Impact of heat-shock protein 90 on cancer metastasis

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

• 1  Bacac M, Stamenkovic I: Metastatic cancer cell. Annu. Rev. Pathol.3,221–247 (2008).
  Medline CASGoogle Scholar
• 2  Weigelt B, Peterse JL, van ’t Veer LJ: Breast cancer metastasis: markers and models. Nat. Rev. Cancer5,591–602 (2005).
  Medline CASGoogle Scholar
• 3  Romanucci M, Marinelli A, Sarli G, Della Salda L: Heat shock protein expression in canine malignant mammary tumours. BMC Cancer6,171 (2006).
  MedlineGoogle Scholar
• 4  Kamal A, Thao L, Sensintaffar J et al.: A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature425,407–410 (2003).
  Medline CASGoogle Scholar
• 5  Neckers L: Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol. Med.8,S55–S61 (2002).
  Medline CASGoogle Scholar
• 6  Pratt WB, Toft DO: Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp. Biol. Med. (Maywood)228,111–133 (2003).
  Medline CASGoogle Scholar
• 7  Pearl LH, Prodromou C: Structure and mechanism of the Hsp90 molecular chaperone machinery. Annu. Rev. Biochem.75,271–294 (2006).▪ Comprehensive review of Hsp90 structure and function.
  Medline CASGoogle Scholar
• 8  Taldone T, Gozman A, Maharaj R, Chiosis G: Targeting Hsp90: small-molecule inhibitors and their clinical development. Curr. Opin. Pharmacol.8,370–374 (2008).▪ Good current summary of Hsp90 inhibitors in clinical development.
  Medline CASGoogle Scholar
• 9  Sharp S, Workman P: Inhibitors of the HSP90 molecular chaperone: current status. Adv. Cancer Res.95,323–348 (2006).
  Medline CASGoogle Scholar
• 10  Stebbins 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 antitumor agent. Cell89,239–250 (1997).▪▪ Describes the first co-crystallization of Hsp90 with geldanamycin.
  Medline CASGoogle Scholar
• 11  Grenert JP, Sullivan WP, Fadden P et al.: The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation. J. Biol. Chem.272,23843–23850 (1997).
  Medline CASGoogle Scholar
• 12  Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM: 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. USA91,8324–8328 (1994).▪▪ The initial identification of geldanamycin as an Hsp90 inhibitor.
  Medline CASGoogle Scholar
• 13  Workman P, Burrows F, Neckers L, Rosen N: Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann. NY Acad. Sci.1113,202–216 (2007).
  Medline CASGoogle Scholar
• 14  Felding-Habermann B: Integrin adhesion receptors in tumor metastasis. Clin. Exp. Metastasis20,203–213 (2003).
  Medline CASGoogle Scholar
• 15  Arnaout MA, Goodman SL, Xiong JP: Structure and mechanics of integrin-based cell adhesion. Curr. Opin. Cell Biol.19,495–507 (2007).
  Medline CASGoogle Scholar
• 16  Mitra SK, Hanson DA, Schlaepfer DD: Focal adhesion kinase: in command and control of cell motility. Nat. Rev. Mol. Cell Biol.6,56–68 (2005).
  Medline CASGoogle Scholar
• 17  McLean GW, Carragher NO, Avizienyte E et al.: The role of focal-adhesion kinase in cancer – a new therapeutic opportunity. Nat. Rev. Cancer5,505–515 (2005).
  Medline CASGoogle Scholar
• 18  Ochel HJ, Schulte TW, Nguyen P, Trepel J, Neckers L: The benzoquinone ansamycin geldanamycin stimulates proteolytic degradation of focal adhesion kinase. Mol. Genet. Metab.66,24–30 (1999).
  Medline CASGoogle Scholar
• 19  Rousseau S, Houle F, Kotanides H et al.: Vascular endothelial growth factor (VEGF)-driven actin-based motility is mediated by VEGFR2 and requires concerted activation of stress-activated protein kinase 2 (SAPK2/p38) and geldanamycin-sensitive phosphorylation of focal adhesion kinase. J. Biol. Chem.275,10661–10672 (2000).
  Medline CASGoogle Scholar
• 20  Masson-Gadais B, Houle F, Laferriere J, Huot J: Integrin αvβ3, requirement for VEGFR2-mediated activation of SAPK2/p38 and for Hsp90-dependent phosphorylation of focal adhesion kinase in endothelial cells activated by VEGF. Cell Stress Chaperones8,37–52 (2003).
  Medline CASGoogle Scholar
• 21  Koga F, Tsutsumi S, Neckers LM: Low dose geldanamycin inhibits hepatocyte growth factor and hypoxia-stimulated invasion of cancer cells. Cell Cycle6,1393–1402 (2007).
  Medline CASGoogle Scholar
• 22  Hannigan G, Troussard AA, Dedhar S: Integrin-linked kinase: a cancer therapeutic target unique among its ILK. Nat. Rev. Cancer5,51–63 (2005).
  Medline CASGoogle Scholar
• 23  Aoyagi Y, Fujita N, Tsuruo T: Stabilization of integrin-linked kinase by binding to Hsp90. Biochem. Biophys. Res. Commun.331,1061–1068 (2005).
  Medline CASGoogle Scholar
• 24  Yamazaki D, Kurisu S, Takenawa T: Regulation of cancer cell motility through actin reorganization. Cancer Sci.96,379–386 (2005).
  Medline CASGoogle Scholar
• 25  Overall CM, Lopez-Otin C: Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat. Rev. Cancer2,657–672 (2002).
  Medline CASGoogle Scholar
• 26  Anand-Apte B, Zetter B: Signaling mechanisms in growth factor-stimulated cell motility. Stem Cells15,259–267 (1997).
  Medline CASGoogle Scholar
• 27  Yu D, Hung MC: Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene19,6115–6121 (2000).
  Medline CASGoogle Scholar
• 28  Santin AD, Bellone S, Gokden M et al.: Overexpression of HER-2/neu in uterine serous papillary cancer. Clin. Cancer Res.8,1271–1279 (2002).
  Medline CASGoogle Scholar
• 29  Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science235,177–182 (1987).
  Medline CASGoogle Scholar
• 30  Ross JS, Fletcher JA: The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Stem Cells16,413–428 (1998).
  Medline CASGoogle Scholar
• 31  Chavany C, Mimnaugh E, Miller P et al.: p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2. J. Biol. Chem.271,4974–4977 (1996).
  Medline CASGoogle Scholar
• 32  Xu W, Mimnaugh E, Rosser MF et al.: Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90. J. Biol. Chem.276,3702–3708 (2001).
  Medline CASGoogle Scholar
• 33  Miller P, DiOrio C, Moyer M et al.: Depletion of the erbB-2 gene product p185 by benzoquinoid ansamycins. Cancer Res.54,2724–2730 (1994).
  Medline CASGoogle Scholar
• 34  Citri A, Alroy I, Lavi S et al.: Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy. EMBO J.21,2407–2417 (2002).
  Medline CASGoogle Scholar
• 35  Xu W, Mimnaugh EG, Kim JS, Trepel JB, Neckers LM: Hsp90, not Grp94, regulates the intracellular trafficking and stability of nascent ErbB2. Cell Stress Chaperones7,91–96 (2002).
  Medline CASGoogle Scholar
• 36  Shimamura T, Lowell AM, Engelman JA, Shapiro GI: Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins. Cancer Res.65,6401–6408 (2005).
  Medline CASGoogle Scholar
• 37  Xu W, Soga S, Beebe K et al.: Sensitivity of epidermal growth factor receptor and ErbB2 exon 20 insertion mutants to Hsp90 inhibition. Br. J. Cancer97,741–744 (2007).
  Medline CASGoogle Scholar
• 38  Xu W, Yuan X, Xiang Z, Mimnaugh E, Marcu M, Neckers L: Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex. Nat. Struct. Mol. Biol.12,120–126 (2005).▪ Identifies the motif in the ErbB2 kinase domain that determines Hsp90 binding and geldanamycin sensitivity.
  Medline CASGoogle Scholar
• 39  Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF: Met, metastasis, motility and more. Nat. Rev. Mol. Cell Biol.4,915–925 (2003).
  Medline CASGoogle Scholar
• 40  Maulik G, Kijima T, Ma PC et al.: Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer. Clin. Cancer Res.8,620–627 (2002).
  Medline CASGoogle Scholar
• 41  Webb CP, Hose CD, Koochekpour S et al.: The geldanamycins are potent inhibitors of the hepatocyte growth factor/scatter factor-met-urokinase plasminogen activator-plasmin proteolytic network. Cancer Res.60,342–349 (2000).
  Medline CASGoogle Scholar
• 42  Zhang H, Yee D: The therapeutic potential of agents targeting the type I insulin-like growth factor receptor. Expert Opin. Investig. Drugs13,1569–1577 (2004).
  Medline CASGoogle Scholar
• 43  Yuen JS, Cockman ME, Sullivan M et al.: The VHL tumor suppressor inhibits expression of the IGF1R and its loss induces IGF1R upregulation in human clear cell renal carcinoma. Oncogene26,6499–6508 (2007).
  Medline CASGoogle Scholar
• 44  Nielsen TO, Andrews HN, Cheang M et al.: Expression of the insulin-like growth factor I receptor and urokinase plasminogen activator in breast cancer is associated with poor survival: potential for intervention with 17-allylamino geldanamycin. Cancer Res.64,286–291 (2004).
  Medline CASGoogle Scholar
• 45  Klinakis A, Szabolcs M, Chen G, Xuan S, Hibshoosh H, Efstratiadis A: Igf1r as a therapeutic target in a mouse model of basal-like breast cancer. Proc. Natl Acad. Sci. USA106,2359–2364 (2009).
  Medline CASGoogle Scholar
• 46  Bagatell R, Beliakoff J, David CL, Marron MT, Whitesell L: Hsp90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin. Int. J. Cancer113,179–188 (2005).
  Medline CASGoogle Scholar
• 47  Lang SA, Moser C, Gaumann A et al.: Targeting heat shock protein 90 in pancreatic cancer impairs insulin-like growth factor-I receptor signaling, disrupts an interleukin-6/signal-transducer and activator of transcription 3/hypoxia-inducible factor-1α autocrine loop, and reduces orthotopic tumor growth. Clin. Cancer Res.13,6459–6468 (2007).
  Medline CASGoogle Scholar
• 48  Carpenter G: Receptor tyrosine kinase substrates: src homology domains and signal transduction. FASEB J.6,3283–3289 (1992).
  Medline CASGoogle Scholar
• 49  Ishizawar R, Parsons SJ: c-Src and cooperating partners in human cancer. Cancer Cell6,209–214 (2004).
  Medline CASGoogle Scholar
• 50  Xu Y, Singer MA, 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. USA96,109–114 (1999).
  Medline CASGoogle Scholar
• 51  Bijlmakers MJ, Marsh M: Hsp90 is essential for the synthesis and subsequent membrane association, but not the maintenance, of the Src-kinase p56(lck). Mol. Biol. Cell11,1585–1595 (2000).
  Medline CASGoogle Scholar
• 52  Koga F, Xu W, Karpova TS et al.: Hsp90 inhibition transiently activates Src kinase and promotes Src-dependent Akt and Erk activation. Proc. Natl Acad. Sci. USA103,11318–11322 (2006).
  Medline CASGoogle Scholar
• 53  Xu W, Yuan X, Beebe K, Xiang Z, Neckers L: Loss of Hsp90 association up-regulates Src-dependent ErbB2 activity. Mol. Cell Biol.27,220–228 (2007).
  Medline CASGoogle Scholar
• 54  Price JT, Quinn JM, Sims NA et al.: The heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line. Cancer Res.65,4929–4938 (2005).▪▪ Initial description of Hsp90 inhibitor enhancement of bone metastasis in mice.
  Medline CASGoogle Scholar
• 55  Yano A, Tsutsumi S, Soga S et al.: Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone. Proc. Natl Acad. Sci. USA105,15541–15546 (2008).
  Medline CASGoogle Scholar
• 56  Samuels Y, Ericson K: Oncogenic PI3K and its role in cancer. Curr. Opin. Oncol.18,77–82 (2006).
  Medline CASGoogle Scholar
• 57  Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB: Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat. Rev. Drug Discov.4,988–1004 (2005).
  Medline CASGoogle Scholar
• 58  Qiao M, Sheng S, Pardee AB: Metastasis and AKT activation. Cell Cycle7,2991–2996 (2008).
  Medline CASGoogle Scholar
• 59  Fujita N, Sato S, Ishida A, Tsuruo T: Involvement of Hsp90 in signaling and stability of 3-phosphoinositide-dependent kinase-1. J. Biol. Chem.277,10346–10353 (2002).
  Medline CASGoogle Scholar
• 60  Sato S, Fujita N, Tsuruo T: Modulation of Akt kinase activity by binding to Hsp90. Proc. Natl Acad. Sci. USA97,10832–10837 (2000).
  Medline CASGoogle Scholar
• 61  Nimmanapalli R, O’Bryan E, Bhalla K: Geldanamycin and its analogue 17-allylamino-17-demethoxygeldanamycin lowers Bcr–Abl levels and induces apoptosis and differentiation of Bcr–Abl-positive human leukemic blasts. Cancer Res.61,1799–1804 (2001).
  Medline CASGoogle Scholar
• 62  Solit DB, Basso AD, Olshen AB, Scher HI, Rosen N: Inhibition of heat shock protein 90 function down-regulates Akt kinase and sensitizes tumors to Taxol. Cancer Res.63,2139–2144 (2003).
  Medline CASGoogle Scholar
• 63  Etienne-Manneville S, Hall A: Rho GTPases in cell biology. Nature420,629–635 (2002).
  Medline CASGoogle Scholar
• 64  Tu S, Wu WJ, Wang J, Cerione RA: Epidermal growth factor-dependent regulation of Cdc42 is mediated by the Src tyrosine kinase. J. Biol. Chem.278,49293–49300 (2003).
  Medline CASGoogle Scholar
• 65  Higuchi M, Masuyama N, Fukui Y, Suzuki A, Gotoh Y: Akt mediates Rac/Cdc42-regulated cell motility in growth factor-stimulated cells and in invasive PTEN knockout cells. Curr. Biol.11,1958–1962 (2001).
  Medline CASGoogle Scholar
• 66  Wymann MP, Marone R: Phosphoinositide 3-kinase in disease: timing, location, and scaffolding. Curr. Opin. Cell Biol.17,141–149 (2005).
  Medline CASGoogle Scholar
• 67  Modzelewska K, Newman LP, Desai R, Keely PJ: Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. J. Biol. Chem.281,37527–37535 (2006).
  Medline CASGoogle Scholar
• 68  Yang W, Jansen JM, Lin Q, Canova S, Cerione RA, Childress C: Interaction of activated Cdc42-associated tyrosine kinase ACK2 with HSP90. Biochem. J.382,199–204 (2004).
  Medline CASGoogle Scholar
• 69  Mahajan NP, Whang YE, Mohler JL, Earp HS: Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer Res.65,10514–10523 (2005).
  Medline CASGoogle Scholar
• 70  Minn AJ, Gupta GP, Siegel PM et al.: Genes that mediate breast cancer metastasis to lung. Nature436,518–524 (2005).
  Medline CASGoogle Scholar
• 71  Mook OR, Frederiks WM, Van Noorden CJ: The role of gelatinases in colorectal cancer progression and metastasis. Biochim. Biophys. Acta1705,69–89 (2004).
  Medline CASGoogle Scholar
• 72  Wang Y: The role and regulation of urokinase-type plasminogen activator receptor gene expression in cancer invasion and metastasis. Med. Res. Rev.21,146–170 (2001).
  MedlineGoogle Scholar
• 73  Kim MS, Kwak HJ, Lee JW et al.: 17-Allylamino-17-demethoxygeldanamycin down-regulates hyaluronic acid-induced glioma invasion by blocking matrix metalloproteinase-9 secretion. Mol. Cancer Res.6,1657–1665 (2008).
  Medline CASGoogle Scholar
• 74  Saaristo A, Karpanen T, Alitalo K: Mechanisms of angiogenesis and their use in the inhibition of tumor growth and metastasis. Oncogene19,6122–6129 (2000).
  Medline CASGoogle Scholar
• 75  Rankin EB, Giaccia AJ: The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ.15,678–685 (2008).
  Medline CASGoogle Scholar
• 76  Bratslavsky G, Sudarshan S, Neckers L, Linehan WM: Pseudohypoxic pathways in renal cell carcinoma. Clin. Cancer Res.13,4667–4671 (2007).
  Medline CASGoogle Scholar
• 77  Isaacs JS, Jung YJ, Neckers L: Aryl hydrocarbon nuclear translocator (ARNT) promotes oxygen-independent stabilization of hypoxia-inducible factor-1α by modulating an Hsp90-dependent regulatory pathway. J. Biol. Chem.279,16128–16135 (2004).
  Medline CASGoogle Scholar
• 78  Mabjeesh NJ, Post DE, Willard MT et al.: Geldanamycin induces degradation of hypoxia-inducible factor 1α protein via the proteosome pathway in prostate cancer cells. Cancer Res.62,2478–2482 (2002).
  Medline CASGoogle Scholar
• 79  Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM: Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 α-degradative pathway. J. Biol. Chem.277,29936–29944 (2002).
  Medline CASGoogle Scholar
• 80  Karkkainen MJ, Petrova TV: Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene19,5598–5605 (2000).
  Medline CASGoogle Scholar
• 81  Le Boeuf F, Houle F, Huot J: Regulation of vascular endothelial growth factor receptor 2-mediated phosphorylation of focal adhesion kinase by heat shock protein 90 and Src kinase activities. J. Biol. Chem.279,39175–39185 (2004).
  MedlineGoogle Scholar
• 82  Kaur G, Belotti D, Burger AM et al.: Antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: an orally bioavailable heat shock protein 90 modulator. Clin. Cancer Res.10,4813–4821 (2004).
  Medline CASGoogle Scholar
• 83  Sanderson S, Valenti M, Gowan S et al.: Benzoquinone ansamycin heat shock protein 90 inhibitors modulate multiple functions required for tumor angiogenesis. Mol. Cancer Ther.5,522–532 (2006).
  Medline CASGoogle Scholar
• 84  Yu J, Ustach C, Kim HR: Platelet-derived growth factor signaling and human cancer. J. Biochem. Mol. Biol.36,49–59 (2003).
  Medline CASGoogle Scholar
• 85  Andrae J, Gallini R, Betsholtz C: Role of platelet-derived growth factors in physiology and medicine. Genes Dev.22,1276–1312 (2008).
  Medline CASGoogle Scholar
• 86  Matei D, Satpathy M, Cao L, Lai YC, Nakshatri H, Donner DB: The platelet-derived growth factor receptor α is destabilized by geldanamycins in cancer cells. J. Biol. Chem.282,445–453 (2007).
  Medline CASGoogle Scholar
• 87  Tsutsumi S, Neckers L: Extracellular heat shock protein 90: a role for a molecular chaperone in cell motility and cancer metastasis. Cancer Sci.98,1536–1539 (2007).
  Medline CASGoogle Scholar
• 88  Becker B, Multhoff G, Farkas B et al.: Induction of Hsp90 protein expression in malignant melanomas and melanoma metastases. Exp. Dermatol.13,27–32 (2004).
  Medline CASGoogle Scholar
• 89  Cheng CF, Fan J, Fedesco M et al.: Transforming growth factor a (TGFα)-stimulated secretion of HSP90α: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFβ-rich environment during wound healing. Mol. Cell Biol.28,3344–3358 (2008).
  Medline CASGoogle Scholar
• 90  Li W, Li Y, Guan S et al.: Extracellular heat shock protein-90α: linking hypoxia to skin cell motility and wound healing. EMBO J.26,1221–1233 (2007).
  Medline CASGoogle Scholar
• 91  Yang Y, Rao R, Shen J et al.: Role of acetylation and extracellular location of heat shock protein 90α in tumor cell invasion. Cancer Res.68,4833–4842 (2008).
  Medline CASGoogle Scholar
• 92  Lei H, Venkatakrishnan A, Yu S, Kazlauskas A: Protein kinase A-dependent translocation of Hsp90 α impairs endothelial nitric-oxide synthase activity in high glucose and diabetes. J. Biol. Chem.282,9364–9371 (2007).
  Medline CASGoogle Scholar
• 93  Nickel W: Unconventional secretory routes: direct protein export across the plasma membrane of mammalian cells. Traffic6,607–614 (2005).
  Medline CASGoogle Scholar
• 94  Clayton A, Turkes A, Navabi H, Mason MD, Tabi Z: Induction of heat shock proteins in B-cell exosomes. J. Cell Sci.118,3631–3638 (2005).
  Medline CASGoogle Scholar
• 95  Eustace BK, Sakurai T, Stewart JK et al.: Functional proteomic screens reveal an essential extracellular role for hsp90 α in cancer cell invasiveness. Nat. Cell Biol.6,507–514 (2004).▪ First report to show a role of extracellular Hsp90 in cancer cell invasion.
  Medline CASGoogle Scholar
• 96  Sidera K, Samiotaki M, Yfanti E, Panayotou G, Patsavoudi E: Involvement of cell surface HSP90 in cell migration reveals a novel role in the developing nervous system. J. Biol. Chem.279,45379–45388 (2004).
  Medline CASGoogle Scholar
• 97  Tsutsumi S, Scroggins B, Koga F et al.: A small molecule cell-impermeant Hsp90 antagonist inhibits tumor cell motility and invasion. Oncogene27,2478–2487 (2008).
  Medline CASGoogle Scholar
• 98  Stellas D, Karameris A, Patsavoudi E: Monoclonal antibody 4C5 immunostains human melanomas and inhibits melanoma cell invasion and metastasis. Clin. Cancer Res.13,1831–1838 (2007).
  Medline CASGoogle Scholar
• 99  Sidera K, Gaitanou M, Stellas D, Matsas R, Patsavoudi E: A critical role for HSP90 in cancer cell invasion involves interaction with the extracellular domain of HER-2. J. Biol. Chem.283,2031–2041 (2008).
  Medline CASGoogle Scholar
• 100  Chiosis G, Rodina A, Moulick K: Emerging Hsp90 inhibitors: from discovery to clinic. Anticancer Agents Med. Chem.6,1–8 (2006).
  Medline CASGoogle Scholar
• 101  Barluenga S, Wang C, Fontaine JG et al.: Divergent synthesis of a pochonin library targeting HSP90 and in vivo efficacy of an identified inhibitor. Angew. Chem. Int. Ed. Engl.47,4432–4435 (2008).
  Medline CASGoogle Scholar
• 102  Okawa Y, Hideshima T, Steed P et al.: SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood113,846–855 (2009).
  Medline CASGoogle Scholar
• 103  Messaoudi S, Peyrat JF, Brion JD, Alami M: Recent advances in Hsp90 inhibitors as antitumor agents. Anticancer Agents Med. Chem.8,761–782 (2008).
  Medline CASGoogle Scholar
• 104  Gyurkocza B, Plescia J, Raskett CM et al.: Antileukemic activity of shepherdin and molecular diversity of hsp90 inhibitors. J. Natl Cancer Inst.98,1068–1077 (2006).
  Medline CASGoogle Scholar
• 105  Mitsiades CS, Mitsiades NS, McMullan CJ et al.: Antimyeloma activity of heat shock protein-90 inhibition. Blood107,1092–1100 (2006).
  Medline CASGoogle Scholar
• 106  Modi S, Stopeck AT, Gordon MS et al.: Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a Phase I dose-escalation study. J. Clin. Oncol.25,5410–5417 (2007).
  Medline CASGoogle Scholar
• 201  World Health Organization www.who.int/en
  Google Scholar