Cancer Treatment Reviews
Volume 36, Issue 4 , Pages 318-327 , June 2010

Targets for cancer therapy in childhood sarcomas

References 

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA: Cancer J Clin. 2007;57:43–66
  2. Linabery AM, Ross JA. Childhood and adolescent cancer survival in the US by race and ethnicity for the diagnostic period 1975–1999. Cancer. 2008;113:2575–2596
  3. Landier W, Bhatia S. Cancer survivorship: a pediatric perspective. Oncologist 2008.
  4. Benson JD, Chen YN, Cornell-Kennon SA, et al. Validating cancer drug targets. Nature. 2006;441:451–456
  5. Weinstein IB, Joe A. Oncogene addiction. Cancer Res. 2008;68:3077–3080
  6. Baselga J, Arribas J. Treating cancer’s kinase ‘addiction’. Nat Med. 2004;10:786–787
  7. van der Geer P, Hunter T, Lindberg RA. Receptor protein – tyrosine kinases and their signal transduction pathways. Ann Rev Cell Biol. 1994;10:251–337
  8. Helman LJ, Meltzer P. Mechanisms of sarcoma development. Nat Rev Cancer. 2003;3:685–694
  9. Sachdev D, Yee D. Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther. 2007;6:1–12
  10. Scotlandi K, Picci P. Targeting insulin-like growth factor 1 receptor in sarcomas. Curr Opin Oncol. 2008;20:419–427
  11. Martins AS, Mackintosh C, Martin DH, et al. Insulin-like growth factor I receptor pathway inhibition by ADW742, alone or in combination with imatinib, doxorubicin, or vincristine, is a novel therapeutic approach in Ewing tumor. Clin Cancer Res. 2006;12:3532–3540
  12. Scotlandi K, Avnet S, Benini S, et al. Expression of an IGF-I receptor dominant negative mutant induces apoptosis, inhibits tumorigenesis and enhances chemosensitivity in Ewing’s sarcoma cells. Int J Cancer. 2002;101:11–16
  13. Scotlandi K, Benini S, Nanni P, et al. Blockage of insulin-like growth factor-I receptor inhibits the growth of Ewing’s sarcoma in athymic mice. Cancer Res. 1998;58:4127–4131
  14. Kalebic T, Tsokos M, Helman LJ. In vivo treatment with antibody against IGF-1 receptor suppresses growth of human rhabdomyosarcoma and down-regulates p34cdc2. Cancer Res. 1994;54:5531–5534
  15. Kalebic T, Blakesley V, Slade C, Plasschaert S, Leroith D, Helman LJ. Expression of a kinase-deficient IGF-I-R suppresses tumorigenicity of rhabdomyosarcoma cells constitutively expressing a wild type IGF-I-R. Int J Cancer. 1998;76:223–227
  16. Manara MC, Landuzzi L, Nanni P, et al. Preclinical in vivo study of new insulin-like growth factor-I receptor-specific inhibitor in Ewing’s sarcoma. Clin Cancer Res. 2007;13:1322–1330
  17. Scotlandi K, Maini C, Manara MC, et al. Effectiveness of insulin-like growth factor I receptor antisense strategy against Ewing’s sarcoma cells. Cancer Gene Ther. 2002;9:296–307
  18. Maloney EK, McLaughlin JL, Dagdigian NE, et al. An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Cancer Res. 2003;63:5073–5083
  19. Kolb EA, Gorlick R, Houghton PJ, et al. Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;50:1190–1197
  20. Scotlandi K, Manara MC, Nicoletti G, et al. Antitumor activity of the insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 in musculoskeletal tumors. Cancer Res. 2005;65:3868–3876
  21. Cao L, Yu Y, Darko I, et al. Addiction to elevated insulin-like growth factor i receptor and initial modulation of the AKT pathway define the responsiveness of rhabdomyosarcoma to the targeting antibody. Cancer Res. 2008;68:8039–8048
  22. Naka T, Iwamoto Y, Shinohara N, Ushijima M, Chuman H, Tsuneyoshi M. Expression of c-met proto-oncogene product (c-MET) in benign and malignant bone tumors. Mod Pathol. 1997;10:832–838
  23. Patane S, Avnet S, Coltella N, et al. MET overexpression turns human primary osteoblasts into osteosarcomas. Cancer Res. 2006;66:4750–4757
  24. Scotlandi K, Baldini N, Oliviero M, et al. Expression of met/hepatocyte growth factor receptor gene and malignant behavior of musculoskeletal tumors. Am J Pathol. 1996;149:1209–1219
  25. Coltella N, Manara MC, Cerisano V, et al. Role of the MET/HGF receptor in proliferation and invasive behavior of osteosarcoma. FASEB J. 2003;17:1162–1164
  26. MacEwen EG, Kutzke J, Carew J, et al. C-Met tyrosine kinase receptor expression and function in human and canine osteosarcoma cells. Clin Exp Metastasis. 2003;20:421–430
  27. Ferracini R, Olivero M, Di Renzo MF, et al. Retrogenic expression of the MET proto-oncogene correlates with the invasive phenotype of human rhabdomyosarcomas. Oncogene. 1996;12:1697–1705
  28. Jankowski K, Kucia M, Wysoczynski M, et al. Both hepatocyte growth factor (HGF) and stromal-derived factor-1 regulate the metastatic behavior of human rhabdomyosarcoma cells, but only HGF enhances their resistance to radiochemotherapy. Cancer Res. 2003;63:7926–7935
  29. Rees H, Williamson D, Papanastasiou A, et al. The MET receptor tyrosine kinase contributes to invasive tumour growth in rhabdomyosarcomas. Growth Factors (Chur, Switzerland). 2006;24:197–208
  30. Sharp R, Recio JA, Jhappan C, et al. Synergism between INK4a/ARF inactivation and aberrant HGF/SF signaling in rhabdomyosarcomagenesis. Nat Med. 2002;8:1276–1280
  31. Taulli R, Scuoppo C, Bersani F, et al. Validation of met as a therapeutic target in alveolar and embryonal rhabdomyosarcoma. Cancer Res. 2006;66:4742–4749
  32. Migliore C, Giordano S. Molecular cancer therapy: can our expectation be MET?. Eur J Cancer. 2008;44:641–651
  33. Armistead PM, Salganick J, Roh JS, et al. Expression of receptor tyrosine kinases and apoptotic molecules in rhabdomyosarcoma: correlation with overall survival in 105 patients. Cancer. 2007;110:2293–2303
  34. Kubo T, Piperdi S, Rosenblum J, et al. Platelet-derived growth factor receptor as a prognostic marker and a therapeutic target for imatinib mesylate therapy in osteosarcoma. Cancer. 2008;112:2119–2129
  35. Sulzbacher I, Traxler M, Mosberger I, Lang S, Chott A. Platelet-derived growth factor-AA and -alpha receptor expression suggests an autocrine and/or paracrine loop in osteosarcoma. Mod Pathol. 2000;13:632–637
  36. Scotlandi K, Manara MC, Strammiello R, et al. C-kit receptor expression in Ewing’s sarcoma: lack of prognostic value but therapeutic targeting opportunities in appropriate conditions. J Clin Oncol. 2003;21:1952–1960
  37. Bozzi F, Tamborini E, Negri T, et al. Evidence for activation of KIT, PDGFRalpha, and PDGFRbeta receptors in the Ewing sarcoma family of tumors. Cancer. 2007;109:1638–1645
  38. Smithey BE, Pappo AS, Hill DA. C-kit expression in pediatric solid tumors: a comparative immunohistochemical study. Am J Surg Pathol. 2002;26:486–492
  39. Do I, Araujo ES, Kalil RK, et al. Protein expression of KIT and gene mutation of c-kit and PDGFRs in Ewing sarcomas. Pathol Res Pract. 2007;203:127–134
  40. McDowell HP, Meco D, Riccardi A, et al. Imatinib mesylate potentiates topotecan antitumor activity in rhabdomyosarcoma preclinical models. Int J Cancer. 2007;120:1141–1149
  41. McGary EC, Weber K, Mills L, et al. Inhibition of platelet-derived growth factor-mediated proliferation of osteosarcoma cells by the novel tyrosine kinase inhibitor STI571. Clin Cancer Res. 2002;8:3584–3591
  42. Sulzbacher I, Birner P, Trieb K, Traxler M, Lang S, Chott A. Expression of platelet-derived growth factor-AA is associated with tumor progression in osteosarcoma. Mod Pathol. 2003;16:66–71
  43. Gonzalez I, Andreu EJ, Panizo A, et al. Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis. Clin Cancer Res. 2004;10:751–761
  44. Merchant MS, Woo CW, Mackall CL, Thiele CJ. Potential use of imatinib in Ewing’s sarcoma: evidence for in vitro and in vivo activity. J Natl Cancer Inst. 2002;94:1673–1679
  45. Taniguchi E, Nishijo K, McCleish AT, et al. PDGFR-A is a therapeutic target in alveolar rhabdomyosarcoma. Oncogene. 2008;27:6550–6560
  46. Beppu K, Jaboine J, Merchant MS, Mackall CL, Thiele CJ. Effect of imatinib mesylate on neuroblastoma tumorigenesis and vascular endothelial growth factor expression. J Natl Cancer Inst. 2004;96:46–55
  47. Maris JM, Courtright J, Houghton PJ, et al. Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;51:42–48
  48. Bond M, Bernstein ML, Pappo A, et al. A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: a Children’s Oncology Group study. Pediatr Blood Cancer. 2008;50:254–258
  49. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489–501
  50. Crabbe T, Welham MJ, Ward SG. The PI3K inhibitor arsenal: choose your weapon!. Trends Biochem Sci. 2007;32:450–456
  51. Trotman LC, Pandolfi PP. PTEN and p53: who will get the upper hand?. Cancer Cell. 2003;3:97–99
  52. Workman P, Clarke PA, Guillard S, Raynaud FI. Drugging the PI3 kinome. Nat Biotechnol. 2006;24:794–796
  53. Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS, Workman P. Targeting the PI3K–AKT–mTOR pathway: progress, pitfalls, and promises. Curr Opin Pharmacol. 2008;8:393–412
  54. Mateo-Lozano S, Tirado OM, Notario V. Rapamycin induces the fusion-type independent downregulation of the EWS/FLI-1 proteins and inhibits Ewing’s sarcoma cell proliferation. Oncogene. 2003;22:9282–9287
  55. Gordon IK, Ye F, Kent MS. Evaluation of the mammalian target of rapamycin pathway and the effect of rapamycin on target expression and cellular proliferation in osteosarcoma cells from dogs. Am J Vet Res. 2008;69:1079–1084
  56. Petricoin EF, Espina V, Araujo RP, et al. Phosphoprotein pathway mapping: Akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival. Cancer Res. 2007;67:3431–3440
  57. Hosoi H, Dilling MB, Shikata T, et al. Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells. Cancer Res. 1999;59:886–894
  58. Houghton PJ, Morton CL, Kolb EA, et al. Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;50:799–805
  59. Wan X, Shen N, Mendoza A, Khanna C, Helman LJ. CCI-779 inhibits rhabdomyosarcoma xenograft growth by an antiangiogenic mechanism linked to the targeting of mTOR/Hif-1alpha/VEGF signaling. Neoplasia. 2006;8:394–401
  60. Huang S, Shu L, Dilling MB, et al. Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1). Mol Cell. 2003;11:1491–1501
  61. Kurmasheva RT, Harwood FC, Houghton PJ. Differential regulation of vascular endothelial growth factor by Akt and mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors. Mol Cancer Ther. 2007;6:1620–1628
  62. Guba M, von Breitenbuch P, Steinbauer M, et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med. 2002;8:128–135
  63. Fouladi M, Laningham F, Wu J, et al. Phase I study of everolimus in pediatric patients with refractory solid tumors. J Clin Oncol. 2007;25:4806–4812
  64. Wan X, Harkavy B, Shen N, Grohar P, Helman LJ. Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism. Oncogene. 2007;26:1932–1940
  65. Thimmaiah KN, Easton J, Huang S, et al. Insulin-like growth factor I-mediated protection from rapamycin-induced apoptosis is independent of Ras–Erk1–Erk2 and phosphatidylinositol 3′-kinase-Akt signaling pathways. Cancer Res. 2003;63:364–374
  66. Malumbres M, Barbacid M. To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer. 2001;1:222–231
  67. Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 2006;24:1770–1783
  68. Baer C, Nees M, Breit S, et al. Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing’s sarcoma. Int J Cancer. 2004;110:687–694
  69. Zhang J, Hu S, Schofield DE, Sorensen PH, Triche TJ. Selective usage of D-type cyclins by Ewing’s tumors and rhabdomyosarcomas. Cancer Res. 2004;64:6026–6034
  70. Ohali A, Avigad S, Zaizov R, et al. Prediction of high risk Ewing’s sarcoma by gene expression profiling. Oncogene. 2004;23:8997–9006
  71. Kovar H, Jug G, Aryee DN, et al. Among genes involved in the RB dependent cell cycle regulatory cascade, the p16 tumor suppressor gene is frequently lost in the Ewing family of tumors. Oncogene. 1997;15:2225–2232
  72. Dauphinot L, De Oliveira C, Melot T, et al. Analysis of the expression of cell cycle regulators in Ewing cell lines: EWS-FLI-1 modulates p57KIP2and c-Myc expression. Oncogene. 2001;20:3258–3265
  73. Iolascon A, Faienza MF, Coppola B, et al. Analysis of cyclin-dependent kinase inhibitor genes (CDKN2A, CDKN2B, and CDKN2C) in childhood rhabdomyosarcoma. Genes Chromosomes Cancer. 1996;15:217–222
  74. Maelandsmo GM, Berner JM, Florenes VA, et al. Homozygous deletion frequency and expression levels of the CDKN2 gene in human sarcomas – relationship to amplification and mRNA levels of CDK4 and CCND1. Br J Cancer. 1995;72:393–398
  75. Obana K, Yang HW, Piao HY, et al. Aberrations of p16INK4A, p14ARF and p15INK4B genes in pediatric solid tumors. Int J Oncol. 2003;23:1151–1157
  76. Roeb W, Boyer A, Cavenee WK, Arden KC. PAX3-FOXO1 controls expression of the p57Kip2 cell-cycle regulator through degradation of EGR1. Proc Natl Acad Sci USA. 2007;104:18085–18090
  77. Miller CW, Aslo A, Campbell MJ, Kawamata N, Lampkin BC, Koeffler HP. Alterations of the p15, p16, and p18 genes in osteosarcoma. Cancer Genet Cytogenet. 1996;86:136–142
  78. Li Y, Tanaka K, Li X, et al. Cyclin-dependent kinase inhibitor, flavopiridol, induces apoptosis and inhibits tumor growth in drug-resistant osteosarcoma and Ewing’s family tumor cells. Int J Cancer. 2007;121:1212–1218
  79. Li X, Tanaka K, Nakatani F, et al. Transactivation of cyclin E gene by EWS-Fli1 and antitumor effects of cyclin dependent kinase inhibitor on Ewing’s family tumor cells. Int J Cancer. 2005;116:385–394
  80. Tirado OM, Mateo-Lozano S, Notario V. Roscovitine is an effective inducer of apoptosis of Ewing’s sarcoma family tumor cells in vitro and in vivo. Cancer Res. 2005;65:9320–9327
  81. Bettayeb K, Tirado OM, Marionneau-Lambot S, et al. Meriolins, a new class of cell death inducing kinase inhibitors with enhanced selectivity for cyclin-dependent kinases. Cancer Res. 2007;67:8325–8334
  82. Saab R, Bills JL, Miceli AP, et al. Pharmacologic inhibition of cyclin-dependent kinase 4/6 activity arrests proliferation in myoblasts and rhabdomyosarcoma-derived cells. Mol Cancer Ther. 2006;5:1299–1308
  83. Boerner SA, Tourne ME, Kaufmann SH, Bible KC. Effect of P-glycoprotein on flavopiridol sensitivity. Br J Cancer. 2001;84:1391–1396
  84. Whitlock JA, Krailo M, Reid JM, et al. Phase I clinical and pharmacokinetic study of flavopiridol in children with refractory solid tumors: a Children’s Oncology Group Study. J Clin Oncol. 2005;23:9179–9186
  85. Morris DG, Bramwell VH, Turcotte R, et al. A phase II study of flavopiridol in patients with previously untreated advanced soft tissue sarcoma. Sarcoma. 2006;64374
  86. Ganjavi H, Gee M, Narendran A, Freedman MH, Malkin D. Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin. Cancer Gene Ther. 2005;12:397–406
  87. Ganjavi H, Gee M, Narendran A, et al. Adenovirus-mediated p53 gene therapy in osteosarcoma cell lines: sensitization to cisplatin and doxorubicin. Cancer Gene Ther. 2006;13:415–419
  88. Shetty S, Taylor AC, Harris LC. Selective chemosensitization of rhabdomyosarcoma cell lines following wild-type p53 adenoviral transduction. Anticancer Drugs. 2002;13:881–889
  89. Lock R, Carol H, Houghton PJ, et al. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;50:1181–1189
  90. Ashkenazi A, Pai RC, Fong S, et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999;104:155–162
  91. Wang S. The promise of cancer therapeutics targeting the TNF-related apoptosis-inducing ligand and TRAIL receptor pathway. Oncogene. 2008;27:6207–6215
  92. Walczak H, Degli-Esposti MA, Johnson RS, et al. TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J. 1997;16:5386–5397
  93. Petak I, Douglas L, Tillman DM, Vernes R, Houghton JA. Pediatric rhabdomyosarcoma cell lines are resistant to Fas-induced apoptosis and highly sensitive to TRAIL-induced apoptosis. Clin Cancer Res. 2000;6:4119–4127
  94. Kontny HU, Hammerle K, Klein R, Shayan P, Mackall CL, Niemeyer CM. Sensitivity of Ewing’s sarcoma to TRAIL-induced apoptosis. Cell Death Differ. 2001;8:506–514
  95. Van Valen F, Fulda S, Truckenbrod B, et al. Apoptotic responsiveness of the Ewing’s sarcoma family of tumours to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Int J Cancer. 2000;88:252–259
  96. Kumar A, Jasmin A, Eby MT, Chaudhary PM. Cytotoxicity of Tumor necrosis factor related apoptosis-inducing ligand towards Ewing’s sarcoma cell lines. Oncogene. 2001;20:1010–1014
  97. Mitsiades N, Poulaki V, Mitsiades C, Tsokos M. Ewing’s sarcoma family tumors are sensitive to tumor necrosis factor-related apoptosis-inducing ligand and express death receptor 4 and death receptor 5. Cancer Res. 2001;61:2704–2712
  98. Hotta T, Suzuki H, Nagai S, et al. Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand-induced caspase-8 activation, apoptosis and loss of mitochondrial membrane potential. J Orthop Res. 2003;21:949–957
  99. Mirandola P, Sponzilli I, Gobbi G, et al. Anticancer agents sensitize osteosarcoma cells to TNF-related apoptosis-inducing ligand downmodulating IAP family proteins. Int J Oncol. 2006;28:127–133
  100. Evdokiou A, Bouralexis S, Atkins GJ, et al. Chemotherapeutic agents sensitize osteogenic sarcoma cells, but not normal human bone cells, to Apo2L/TRAIL-induced apoptosis. Int J Cancer. 2002;99:491–504
  101. Lissat A, Vraetz T, Tsokos M, et al. Interferon-gamma sensitizes resistant Ewing’s sarcoma cells to tumor necrosis factor apoptosis-inducing ligand-induced apoptosis by up-regulation of caspase-8 without altering chemosensitivity. Am J Pathol. 2007;170:1917–1930
  102. Komdeur R, Meijer C, Van Zweeden M, et al. Doxorubicin potentiates TRAIL cytotoxicity and apoptosis and can overcome TRAIL-resistance in rhabdomyosarcoma cells. Int J Oncol. 2004;25:677–684
  103. Tomek S, Koestler W, Horak P, et al. Trail-induced apoptosis and interaction with cytotoxic agents in soft tissue sarcoma cell lines. Eur J Cancer. 2003;39:1318–1329
  104. Clayer M, Bouralexis S, Evdokiou A, Hay S, Atkins GJ, Findlay DM. Enhanced apoptosis of soft tissue sarcoma cells with chemotherapy: a potential new approach using TRAIL. J Orthop Surg (Hong Kong). 2001;9:19–22
  105. Izeradjene K, Douglas L, Delaney A, Houghton JA. Influence of casein kinase II in tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human rhabdomyosarcoma cells. Clin Cancer Res. 2004;10:6650–6660
  106. Locklin RM, Federici E, Espina B, Hulley PA, Russell RG, Edwards CM. Selective targeting of death receptor 5 circumvents resistance of MG-63 osteosarcoma cells to TRAIL-induced apoptosis. Mol Cancer Ther. 2007;6:3219–3228
  107. Montagut C, Rovira A, Albanell J. The proteasome: a novel target for anticancer therapy. Clin Transl Oncol. 2006;8:313–317
  108. Bersani F, Taulli R, Accornero P, et al. Bortezomib-mediated proteasome inhibition as a potential strategy for the treatment of rhabdomyosarcoma. Eur J Cancer. 2008;44:876–884
  109. Lu G, Punj V, Chaudhary PM. Proteasome inhibitor Bortezomib induces cell cycle arrest and apoptosis in cell lines derived from Ewing’s sarcoma family of tumors and synergizes with TRAIL. Cancer Biol Ther. 2008;7:603–608
  110. Lauricella M, D’Anneo A, Giuliano M, et al. Induction of apoptosis in human osteosarcoma Saos-2 cells by the proteasome inhibitor MG132 and the protective effect of pRb. Cell Death Differ. 2003;10:930–932
  111. Yan XB, Yang DS, Gao X, Feng J, Shi ZL, Ye Z. Caspase-8 dependent osteosarcoma cell apoptosis induced by proteasome inhibitor MG132. Cell Biol Int. 2007;31:1136–1143
  112. Houghton PJ, Morton CL, Kolb EA, et al. Initial testing (stage 1) of the proteasome inhibitor bortezomib by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;50:37–45
  113. Maki RG, Kraft AS, Scheu K, et al. A multicenter phase II study of bortezomib in recurrent or metastatic sarcomas. Cancer. 2005;103:1431–1438
  114. Cullinan SB, Whitesell L. Heat shock protein 90: a unique chemotherapeutic target. Semin Oncol. 2006;33:457–465
  115. Lesko E, Gozdzik J, Kijowski J, Jenner B, Wiecha O, Majka M. HSP90 antagonist, geldanamycin, inhibits proliferation, induces apoptosis and blocks migration of rhabdomyosarcoma cells in vitro and seeding into bone marrow in vivo. Anticancer Drugs. 2007;18:1173–1181
  116. Smith MA, Morton CL, Phelps DA, et al. Stage 1 testing and pharmacodynamic evaluation of the HSP90 inhibitor alvespimycin (17-DMAG, KOS-1022) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;51:34–41
  117. Martins AS, Ordonez JL, Garcia-Sanchez A, et al. A pivotal role for heat shock protein 90 in Ewing sarcoma resistance to anti-insulin-like growth factor 1 receptor treatment: in vitro and in vivo study. Cancer Res. 2008;68:6260–6270
  118. 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 Cancer. 2005;113:179–188
  119. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev. 2006;5:769–784
  120. Kelly WK, Marks PA. Drug insight: histone deacetylase inhibitors – development of the new targeted anticancer agent suberoylanilide hydroxamic acid. Nat Clin Pract. 2005;2:150–157
  121. Karagiannis TC, El-Osta A. Clinical potential of histone deacetylase inhibitors as stand alone therapeutics and in combination with other chemotherapeutics or radiotherapy for cancer. Epigenetics. 2006;1:121–126
  122. Sakimura R, Tanaka K, Nakatani F, et al. Antitumor effects of histone deacetylase inhibitor on Ewing’s family tumors. Int J Cancer. 2005;116:784–792
  123. Nakatani F, Tanaka K, Sakimura R, et al. Identification of p21WAF1/CIP1 as a direct target of EWS-Fli1 oncogenic fusion protein. J Biol Chem. 2003;278:15105–15115
  124. Sonnemann J, Dreyer L, Hartwig M, et al. Histone deacetylase inhibitors induce cell death and enhance the apoptosis-inducing activity of TRAIL in Ewing’s sarcoma cells. J Cancer Res Clin Oncol. 2007;133:847–858
  125. Jaboin J, Wild J, Hamidi H, et al. MS-27-275, an inhibitor of histone deacetylase, has marked in vitro and in vivo antitumor activity against pediatric solid tumors. Cancer Res. 2002;62:6108–6115
  126. Imai T, Adachi S, Nishijo K, et al. FR901228 induces tumor regression associated with induction of Fas ligand and activation of Fas signaling in human osteosarcoma cells. Oncogene. 2003;22:9231–9242
  127. Roh MS, Kim CW, Park BS, et al. Mechanism of histone deacetylase inhibitor trichostatin A induced apoptosis in human osteosarcoma cells. Apoptosis. 2004;9:583–589
  128. Kutko MC, Glick RD, Butler LM, et al. Histone deacetylase inhibitors induce growth suppression and cell death in human rhabdomyosarcoma in vitro. Clin Cancer Res. 2003;9:5749–5755
  129. Yamanegi K, Yamane J, Hata M, et al. Sodium valproate, a histone deacetylase inhibitor, decreases the secretion of soluble Fas by human osteosarcoma cells and increases their sensitivity to Fas-mediated cell death. J Cancer Res Clin Oncol 2008.
  130. Watanabe K, Okamoto K, Yonehara S. Sensitization of osteosarcoma cells to death receptor-mediated apoptosis by HDAC inhibitors through downregulation of cellular FLIP. Cell Death Differ. 2005;12:10–18
  131. Hurtubise A, Bernstein ML, Momparler RL. Preclinical evaluation of the antineoplastic action of 5-aza-2′-deoxycytidine and different histone deacetylase inhibitors on human Ewing’s sarcoma cells. Cancer Cell Int. 2008;8:16
  132. Okada T, Tanaka K, Nakatani F, et al. Involvement of P-glycoprotein and MRP1 in resistance to cyclic tetrapeptide subfamily of histone deacetylase inhibitors in the drug-resistant osteosarcoma and Ewing’s sarcoma cells. Int J Cancer. 2006;118:90–97
  133. Folkman J. Angiogenesis. Ann Rev Med. 2006;57:1–18
  134. Balasubramanian L, Evens AM. Targeting angiogenesis for the treatment of sarcoma. Curr Opin Oncol. 2006;18:354–359
  135. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002;2:795–803
  136. Guan H, Zhou Z, Wang H, Jia SF, Liu W, Kleinerman ES. A small interfering RNA targeting vascular endothelial growth factor inhibits Ewing’s sarcoma growth in a xenograft mouse model. Clin Cancer Res. 2005;11:2662–2669
  137. Dalal S, Berry AM, Cullinane CJ, et al. Vascular endothelial growth factor: a therapeutic target for tumors of the Ewing’s sarcoma family. Clin Cancer Res. 2005;11:2364–2378
  138. Kaya M, Wada T, Akatsuka T, et al. Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res. 2000;6:572–577
  139. Kaya M, Wada T, Kawaguchi S, et al. Increased pre-therapeutic serum vascular endothelial growth factor in patients with early clinical relapse of osteosarcoma. Br J Cancer. 2002;86:864–869
  140. Maris JM, Courtright J, Houghton PJ, et al. Initial testing of the VEGFR inhibitor AZD2171 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;50:581–587
  141. Zhang L, Hannay JA, Liu J, et al. Vascular endothelial growth factor overexpression by soft tissue sarcoma cells: implications for tumor growth, metastasis, and chemoresistance. Cancer Res. 2006;66:8770–8778
  142. Yin D, Jia T, Gong W, et al. VEGF blockade decelerates the growth of a murine experimental osteosarcoma. Int J Oncol. 2008;33:253–259
  143. Park HR, Min K, Kim HS, Jung WW, Park YK. Expression of vascular endothelial growth factor-C and its receptor in osteosarcomas. Pathol Res Pract. 2008;204:575–582
  144. Gee MF, Tsuchida R, Eichler-Jonsson C, Das B, Baruchel S, Malkin D. Vascular endothelial growth factor acts in an autocrine manner in rhabdomyosarcoma cell lines and can be inhibited with all-trans-retinoic acid. Oncogene. 2005;24:8025–8037
  145. Onisto M, Slongo ML, Gregnanin L, Gastaldi T, Carli M, Rosolen A. Expression and activity of vascular endothelial growth factor and metalloproteinases in alveolar and embryonal rhabdomyosarcoma cell lines. Int J Oncol. 2005;27:791–798
  146. Bellamy WT, Richter L, Frutiger Y, Grogan TM. Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res. 1999;59:728–733
  147. Masood R, Cai J, Zheng T, Smith DL, Hinton DR, Gill PS. Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor-positive human tumors. Blood. 2001;98:1904–1913
  148. Wu Y, Zhong Z, Huber J, et al. Anti-vascular endothelial growth factor receptor-1 antagonist antibody as a therapeutic agent for cancer. Clin Cancer Res. 2006;12:6573–6584
  149. Glade Bender JL, Adamson PC, Reid JM, et al. Phase I trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors: a Children’s Oncology Group Study. J Clin Oncol. 2008;26:399–405
  150. Benesch M, Windelberg M, Sauseng W, et al. Compassionate use of bevacizumab (Avastin) in children and young adults with refractory or recurrent solid tumors. Ann Oncol. 2008;19:807–813
  151. Jain RK, Duda DG, Clark JW, Loeffler JS. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract. 2006;3:24–40
  152. Bennicelli JL, Barr FG. Chromosomal translocations and sarcomas. Curr Opin Oncol. 2002;14:412–419
  153. Smith R, Owen LA, Trem DJ, et al. Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing’s sarcoma. Cancer Cell. 2006;9:405–416
  154. Bernasconi M, Remppis A, Fredericks WJ, Rauscher FJ, Schafer BW. Induction of apoptosis in rhabdomyosarcoma cells through down-regulation of PAX proteins. Proc Natl Acad Sci USA. 1996;93:13164–13169
  155. Jacobs JF, Coulie PG, Figdor CG, Adema GJ, de Vries IJ, Hoogerbrugge PM. Targets for active immunotherapy against pediatric solid tumors. Cancer Immunol Immunother 2008.
  156. Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science (New York, NY). 2002;298:850–854
  157. Dazzi F, Szydlo RM, Goldman JM. Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: where we now stand. Exp Hematol. 1999;27:1477–1486
  158. Mu LJ, Kyte JA, Kvalheim G, et al. Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients. Br J Cancer. 2005;93:749–756
  159. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004;10:909–915
  160. Dagher R, Long LM, Read EJ, et al. Pilot trial of tumor-specific peptide vaccination and continuous infusion interleukin-2 in patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma: an inter-institute NIH study. Med Pediatr Oncol. 2002;38:158–164
  161. Mackall CL, Rhee EH, Read EJ, et al. A pilot study of consolidative immunotherapy in patients with high-risk pediatric sarcomas. Clin Cancer Res. 2008;14:4850–4858
  162. van den Broeke LT, Pendleton CD, Mackall C, Helman LJ, Berzofsky JA. Identification and epitope enhancement of a PAX-FKHR fusion protein breakpoint epitope in alveolar rhabdomyosarcoma cells created by a tumorigenic chromosomal translocation inducing CTL capable of lysing human tumors. Cancer Res. 2006;66:1818–1823
  163. Amstutz R, Wachtel M, Troxler H, et al. Phosphorylation regulates transcriptional activity of PAX3/FKHR and reveals novel therapeutic possibilities. Cancer Res. 2008;68:3767–3776
  164. Gardner KH, Montminy M. Can you hear me now? Regulating transcriptional activators by phosphorylation. Sci STKE 2005;pe44.
  165. Houghton PJ, Morton CL, Tucker C, et al. The pediatric preclinical testing program: description of models and early testing results. Pediatr Blood Cancer. 2007;49:928–940
  166. Johnson JI, Decker S, Zaharevitz D, et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer. 2001;84:1424–1431
  167. Voskoglou-Nomikos T, Pater JL, Seymour L. Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res. 2003;9:4227–4239
  168. Nardone RM. Eradication of cross-contaminated cell lines: a call for action. Cell Biol Toxicol. 2007;23:367–372
  169. Neale G, Su X, Morton CL, et al. Molecular characterization of the pediatric preclinical testing panel. Clin Cancer Res. 2008;14:4572–4583
  170. Sarfaraz S, Adhami VM, Syed DN, Afaq F, Mukhtar H. Cannabinoids for cancer treatment: progress and promise. Cancer Res. 2008;68:339–342
  171. Wachtel M, Dettling M, Koscielniak E, et al. Gene expression signatures identify rhabdomyosarcoma subtypes and detect a novel t(2;2)(q35;p23) translocation fusing PAX3 to NCOA1. Cancer Res. 2004;64:5539–5545
  172. Davicioni E, Finckenstein FG, Shahbazian V, Buckley JD, Triche TJ, Anderson MJ. Identification of a PAX-FKHR gene expression signature that defines molecular classes and determines the prognosis of alveolar rhabdomyosarcomas. Cancer Res. 2006;66:6936–6946
  173. Croci S, Landuzzi L, Astolfi A, et al. Inhibition of connective tissue growth factor (CTGF/CCN2) expression decreases the survival and myogenic differentiation of human rhabdomyosarcoma cells. Cancer Res. 2004;64:1730–1736
  174. Jin Z, Lahat G, Korchin B, et al. Midkine enhances soft-tissue sarcoma growth: a possible novel therapeutic target. Clin Cancer Res. 2008;14:5033–5042
  175. Cen L, Hsieh FC, Lin HJ, Chen CS, Qualman SJ, Lin J. PDK-1/AKT pathway as a novel therapeutic target in rhabdomyosarcoma cells using OSU-03012 compound. Br J Cancer. 2007;97:785–791
  176. Shor AC, Keschman EA, Lee FY, et al. Dasatinib inhibits migration and invasion in diverse human sarcoma cell lines and induces apoptosis in bone sarcoma cells dependent on SRC kinase for survival. Cancer Res. 2007;67:2800–2808
  177. Marampon F, Ciccarelli C, Zani BM. Down-regulation of c-Myc following MEK/ERK inhibition halts the expression of malignant phenotype in rhabdomyosarcoma and in non muscle-derived human tumors. Mol Cancer. 2006;5:31
  178. Ciccarelli C, Marampon F, Scoglio A, et al. p21WAF1 expression induced by MEK/ERK pathway activation or inhibition correlates with growth arrest, myogenic differentiation, onco-phenotype reversal in rhabdomyosarcoma cells. Mol Cancer. 2005;4:41
  179. Greenberg JA, Somme S, Russnes HE, Durbin AD, Malkin D. The estrogen receptor pathway in rhabdomyosarcoma: a role for estrogen receptor-beta in proliferation and response to the antiestrogen 4′OH-tamoxifen. Cancer Res. 2008;68:3476–3485
  180. Mercer SE, Ewton DZ, Shah S, Naqvi A, Friedman E. Mirk/Dyrk1b mediates cell survival in rhabdomyosarcomas. Cancer Res. 2006;66:5143–5150
  181. Ye L, Zhang H, Zhang L, et al. Effects of RNAi-mediated Smad4 silencing on growth and apoptosis of human rhabdomyosarcoma cells. Int J Oncol. 2006;29:1149–1157
  182. Barlow JW, Wiley JC, Mous M, et al. Differentiation of rhabdomyosarcoma cell lines using retinoic acid. Pediatr Blood Cancer. 2006;47:773–784
  183. Caldas H, Holloway MP, Hall BM, Qualman SJ, Altura RA. Survivin-directed RNA interference cocktail is a potent suppressor of tumour growth in vivo. J Med Genet. 2006;43:119–128
  184. Scotlandi K, Perdichizzi S, Bernard G, et al. Targeting CD99 in association with doxorubicin: an effective combined treatment for Ewing’s sarcoma. Eur J Cancer. 2006;42:91–96
  185. Sanceau J, Poupon MF, Delattre O, Sastre-Garau X, Wietzerbin J. Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide. Oncogene. 2002;21:7700–7709
  186. Guan H, Zhou Z, Gallick GE, et al. Targeting Lyn inhibits tumor growth and metastasis in Ewing’s sarcoma. Mol Cancer Ther. 2008;7:1807–1816
  187. Maehara H, Kaname T, Yanagi K, et al. Midkine as a novel target for antibody therapy in osteosarcoma. Biochem Biophys Res Commun. 2007;358:757–762
  188. Zhang P, Yang Y, Zweidler-McKay PA, Hughes DP. Critical role of notch signaling in osteosarcoma invasion and metastasis. Clin Cancer Res. 2008;14:2962–2969
  189. McGary EC, Heimberger A, Mills L, et al. A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits spontaneous pulmonary metastasis of osteosarcoma cells in vivo. Clin Cancer Res. 2003;9:6560–6566
  190. Contardi E, Palmisano GL, Tazzari PL, et al. CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. Int J Cancer. 2005;117:538–550
  191. Warzecha J, Gottig S, Chow KU, et al. Inhibition of osteosarcoma cell proliferation by the Hedgehog-inhibitor cyclopamine. J Chemother (Florence, Italy). 2007;19:554–561
  192. Dass CR, Friedhuber AM, Khachigian LM, Dunstan DE, Choong PF. Downregulation of c-jun results in apoptosis-mediated anti-osteosarcoma activity in an orthotopic model. Cancer Biol Ther. 2008;7:1033–1036
  193. Dass CR, Khachigian LM, Choong PF. C-Jun knockdown sensitizes osteosarcoma to doxorubicin. Mol Cancer Ther. 2008;7:1909–1912
  194. Wang R, Dong K, Lin F, et al. Inhibiting proliferation and enhancing chemosensitivity to taxanes in osteosarcoma cells by RNA interference-mediated downregulation of stathmin expression. Mol Med. 2007;13:567–575
  195. Zhang HZ, Wang Y, Gao P, et al. Silencing stathmin gene expression by survivin promoter-driven siRNA vector to reverse malignant phenotype of tumor cells. Cancer Biol Ther. 2006;5:1457–1461
  196. Yuan K, Chung LW, Siegal GP, Zayzafoon M. Alpha-CaMKII controls the growth of human osteosarcoma by regulating cell cycle progression. Lab Invest. 2007;87:938–950
  197. Sato N, Mizumoto K, Maehara N, et al. Enhancement of drug-induced apoptosis by antisense oligodeoxynucleotides targeted against Mdm2 and p21WAF1/CIP1. Anticancer Res. 2000;20:837–842
  198. Spreafico A, Schenone S, Serchi T, et al. Antiproliferative and proapoptotic activities of new pyrazolo[3,4-d]pyrimidine derivative Src kinase inhibitors in human osteosarcoma cells. FASEB J. 2008;22:1560–1571

PII: S0305-7372(10)00027-7

doi: 10.1016/j.ctrv.2010.02.007

Cancer Treatment Reviews
Volume 36, Issue 4 , Pages 318-327 , June 2010

Article Tools