clark G (2000) The importance of being K-Ras. Cell Signal 12:425–434

    CAS  PubMed  Google Scholar 

  119. Azoitei N, Hoffmann CM, Ellegast JM, Ball CR, Obermayer K, Gossele U, Koch B, Faber K, Genze F, Schrader M, Kestler HA, Dohner H, Chiosis G, Glimm H, Frohling S, Scholl C (2012) Targeting of KRAS mutant tumors by HSP90 inhibitors involves degradation of STK33. J Exp Med 209:697–711

    CAS  PubMed Central  PubMed  Google Scholar 

  120. da Rocha Dias S, Friedlos F, Light Y, Springer C, Workman P, Marais R (2005) Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin. Cancer Res 65:10686–10691

    PubMed  Google Scholar 

  121. Grbovic OM, Basso AD, Sawai A, Ye Q, Friedlander P, Solit D, Rosen N (2006) V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors. Proc Natl Acad Sci U S A 103:57–62

    CAS  PubMed Central  PubMed  Google Scholar 

  122. Ghosh A, Lai C, McDonald S, Suraweera N, Sengupta N, Propper D, Dorudi S, Silver A (2013) HSP27 expression in primary colorectal cancers is dependent on mutation of KRAS and PI3K/AKT activation status and is independent of TP53. Exp Mol Pathol 94:103–108

    CAS  PubMed  Google Scholar 

  123. Sos ML, Michel K, Zander T, Weiss J, Frommolt P, Peifer M, Li D, Ullrich R, Koker M, Fischer F, Shimamura T, Rauh D, Mermel C, Fischer S, Stuckrath I, Heynck S, Beroukhim R, Lin W, Winckler W, Shah K, LaFramboise T, Moriarty WF, Hanna M, Tolosi L, Rahnenfuhrer J, Verhaak R, Chiang D, Getz G, Hellmich M, Wolf J, Girard L, Peyton M, Weir BA, Chen TH, Greulich H, Barretina J, Shapiro GI, Garraway LA, Gazdar AF, Minna JD, Meyerson M, Wong KK, Thomas RK (2009) Predicting drug susceptibility of non-small cell lung cancers based on genetic lesions. J Clin Invest 119:1727–1740

    CAS  PubMed Central  PubMed  Google Scholar 

  124. West K, Hafeez N, Mac Dougall J, Normant E, Palombella V, Fritz C (2011) Abstract 2827: activity of the proprietary Hsp90 inhibitor IPI-493 in models of colorectal cancer correlates with RAS pathway activation. Paper presented at proceedings of the 102nd annual meeting of the American Association for Cancer Research, AACR, Orlando, Philadelphia, 2–6 Apr 2011

    Google Scholar 

  125. Scholl C, Frohling S, Dunn IF, Schinzel AC, Barbie DA, Kim SY, Silver SJ, Tamayo P, Wadlow RC, Ramaswamy S, Dohner K, Bullinger L, Sandy P, Boehm JS, Root DE, Jacks T, Hahn WC, Gilliland DG (2009) Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell 137:821–834

    CAS  PubMed  Google Scholar 

  126. Babij C, Zhang Y, Kurzeja RJ, Munzli A, Shehabeldin A, Fernando M, Quon K, Kassner PD, Ruefli-Brasse AA, Watson VJ, Fajardo F, Jackson A, Zondlo J, Sun Y, Ellison AR, Plewa CA, San MT, Robinson J, McCarter J, Schwandner R, Judd T, Carnahan J, Dussault I (2011) STK33 kinase activity is nonessential in KRAS-dependent cancer cells. Cancer Res 71:5818–5826

    CAS  PubMed  Google Scholar 

  127. Luo T, Masson K, Jaffe JD, Silkworth W, Ross NT, Scherer CA, Scholl C, Frohling S, Carr SA, Stern AM, Schreiber SL, Golub TR (2012) STK33 kinase inhibitor BRD-8899 has no effect on KRAS-dependent cancer cell viability. Proc Natl Acad Sci U S A 109:2860–2865

    CAS  PubMed Central  PubMed  Google Scholar 

  128. Safaee Ardekani G, Jafarnejad SM, Tan L, Saeedi A, Li G (2012) The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PLoS One 7:e47054

    PubMed Central  PubMed  Google Scholar 

  129. De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, Biesmans B, Van Laethem J-L, Peeters M, Humblet Y, Van Cutsem E, Tejpar S (2008) KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19:508–515

    PubMed  Google Scholar 

  130. Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26:5705–5712

    PubMed  Google Scholar 

  131. Babchia N, Calipel A, Mouriaux F, Faussat AM, Mascarelli F (2008) 17-AAG and 17-DMAG-induced inhibition of cell proliferation through B-Raf downregulation in WT B-Raf-expressing uveal melanoma cell lines. Invest Ophthalmol Vis Sci 49:2348–2356

    PubMed  Google Scholar 

  132. Wu X, Marmarelis ME, Hodi FS (2013) Activity of the heat shock protein 90 inhibitor ganetespib in melanoma. PLoS One 8:e56134

    CAS  PubMed Central  PubMed  Google Scholar 

  133. Banerji U, Affolter A, Judson I, Marais R, Workman P (2008) BRAF and NRAS mutations in melanoma: potential relationships to clinical response to HSP90 inhibitors. Mol Cancer Ther 7:737–739

    CAS  PubMed  Google Scholar 

  134. Pacey S, Gore M, Chao D, Banerji U, Larkin J, Sarker S, Owen K, Asad Y, Raynaud F, Walton M, Judson I, Workman P, Eisen T (2012) A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma. Invest New Drugs 30:341–349

    CAS  PubMed  Google Scholar 

  135. Solit DB, Osman I, Polsky D, Panageas KS, Daud A, Goydos JS, Teitcher J, Wolchok JD, Germino FJ, Krown SE, Coit D, Rosen N, Chapman PB (2008) Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with metastatic melanoma. Clin Cancer Res 14:8302–8307

    CAS  PubMed Central  PubMed  Google Scholar 

  136. Lane DP (1992) Cancer. p53, guardian of the genome. Nature 358:15–16

    CAS  PubMed  Google Scholar 

  137. Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323–331

    CAS  PubMed  Google Scholar 

  138. May P, May E (1999) Twenty years of p53 research: structural and functional aspects of the p53 protein. Oncogene 18:7621–7636

    CAS  PubMed  Google Scholar 

  139. Oren M, Rotter V (1999) Introduction: p53–the first twenty years. Cell Mol Life Sci 55:9–11

    CAS  PubMed  Google Scholar 

  140. Naccarati A, Polakova V, Pardini B, Vodickova L, Hemminki K, Kumar R, Vodicka P (2012) Mutations and polymorphisms in TP53 gene–an overview on the role in colorectal cancer. Mutagenesis 27:211–218

    CAS  PubMed  Google Scholar 

  141. Soussi T, Kato S, Levy PP, Ishioka C (2005) Reassessment of the TP53 mutation database in human disease by data mining with a library of TP53 missense mutations. Hum Mutat 25:6–17

    CAS  PubMed  Google Scholar 

  142. Iacopetta B, Russo A, Bazan V, Dardanoni G, Gebbia N, Soussi T, Kerr D, Elsaleh H, Soong R, Kandioler D, Janschek E, Kappel S, Lung M, Leung C-SS, Ko JM, Yuen S, Ho J, Leung SY, Crapez E, Duffour J, Ychou M, Leahy DT, O’Donoghue DP, Agnese V, Cascio S, Di Fede G, Chieco-Bianchi L, Bertorelle R, Belluco C, Giaretti W, Castagnola P, Ricevuto E, Ficorella C, Bosari S, Arizzi CD, Miyaki M, Onda M, Kampman E, Diergaarde B, Royds J, Lothe RA, Diep CB, Meling GI, Ostrowski J, Trzeciak L, Guzińska-Ustymowicz K, Zalewski B, Capellá GM, Moreno V, Peinado MA, Lönnroth C, Lundholm K, Sun XF, Jansson A, Bouzourene H, Hsieh L-L, Tang R, Smith DR, Allen-Mersh TG, Khan ZAJ, Shorthouse AJ, Silverman ML, Kato S, Ishioka C (2006) Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study. Ann Oncol 17:842–847

    CAS  PubMed  Google Scholar 

  143. Pinhasi-Kimhi O, Michalovitz D, Ben-Zeev A, Oren M (1986) Specific interaction between the p53 cellular tumour antigen and major heat shock proteins. Nature 320:182–184

    CAS  PubMed  Google Scholar 

  144. Whitesell L, Sutphin PD, Pulcini EJ, Martinez JD, Cook PH (1998) 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

    CAS  PubMed Central  PubMed  Google Scholar 

  145. Dai C, Whitesell L, Rogers AB, Lindquist S (2007) Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 130:1005–1018

    CAS  PubMed Central  PubMed  Google Scholar 

  146. Gestl EE, Anne Bottger S (2012) Cytoplasmic sequestration of the tumor suppressor p53 by a heat shock protein 70 family member, mortalin, in human colorectal adenocarcinoma cell lines. Biochem Biophys Res Commun 423:411–416

    CAS  PubMed  Google Scholar 

  147. Kaul SC, Deocaris CC, Wadhwa R (2007) Three faces of mortalin: a housekeeper, guardian and killer. Exp Gerontol 42:263–274

    CAS  PubMed  Google Scholar 

  148. Hagn F, Lagleder S, Retzlaff M, Rohrberg J, Demmer O, Richter K, Buchner J, Kessler H (2011) Structural analysis of the interaction between Hsp90 and the tumor suppressor protein p53. Nat Struct Mol Biol 18:1086–1093

    CAS  PubMed  Google Scholar 

  149. Park SJ, Kostic M, Dyson HJ (2011) Dynamic interaction of Hsp90 with its client protein p53. J Mol Biol 411:158–173

    CAS  PubMed Central  PubMed  Google Scholar 

  150. Blagosklonny MV, Toretsky J, Bohen S, Neckers L (1996) Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90. Proc Natl Acad Sci U S A 93:8379–8383

    CAS  PubMed Central  PubMed  Google Scholar 

  151. Vaseva AV, Yallowitz AR, Marchenko ND, Xu S, Moll UM (2011) Blockade of Hsp90 by 17AAG antagonizes MDMX and synergizes with Nutlin to induce p53-mediated apoptosis in solid tumors. Cell Death Dis 2:e156

    CAS  PubMed Central  PubMed  Google Scholar 

  152. Ayrault O, Godeny MD, Dillon C, Zindy F, Fitzgerald P, Roussel MF, Beere HM (2009) Inhibition of Hsp90 via 17-DMAG induces apoptosis in a p53-dependent manner to prevent medulloblastoma. Proc Natl Acad Sci U S A 106:17037–17042

    CAS  PubMed Central  PubMed  Google Scholar 

  153. Masi G, Loupakis F, Pollina L, Vasile E, Cupini S, Ricci S, Brunetti IM, Ferraldeschi R, Naso G, Filipponi F, Pietrabissa A, Goletti O, Baldi G, Fornaro L, Andreuccetti M, Falcone A (2009) Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) followed by radical surgery of metastases. Ann Surg 249:420–425

    PubMed  Google Scholar 

  154. Bartlett DL, Chu E (2012) Can metastatic colorectal cancer be cured? Oncology (Williston Park) 26:266–275

    Google Scholar 

  155. Longley DB, Harkin DP, Johnston PG (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3:330–338

    CAS  PubMed  Google Scholar 

  156. Arbuck S (1989) Overview of clinical trials using 5-fluorouracil and leucovorin for the treatment of colorectal cancer. Cancer 63:1036–1044

    CAS  PubMed  Google Scholar 

  157. Copur S, Aiba K, Drake JC, Allegra CJ, Chu E (1995) Thymidylate synthase gene amplification in human colon cancer cell lines resistant to 5-fluorouracil. Biochem Pharmacol 49:1419–1426

    CAS  PubMed  Google Scholar 

  158. Johnston PG, Lenz HJ, Leichman CG, Danenberg KD, Allegra CJ, Danenberg PV, Leichman L (1995) Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Res 55:1407–1412

    CAS  PubMed  Google Scholar 

  159. Lee J-H, Park J-H, Jung Y, Kim J-H, Jong H-S, Kim T-Y, Bang Y-J (2006) Histone deacetylase inhibitor enhances 5-fluorouracil cytotoxicity by down-regulating thymidylate synthase in human cancer cells. Mol Cancer Ther 5:3085–3095

    CAS  PubMed  Google Scholar 

  160. Grivicich I, Regner A, Zanoni C, Correa L, Jotz G, Henriques J, Schwartsmann G, Rocha A (2007) Hsp70 response to 5-fluorouracil treatment in human colon cancer cell lines. Int J Colorectal Dis 22:1201–1208

    PubMed  Google Scholar 

  161. Takechi T, Koizumi K, Tsujimoto H, Fukushima M (2001) Screening of differentially expressed genes in 5-fluorouracil-resistant human astrointestinal tumor cells. Cancer Sci 92:696–703

    CAS  Google Scholar 

  162. Ang CW, Tweedle EM, Neoptolemos JP, Rooney PS, Costello E (2010) Tumour heat shock protein (HSP)-27 expression as predictive factor of patient response to adjuvant 5-fluorouracil in Dukes’ C colorectal cancer. Br J Surg 97:83–83

    Google Scholar 

  163. Tsuruta M, Nishibori H, Hasegawa H, Ishii Y, Endo T, Kubota T, Kitajima M, Kitagawa Y (2008) Heat shock protein 27, a novel regulator of 5-fluorouracil resistance in colon cancer. Oncol Rep 20:1165–1172

    CAS  PubMed  Google Scholar 

  164. Raymond E, Faivre S, Chaney S, Woynarowski J, Cvitkovic E (2002) Cellular and molecular pharmacology of oxaliplatin1. Mol Cancer Ther 1:227–235

    CAS  PubMed  Google Scholar 

  165. Vaisman A, Varchenko M, Umar A, Kunkel TA, Risinger JI, Barrett JC, Hamilton TC, Chaney SG (1998) The role of hMLH1, hMSH3, and hMSH6 defects in cisplatin and oxaliplatin resistance: correlation with replicative bypass of platinum-DNA adducts. Cancer Res 58:3579–3585

    CAS  PubMed  Google Scholar 

  166. Rakitina TV, Vasilevskaya IA, O’Dwyer PJ (2003) Additive interaction of oxaliplatin and 17-allylamino-17-demethoxygeldanamycin in colon cancer cell lines results from inhibition of nuclear factor kappa B signaling. Cancer Res 63:8600–8605

    CAS  PubMed  Google Scholar 

  167. Rakitina TV, Vasilevskaya IA, O’Dwyer PJ (2007) Inhibition of G1/S transition potentiates oxaliplatin-induced cell death in colon cancer cell lines. Biochem Pharmacol 73:1715–1726

    CAS  PubMed  Google Scholar 

  168. Moser C, Lang SA, Kainz S, Gaurnann A, Fichtner-Feig S, Koehl GE, Schlitt HJ, Geissler EK, Stoeltzing O (2007) Blocking heat shock protein-90 inhibits the invasive properties and hepatic growth of human colon cancer cells and improves the efficacy of oxaliplatin in p53-deficient colon cancer tumors in vivo. Mol Cancer Ther 6:2868–2878

    CAS  PubMed  Google Scholar 

  169. Park KA, Byun HS, Won M, Yang KJ, Shin S, Piao L, Kim JM, Yoon WH, Junn E, Park J, Seok JH, Hur GM (2007) Sustained activation of protein kinase C downregulates nuclear factor-kappaB signaling by dissociation of IKK-gamma and Hsp90 complex in human colonic epithelial cells. Carcinogenesis 28:71–80

    CAS  PubMed  Google Scholar 

  170. Lee KH, Jang Y, Chung JH (2010) Heat shock protein 90 regulates IkappaB kinase complex and NF-kappaB activation in angiotensin II-induced cardiac cell hypertrophy. Exp Mol Med 42:703–711

    CAS  PubMed Central  PubMed  Google Scholar 

  171. Shimp SK 3rd, Parson CD, Regna NL, Thomas AN, Chafin CB, Reilly CM, Nichole Rylander M (2012) HSP90 inhibition by 17-DMAG reduces inflammation in J774 macrophages through suppression of Akt and nuclear factor-kappaB pathways. Inflamm Res 61:521–533

    CAS  PubMed  Google Scholar 

  172. Walsby E, Pearce L, Burnett AK, Fegan C, Pepper C (2012) The Hsp90 inhibitor NVP-AUY922-AG inhibits NF-kappaB signaling, overcomes microenvironmental cytoprotection and is highly synergistic with fludarabine in primary CLL cells. Oncotarget 3:525–534

    PubMed Central  PubMed  Google Scholar 

  173. Rothenberg ML (1997) Topoisomerase I inhibitors: review and update. Ann Oncol 8:837–855

    CAS  PubMed  Google Scholar 

  174. Chen AY, Liu LF (1994) Mechanisms of resistance to topoisomerase inhibitors. Cancer Treat Res 73:263–281

    CAS  PubMed  Google Scholar 

  175. Tse AN, Rendahl KG, Sheikh T, Cheema H, Aardalen K, Embry M, Ma S, Moler EJ, Ni ZJ, Lopes de Menezes DE, Hibner B, Gesner TG, Schwartz GK (2007) CHIR-124, a novel potent inhibitor of Chk1, potentiates the cytotoxicity of topoisomerase I poisons in vitro and in vivo. Clin Cancer Res 13:591–602

    CAS  PubMed  Google Scholar 

  176. Tse AN, Klimstra DS, Gonen M, Shah M, Sheikh T, Sikorski R, Carvajal R, Mui J, Tipian C, O’Reilly E, Chung K, Maki R, Lefkowitz R, Brown K, Manova-Todorova K, Wu N, Egorin MJ, Kelsen D, Schwartz GK (2008) A phase 1 dose-escalation study of irinotecan in combination with 17-allylamino-17-demethoxygeldanamycin in patients with solid tumors. Clin Cancer Res 14:6704–6711

    CAS  PubMed Central  PubMed  Google Scholar 

  177. Choi DH, Ha JS, Lee WH, Song JK, Kim GY, Park JH, Cha HJ, Lee BJ, Park JW (2007) Heat shock protein 27 is associated with irinotecan resistance in human colorectal cancer cells. FEBS Lett 581:1649–1656

    CAS  PubMed  Google Scholar 

  178. Wainberg ZA, Anghel A, Rogers AM, Desai AJ, Kalous O, Conklin D, Ayala R, O’Brien NA, Quadt C, Akimov M, Slamon DJ, Finn RS (2013) Inhibition of HSP90 with AUY922 induces synergy in HER2-amplified trastuzumab-resistant breast and gastric cancer. Mol Cancer Ther 12:509–519

    CAS  PubMed  Google Scholar 

  179. Modi S, Stopeck A, Linden H, Solit D, Chandarlapaty S, Rosen N, D’Andrea G, Dickler M, Moynahan ME, Sugarman S, Ma W, Patil S, Norton L, Hannah AL, Hudis C (2011) HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin Cancer Res 17:5132–5139

    CAS  PubMed  Google Scholar 

  180. Tsang RY, Finn RS (2012) Beyond trastuzumab: novel therapeutic strategies in HER2-positive metastatic breast cancer. Br J Cancer 106:6–13

    CAS  PubMed Central  PubMed  Google Scholar 

  181. Niu G, Cai W, Chen K, Chen X (2008) Non-invasive PET imaging of EGFR degradation induced by a heat shock protein 90 inhibitor. Mol Imaging Biol 10:99–106

    PubMed  Google Scholar 

  182. Zaczek A, Brandt B, Bielawski KP (2005) The diverse signaling network of EGFR, HER2, HER3 and HER4 tyrosine kinase receptors and the consequences for therapeutic approaches. Histol Histopathol 20:1005–1015

    CAS  PubMed  Google Scholar 

  183. Citri A, Kochupurakkal BS, Yarden Y (2004) The achilles heel of ErbB-2/HER2: regulation by the Hsp90 chaperone machine and potential for pharmacological intervention. Cell Cycle 3:51–60

    CAS  PubMed  Google Scholar 

  184. Ahsan A, Ramanand SG, Whitehead C, Hiniker SM, Rehemtulla A, Pratt WB, Jolly S, Gouveia C, Truong K, Van Waes C, Ray D, Lawrence TS, Nyati MK (2012) Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors. Neoplasia 14:670–677

    CAS  PubMed Central  PubMed  Google Scholar 

  185. Lavictoire SJ, Parolin DA, Klimowicz AC, Kelly JF, Lorimer IA (2003) Interaction of Hsp90 with the nascent form of the mutant epidermal growth factor receptor EGFRvIII. J Biol Chem 278:5292–5299

    CAS  PubMed  Google Scholar 

  186. Blok EJ, Kuppen PJ, van Leeuwen JE, Sier CF (2013) Cytoplasmic overexpression of HER2: a key factor in colorectal cancer. Clin Med Insights Oncol 7:41–51

    CAS  PubMed Central  PubMed  Google Scholar 

  187. Ferrara N, Hillan KJ, Gerber HP, Novotny W (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3:391–400

    CAS  PubMed  Google Scholar 

  188. Bruns AF, Yuldasheva N, Latham AM, Bao L, Pellet-Many C, Frankel P, Stephen SL, Howell GJ, Wheatcroft SB, Kearney MT, Zachary IC, Ponnambalam S (2012) A heat-shock protein axis regulates VEGFR2 proteolysis, blood vessel development and repair. PLoS One 7:e48539

    CAS  PubMed Central  PubMed  Google Scholar 

  189. Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM (2002) Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway. J Biol Chem 277:29936–29944

    CAS  PubMed  Google Scholar 

  190. Liu YV, Baek JH, Zhang H, Diez R, Cole RN, Semenza GL (2007) RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha. Mol Cell 25:207–217

    PubMed Central  PubMed  Google Scholar 

  191. Ganji PN, Park W, Wen J, Mahaseth H, Landry J, Farris AB, Willingham F, Sullivan PS, Proia DA, El-Hariry I, Taliaferro-Smith L, Diaz R, El-Rayes BF (2013) Antiangiogenic effects of ganetespib in colorectal cancer mediated through inhibition of HIF-1alpha and STAT-3. Angiogenesis 16:903–917

    CAS  PubMed  Google Scholar 

  192. Moser C, Lang SA, Hackl C, Wagner C, Scheiffert E, Schlitt HJ, Geissler EK, Stoeltzing O (2012) Targeting HSP90 by the novel inhibitor NVP-AUY922 reduces growth and angiogenesis of pancreatic cancer. Anticancer Res 32:2551–2561

    CAS  PubMed  Google Scholar 

  193. Miyauchi T, Miyata M, Ikeda Y, Akasaki Y, Hamada N, Shirasawa T, Furusho Y, Tei C (2012) Waon therapy upregulates Hsp90 and leads to angiogenesis through the Akt-endothelial nitric oxide synthase pathway in mouse hindlimb ischemia. Circ J 76:1712–1721

    CAS  PubMed  Google Scholar 

  194. Kampinga HH, Brunsting JF, Stege GJ, Burgman PW, Konings AW (1995) Thermal protein denaturation and protein aggregation in cells made thermotolerant by various chemicals: role of heat shock proteins. Exp Cell Res 219:536–546

    CAS  PubMed  Google Scholar 

  195. Kampinga HH, Brunsting JF, Stege GJ, Konings AW, Landry J (1994) Cells overexpressing Hsp27 show accelerated recovery from heat-induced nuclear protein aggregation. Biochem Biophys Res Commun 204:1170–1177

    CAS  PubMed  Google Scholar 

  196. Mao RF, Rubio V, Chen H, Bai L, Mansour OC, Shi ZZ (2013) OLA1 protects cells in heat shock by stabilizing HSP70. Cell Death Dis 4:e491

    CAS  PubMed Central  PubMed  Google Scholar 

  197. Gandhi N, Wild AT, Chettiar ST, Aziz K, Kato Y, Gajula RP, Williams RD, Cades JA, Annadanam A, Song D, Zhang Y, Hales RK, Herman JM, Armour E, DeWeese TL, Schaeffer EM, Tran PT (2013) Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells. Cancer Biol Ther 14:347–356

    CAS  PubMed Central  PubMed  Google Scholar 

  198. Milanovic D, Firat E, Grosu AL, Niedermann G (2013) Increased radiosensitivity and radiothermosensitivity of human pancreatic MIA PaCa-2 and U251 glioblastoma cell lines treated with the novel Hsp90 inhibitor NVP-HSP990. Radiat Oncol 8:42

    PubMed Central  PubMed  Google Scholar 

  199. Hartmann S, Gunther N, Biehl M, Katzer A, Kuger S, Worschech E, Sukhorukov VL, Krohne G, Zimmermann H, Flentje M, Djuzenova CS (2013) Hsp90 inhibition by NVP-AUY922 and NVP-BEP800 decreases migration and invasion of irradiated normoxic and hypoxic tumor cell lines. Cancer Lett 331:200–210

    CAS  PubMed  Google Scholar 

  200. Niewidok N, Wack LJ, Schiessl S, Stingl L, Katzer A, Polat B, Sukhorukov VL, Flentje M, Djuzenova CS (2012) Hsp90 inhibitors NVP-AUY922 and NVP-BEP800 may exert a significant radiosensitization on tumor cells along with a cell type-specific cytotoxicity. Transl Oncol 5:356–369

    PubMed Central  PubMed  Google Scholar 

  201. Testori A, Richards J, Whitman E, Mann GB, Lutzky J, Camacho L, Parmiani G, Tosti G, Kirkwood JM, Hoos A, Yuh L, Gupta R, Srivastava PK (2008) Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician’s choice of treatment for stage IV melanoma: the C-100-21 Study Group. J Clin Oncol 26:955–962

    CAS  PubMed  Google Scholar 

  202. Wood C, Srivastava P, Bukowski R, Lacombe L, Gorelov AI, Gorelov S, Mulders P, Zielinski H, Hoos A, Teofilovici F, Isakov L, Flanigan R, Figlin R, Gupta R, Escudier B (2008) An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet 372:145–154

    CAS  PubMed  Google Scholar 

  203. Young M, Ordonez L, Clarke AR (2013) What are the best routes to effectively model human colorectal cancer? Mol Oncol 7:178–189

    PubMed  Google Scholar 

  204. Alarcon SV, Mollapour M, Lee MJ, Tsutsumi S, Lee S, Kim YS, Prince T, Apolo AB, Giaccone G, Xu W, Neckers LM, Trepel JB (2012) Tumor-intrinsic and tumor-extrinsic factors impacting hsp90- targeted therapy. Curr Mol Med 12:1125–1141

    CAS  PubMed Central  PubMed  Google Scholar 

  205. Reitsma DJ, Combest AJ (2012) Challenges in the development of an autologous heat shock protein based anti-tumor vaccine. Hum Vaccin Immunother 8:1152–1155

    CAS  PubMed Central  PubMed  Google Scholar 

  206. Bagatell R, Paine-Murrieta GD, Taylor CW, Pulcini EJ, Akinaga S, Benjamin IJ, Whitesell L (2000) Induction of a heat shock factor 1-dependent stress response alters the cytotoxic activity of hsp90-binding agents. Clin Cancer Res 6:3312–3318

    CAS  PubMed  Google Scholar 

  207. Conde R, Belak ZR, Nair M, O’Carroll RF, Ovsenek N (2009) Modulation of Hsf1 activity by novobiocin and geldanamycin. Biochem Cell Biol 87:845–851

    CAS  PubMed  Google Scholar 

  208. Donnelly A, Blagg BS (2008) Novobiocin and additional inhibitors of the Hsp90 C-terminal nucleotide-binding pocket. Curr Med Chem 15:2702–2717

    CAS  PubMed Central  PubMed  Google Scholar 

  209. Zhao H, Donnelly AC, Kusuma BR, Brandt GE, Brown D, Rajewski RA, Vielhauer G, Holzbeierlein J, Cohen MS, Blagg BS (2011) Engineering an antibiotic to fight cancer: optimization of the novobiocin scaffold to produce anti-proliferative agents. J Med Chem 54:3839–3853

    CAS  PubMed Central  PubMed  Google Scholar 

  210. Callahan MK, Garg M, Srivastava PK (2008) Heat-shock protein 90 associates with N-terminal extended peptides and is required for direct and indirect antigen presentation. Proc Natl Acad Sci U S A 105:1662–1667

    CAS  PubMed Central  PubMed  Google Scholar 

  211. Tsuji T, Matsuzaki J, Caballero OL, Jungbluth AA, Ritter G, Odunsi K, Old LJ, Gnjatic S (2012) Heat shock protein 90-mediated peptide-selective presentation of cytosolic tumor antigen for direct recognition of tumors by CD4(+) T cells. J Immunol 188:3851–3858

    CAS  PubMed  Google Scholar 

  212. Bae J, Mitsiades C, Tai YT, Bertheau R, Shammas M, Batchu RB, Li C, Catley L, Prabhala R, Anderson KC, Munshi NC (2007) Phenotypic and functional effects of heat shock protein 90 inhibition on dendritic cell. J Immunol 178:7730–7737

    CAS  PubMed  Google Scholar 

  213. Rao A, Taylor JL, Chi-Sabins N, Kawabe M, Gooding WE, Storkus WJ (2012) Combination therapy with HSP90 inhibitor 17-DMAG reconditions the tumor microenvironment to improve recruitment of therapeutic T cells. Cancer Res 72:3196–3206

    CAS  PubMed Central  PubMed  Google Scholar 

  214. Ciocca DR, Frayssinet P, Cuello-Carrion FD (2007) A pilot study with a therapeutic vaccine based on hydroxyapatite ceramic particles and self-antigens in cancer patients. Cell Stress Chaperones 12:33–43

    CAS  PubMed Central  PubMed  Google Scholar 

  215. Kovalchin JT, Murthy AS, Horattas MC, Guyton DP, Chandawarkar RY (2001) Determinants of efficacy of immunotherapy with tumor-derived heat shock protein gp96. Cancer Immun 1:7

    CAS  PubMed  Google Scholar 

  216. Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM (2006) Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 244:254–259

    PubMed Central  PubMed  Google Scholar 

  217. Sequist LV, Gettinger S, Senzer NN, Martins RG, Janne PA, Lilenbaum R, Gray JE, Iafrate AJ, Katayama R, Hafeez N, Sweeney J, Walker JR, Fritz C, Ross RW, Grayzel D, Engelman JA, Borger DR, Paez G, Natale R (2010) Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol 28:4953–4960

    CAS  PubMed  Google Scholar 

  218. Tang YC, Williams BR, Siegel JJ, Amon A (2011) Identification of aneuploidy-selective antiproliferation compounds. Cell 144:499–512

    CAS  PubMed Central  PubMed  Google Scholar 

  219. Eichler K, Zangos S, Mack MG, Hammerstingl R, Gruber-Rouh T, Gallus C, Vogl TJ (2012) First human study in treatment of unresectable liver metastases from colorectal cancer with irinotecan-loaded beads (DEBIRI). Int J Oncol 41:1213–1220

    CAS  PubMed Central  PubMed  Google Scholar 

  220. Richardson AJ, Laurence JM, Lam VW (2013) Transarterial chemoembolization with irinotecan beads in the treatment of colorectal liver metastases: systematic review. J Vasc Interv Radiol 24:1209–1217

    PubMed  Google Scholar 

  221. Cosimelli M, Golfieri R, Cagol PP, Carpanese L, Sciuto R, Maini CL, Mancini R, Sperduti I, Pizzi G, Diodoro MG, Perrone M, Giampalma E, Angelelli B, Fiore F, Lastoria S, Bacchetti S, Gasperini D, Geatti O, Izzo F (2010) Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases. Br J Cancer 103:324–331

    CAS  PubMed Central  PubMed  Google Scholar 

  222. Nace GW, Steel JL, Amesur N, Zajko A, Nastasi BE, Joyce J, Sheetz M, Gamblin TC (2011) Yttrium-90 radioembolization for colorectal cancer liver metastases: a single institution experience. Int J Surg Oncol 2011:571261

    PubMed Central  PubMed  Google Scholar 

  223. Santhosh PB, Ulrih NP (2013) Multifunctional superparamagnetic iron oxide nanoparticles: promising tools in cancer theranostics. Cancer Lett 336:8–17

    CAS  PubMed  Google Scholar 

  224. Veiseh O, Kievit FM, Fang C, Mu N, Jana S, Leung MC, Mok H, Ellenbogen RG, Park JO, Zhang M (2010) Chlorotoxin bound magnetic nanovector tailored for cancer cell targeting, imaging, and siRNA delivery. Biomaterials 31:8032–8042

    CAS  PubMed Central  PubMed  Google Scholar 

  225. Bausero MA, Oddone N, Lima E, Benech JC (2013) Supraparamagnetic iron oxide nanoparticles (SPIONs) as a novel siRNA-Hsp27 delivery system for cancer treatment. Paper presented at VI international congress on stress proteins in biology and medicine, Sheffield, 18–22 Aug 2013

    Google Scholar 

  226. Tse AN, Sheikh TN, Alan H, Chou TC, Schwartz GK (2009) 90-kDa heat shock protein inhibition abrogates the topoisomerase I poison-induced G2/M checkpoint in p53-null tumor cells by depleting Chk1 and Wee1. Mol Pharmacol 75:124–133

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chester Center for Stress Research, University of Chester, Parkgate Road, Chester, CH1 4BJ, UK

    Sheah Lin Lee & John H. H. Williams

  2. School of Healthcare Science, Manchester Metropolitan University, John Dalton Building, Oxford Road, Manchester, M1 5GD, UK

    Nina Claire Dempsey-Hibbert

  3. Countess of Chester Hospital NHS Foundation Trust, Countess of Chester Health Park, Liverpool Road, Chester, CH2 1UL, UK

    Dale Vimalachandran, Terence David Wardle & Paul Sutton

Authors
  1. Sheah Lin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nina Claire Dempsey-Hibbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dale Vimalachandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Terence David Wardle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul Sutton
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John H. H. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John H. H. Williams .

Editor information

Editors and Affiliations

  1. Professor and VD for Research Innovations, Deanship for Scientific Research,, University of Dammam, Dammam, Saudi Arabia

    Alexzander A.A. Asea

  2. Deanship for Scientific Research and Preventive Dental Sciences Department, College of Dentistry, University of Dammam, Dammam, Saudi Arabia

    Naif N. Almasoud

  3. Gastrointestinal Translational Research, Center for Radiation Oncology Research, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Sunil Krishnan

  4. Department of Microbiology, Immunology & Biochemistry, Morehouse School of Medicine, Atlanta, Georgia, USA

    Punit Kaur

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Lee, S.L., Dempsey-Hibbert, N.C., Vimalachandran, D., Wardle, T.D., Sutton, P., Williams, J.H.H. (2015). Targeting Heat Shock Proteins in Colorectal Cancer. In: Asea, A., Almasoud, N., Krishnan, S., Kaur, P. (eds) Heat Shock Protein-Based Therapies. Heat Shock Proteins, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-17211-8_17

Download citation

Publish with us

Policies and ethics

Search

Navigation