R. Ladenstein, U. Pötschger, and M. C. Le-deley, Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial, Journal of Clinical Oncology, vol.28, issue.20, pp.3284-3291, 2010.

O. Oberlin, M. C. Deley, and B. N. Bui, Prognostic factors in localized Ewing's tumours and peripheral neuroectodermal tumours: the third study of the french society of paediatric oncology (EW88 study), British Journal of Cancer, vol.85, issue.11, pp.1646-1654, 2001.

M. C. Le-deley, J. M. Guinebretière, and J. C. Gentet, SFOP OS94: a randomised trial comparing preoperative high-dose methotrexate plus doxorubicin to high-dose methotrexate plus etoposide and ifosfamide in osteosarcoma patients, European Journal of Cancer, vol.43, issue.4, pp.752-761, 2007.

E. E. Pakos, A. D. Nearchou, and R. J. Grimer, Prognostic factors and outcomes for osteosarcoma: an international collaboration, European Journal of Cancer, vol.45, issue.13, pp.2367-2375, 2009.

M. Stahl, A. Ranft, and M. Paulussen, Risk of recurrence and survival after relapse in patients with Ewing sarcoma, Pediatric Blood and Cancer, vol.57, issue.4, pp.549-553, 2011.

F. Tirode, K. Laud-duval, A. Prieur, B. Delorme, P. Charbord et al., Mesenchymal stem cell features of Ewing tumors, Cancer Cell, vol.11, issue.5, pp.421-429, 2007.

S. Benini, M. C. Manara, and V. Cerisano, Contribution of MEK/MAPK and PI3-K signaling pathway to the malignant behavior of Ewing's sarcoma cells: therapeutic prospects, International Journal of Cancer, vol.108, issue.3, pp.358-366, 2004.

H. V. Erkizan, V. N. Uversky, and J. A. Toretsky, Oncogenic partnerships: EWS-FLI1 protein interactions initiate key pathways of Ewing's sarcoma, Clinical Cancer Research, vol.16, issue.16, pp.4077-4083, 2010.

K. Tanaka, T. Iwakuma, K. Harimaya, H. Sato, and Y. Iwamoto, EWS-Fli1 antisense oligodeoxynucleotide inhibits proliferation of human Ewing's sarcoma and primitive neuroectodermal tumor cells, Journal of Clinical Investigation, vol.99, issue.2, pp.239-247, 1997.

A. Maksimenko, G. Lambert, J. R. Bertrand, E. Fattal, P. Couvreur et al., Therapeutic potentialities of EWS-Fli-1 mRNA-targeted vectorized antisense oligonucleotides, Annals of the New York Academy of Sciences, vol.1002, pp.72-77, 2003.

S. Hu-lieskovan, J. D. Heidel, D. W. Bartlett, M. E. Davis, and T. J. Triche, Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma, Cancer Research, vol.65, issue.19, pp.8984-8992, 2005.

P. J. Grohar, G. M. Woldemichael, and L. B. Griffin, Identification of an inhibitor of the EWS-FLI1 oncogenic transcription factor by high-throughput screening, Journal of the National Cancer Institute, vol.103, issue.12, pp.962-978, 2011.

H. V. Erkizan, Y. Kong, and M. Merchant, A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma, Nature Medicine, vol.15, issue.7, pp.750-756, 2009.

S. Baruchel, A. Pappo, and M. Krailo, A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: a report from the Children's Oncology Group, European Journal of Cancer, vol.48, issue.4, pp.579-585, 2012.

P. J. Grohar, L. B. Griffin, and C. Yeung, Ecteinascidin 743 interferes with the activity of EWS-FLI1 in ewing sarcoma cells, Neoplasia, vol.13, issue.2, pp.145-153, 2011.

L. Lau, J. G. Supko, and S. Blaney, A phase I and pharmacokinetic study of ecteinascidin-743 (Yondelis) in children with refractory solid tumors. A Children's Oncology Group study, Clinical Cancer Research, vol.11, issue.2 I, pp.672-677, 2005.

S. Delaloge, A. Yovine, and A. Taamma, Ecteinascidin-743: a marine-derived compound in advanced, pretreated sarcoma patients-preliminary evidence of activity, Journal of Clinical Oncology, vol.19, issue.5, pp.1248-1255, 2001.

A. Le-cesne, A. Yovine, and J. Y. Blay, A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials, Investigational New Drugs, vol.30, pp.1193-1202, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00849986

S. Mateo-lozano, P. C. Gokhale, V. A. Soldatenkov, A. Dritschilo, O. M. Tirado et al., Combined transcriptional and translational targeting of EWS/FLI-1 in Ewing's sarcoma, Clinical Cancer Research, vol.12, issue.22, pp.6781-6790, 2006.

W. D. Tap, AMG 479 in relapsed or refractory Ewing's family tumors (EFT) or desmoplastic small round cell tumors (DSRCT): phase II results, Journal of Clinical Oncology, vol.28, p.15, 2010.

D. Olmos, S. Postel-vinay, and L. R. Molife, Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study, The Lancet Oncology, vol.11, issue.2, pp.129-135, 2010.

A. S. Pappo, S. R. Patel, and J. Crowley, R1507, a monoclonal antibody to the insulin-like growth factor 1 receptor, in patients with recurrent or refractory Ewing sarcoma family of tumors: results of a phase II Sarcoma Alliance for Research through Collaboration study, Journal of Clinical Oncology, vol.29, issue.34, pp.4541-4547, 2010.

H. Juergens, N. C. Daw, and B. Geoerger, Preliminary efficacy of the anti-insulin-like growth factor type 1 receptor antibody figitumumab in patients with refractory Ewing sarcoma, Journal of Clinical Oncology, vol.29, issue.34, pp.4534-4540, 2011.

S. Malempati, B. Weigel, and A. M. Ingle, Phase I/II trial and pharmacokinetic study of cixutumumab in pediatric patients with refractory solid tumors and Ewing sarcoma: a report from the Children's Oncology Group, Journal of Clinical Oncology, vol.30, issue.3, pp.256-262, 2012.

P. Anderson, K. Skubitz, and R. Miller, Activity of SCH 717454 in subjects with relapsed osteosarcoma or Ewing's sarcoma (study P04720), Proceedings of the 14th Annual Meeting of the Connective Tissue Oncology Society, 2007.

A. L. Ho and G. K. Schwartz, Targeting of insulin-like growth factor type 1 receptor in Ewing sarcoma: unfulfilled promise or a promising beginning?, Journal of Clinical Oncology, vol.29, issue.34, pp.4581-4583, 2011.

K. Scotlandi, M. C. Manara, and M. Serra, Expression of insulin-like growth factor system components in Ewing's sarcoma and their association with survival, European Journal of Cancer, vol.47, issue.8, pp.1258-1266, 2011.

C. Garofalo, M. C. Manara, and G. Nicoletti, Efficacy of and resistance to anti-IGF-1R therapies in Ewing's sarcoma is dependent on insulin receptor signaling, Oncogene, vol.30, issue.24, pp.2730-2740, 2011.

Y. Gazitt, V. Kolaparthi, K. Moncada, C. Thomas, and J. Freeman, Targeted therapy of human osteosarcoma with 17AAG or rapamycin: characterization of induced apoptosis and inhibition of mTOR and Akt/MAPK/Wnt pathways, International Journal of Oncology, vol.34, issue.2, pp.551-561, 2009.

X. Wan, A. Mendoza, C. Khanna, and L. J. Helman, Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma, Cancer Research, vol.65, issue.6, pp.2406-2411, 2005.

J. Mora, E. Rodríguez, and C. Torres, Activated growth signaling pathway expression in Ewing sarcoma and clinical outcome, Pediatric Blood & Cancer, vol.58, issue.4, pp.532-538, 2012.

M. Fouladi, F. Laningham, and J. Wu, Phase I study of everolimus in pediatric patients with refractory solid tumors, Journal of Clinical Oncology, vol.25, issue.30, pp.4806-4812, 2007.

S. L. Spunt, S. A. Grupp, and T. A. Vik, Phase I study of temsirolimus in pediatric patients with recurrent/refractory solid tumors, Journal of Clinical Oncology, vol.29, issue.21, pp.2933-2940, 2011.

S. P. Chawla, A. P. Staddon, and L. H. Baker, Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas, Journal of Clinical Oncology, vol.30, issue.1, pp.78-84, 2012.
URL : https://hal.archives-ouvertes.fr/hal-01058262

S. P. Chawla, Results of the phase III, placebo-controlled trial (SUCCEED) evaluating the mTOR inhibitor ridaforolimus (R) as maintenance therapy in advanced sarcoma patients (pts) following clinical benefit from prior standard cytotoxic chemotherapy (CT), Journal of Clinical Oncology, vol.29, 2011.

A. Naing, P. Lorusso, and S. Fu, Insulin Growth Factor-Receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with refractory Ewing's sarcoma family tumors, Clinical Cancer Research, vol.18, issue.9, pp.2625-2631, 2012.

T. Kubo, S. Piperdi, and J. Rosenblum, Platelet-derived growth factor receptor as a prognostic marker and a therapeutic target for imatinib mesylate therapy in osteosarcoma, Cancer, vol.112, issue.10, pp.2119-2129, 2008.

M. S. Merchant, C. W. Woo, C. L. Mackall, and C. J. Thiele, Potential use of imatinib in Ewing's sarcoma: evidence for in vitro and in vivo activity, Journal of the National Cancer Institute, vol.94, issue.22, pp.1673-1679, 2002.

M. Hotfilder, C. Lanvers, H. Jürgens, J. Boos, and J. Vormoor, C-KIT-expressing Ewing tumour cells are insensitive to imatinib mesylate (STI571), Cancer Chemotherapy and Pharmacology, vol.50, issue.2, pp.167-169, 2002.

R. Chugh, J. K. Wathen, and R. G. Maki, Phase II multicenter trial of imatinib in 10 histologic subtypes of sarcoma using a bayesian hierarchical statistical model, Journal of Clinical Oncology, vol.27, issue.19, pp.3148-3153, 2009.

J. Chao, G. T. Budd, and P. Chu, Phase II clinical trial of imatinib mesylate in therapy of KIT and/or PDGFR?expressing ewing sarcoma family of tumors and desmoplastic small round cell tumors, AntiCancer Research, vol.30, issue.2, pp.547-552, 2010.

M. Bond, M. L. Bernstein, and A. Pappo, A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: a children's oncology group study, Pediatric Blood and Cancer, vol.50, issue.2, pp.254-258, 2008.

I. González, E. J. Andreu, and A. Panizo, 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, Clinical Cancer Research, vol.10, issue.2, pp.751-761, 2004.

F. Timeus, N. Crescenzio, A. Fandi, A. Doria, L. Foglia et al., In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines, Oncology Reports, vol.19, issue.2, pp.353-359, 2008.

P. Hingorani, W. Zhang, R. Gorlick, and E. A. Kolb, Inhibition of Src phosphorylation alters metastatic potential of osteosarcoma in vitro but not in vivo, Clinical Cancer Research, vol.15, issue.10, pp.3416-3422, 2009.

R. Aplenc, S. M. Blaney, and L. C. Strauss, Pediatric phase I trial and pharmacokinetic study of dasatinib: a report from the children's oncology group phase I consortium, Journal of Clinical Oncology, vol.29, issue.7, pp.839-844, 2011.

Y. Pignochino, G. Grignani, and G. Cavalloni, Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways, Molecular Cancer, vol.8, 2009.

G. Grignani, E. Palmerini, and P. Dileo, A phase II trial of sorafenib in relapsed and unresectable high-grade 10 osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study, Annals of Oncology, vol.23, issue.2, pp.508-516, 2012.

J. M. Maris, J. Courtright, and P. J. Houghton, Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program, Pediatric Blood and Cancer, vol.51, issue.1, pp.42-48, 2008.

, Sarcoma

S. G. Dubois, S. Shusterman, and J. M. Reid, Tolerability and pharmacokinetic profile of a sunitinib powder formulation in pediatric patients with refractory solid tumors: a Children's Oncology Group study, Cancer Chemother Pharmacol, vol.69, issue.4, pp.1021-1027, 2012.

S. G. Dubois, S. Shusterman, and A. M. Ingle, Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: a children's oncology group study, Clinical Cancer Research, vol.17, issue.15, pp.5113-5122, 2011.

S. T. Keir, J. M. Maris, and R. Lock, Initial testing (stage 1) of the multi-targeted kinase inhibitor sorafenib by the pediatric preclinical testing program, Pediatric Blood and Cancer, vol.55, issue.6, pp.1126-1133, 2010.

S. Kumar, R. B. Mokhtari, and R. Sheikh, Metronomic oral topotecan with pazopanib is an active antiangiogenic regimen in mouse models of aggressive pediatric solid tumor, Clinical Cancer Research, vol.17, issue.17, pp.5656-5667, 2011.

J. L. Bender, A. Lee, and P. C. Adamson, Phase I study of pazopanib in children with relapsed or refractory solid tumors (ADVL0815): a Children's Oncology Group Phase I Consortium Trial, Journal of Clinical Oncology, vol.29, 2011.

T. Bachelot, C. Bourgier, and C. Cropet, Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study, Journal of Clinical Oncology, vol.30, issue.22, pp.2718-2724, 2012.

H. S. Rugo and S. Keck, Reversing hormone resistance: have we found the golden key?, Journal of Clinical Oncology, vol.30, issue.22, pp.2707-2709, 2012.

W. Fu, M. Le, and B. Chu, The cyclin-dependent kinase inhibitor SCH 727965 (dinacliclib) induces the apoptosis of osteosarcoma cells, Molecular Cancer Therapeutics, vol.10, issue.6, pp.1018-1027, 2011.

S. P. Chawla, V. S. Chua, and L. Fernandez, Phase I/II and phase II studies of targeted gene delivery In vivo: intravenous rexin-g for chemotherapy-resistant sarcoma and osteosarcoma, Molecular Therapy, vol.17, issue.9, pp.1651-1657, 2009.

J. M. Maris, C. L. Morton, and R. Gorlick, Initial testing of the Aurora kinase a inhibitor MLN8237 by the Pediatric Preclinical Testing Program (PPTP), Pediatric Blood and Cancer, vol.55, issue.1, pp.26-34, 2010.

A. G. Morales, M. S. Brassesco, and J. A. Pezuk, BI 2536-mediated PLK1 inhibition suppresses HOS and MG-63 osteosarcoma cell line growth and clonogenicity, Anti-Cancer Drugs, vol.22, pp.995-1001, 2011.

L. T. Vassilev, B. T. Vu, and B. Graves, In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2, Science, vol.303, issue.5659, pp.844-848, 2004.

C. Tovar, J. Rosinski, and Z. Filipovic, Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy, Proceedings of the National Academy of Sciences of the United States of America, vol.103, issue.6, pp.1888-1893, 2006.

J. Sonnemann, C. D. Palani, and S. Wittig, Anticancer effects of the p53 activator nutlin-3 in Ewing's sarcoma cells, European Journal of Cancer, vol.47, issue.9, pp.1432-1441, 2011.

D. Javelaud and F. Besançon, NF-?B activation results in rapid inactivation of JNK in TNF?-treated Ewing sarcoma cells: a mechanism for the anti-apoptotic effect of NF-?B, Oncogene, vol.20, issue.32, pp.4365-4372, 2001.

C. D. Palani, J. F. Beck, and J. Sonnemann, Histone deacetylase inhibitors enhance the anticancer activity of nutlin-3 and induce p53 hyperacetylation and downregulation of MDM2 and MDM4 gene expression, Investigational New Drugs, pp.1-12, 2010.

S. Bruheim, Y. Xi, J. Ju, and O. Fodstad, Gene expression profiles classify human osteosarcoma xenografts according to sensitivity to doxorubicin, cisplatin, and ifosfamide, Clinical Cancer Research, vol.15, issue.23, pp.7161-7169, 2009.

M. Puglisi, L. Van-doorn, and M. Blanco-codesido, A phase I safety and pharmacokinetic (PK) study of navitoclax (N) in combination with docetaxel (D) in patients (pts) with solid tumors, Journal of Clinical Oncology, vol.29, 2011.

G. Picarda, F. Lamoureux, and L. Geffroy, Preclinical evidence that use of TRAIL in Ewing's sarcoma and osteosarcoma therapy inhibits tumor growth, prevents osteolysis, and increases animal survival, Clinical Cancer Research, vol.16, issue.8, pp.2363-2374, 2010.

Y. Wang, D. Mandal, and S. Wang, Platelet-derived growth factor receptor ? inhibition increases tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL) sensitivity: imatinib and TRAIL dual therapy, Cancer, vol.116, issue.16, pp.3892-3902, 2010.

P. J. Kaplan-lefko, J. D. Graves, and S. J. Zoog, Conatumumab, a fully human agonist antibody to death receptor 5, induces apoptosis via caspase activation in multiple tumor types, Cancer Biology and Therapy, vol.9, issue.8, pp.618-631, 2010.

S. P. Chawla, A. C. Lockhart, and N. Azad, Efficacy and safety of conatumumab plus AMG 479 in patients with advanced sarcoma, Proceedings of the CTOS Meeting, 2010.

G. D. Demetri, A. L. Cesne, and S. P. Chawla, First-line treatment of metastatic or locally advanced unresectable soft tissue sarcomas with conatumumab in combination with doxorubicin or doxorubicin alone: a phase I/II open-label and double-blind study, European Journal of Cancer, vol.48, issue.4, pp.547-563, 2012.

P. J. Houghton, M. H. Kang, and C. P. Reynolds, Initial testing (stage 1) of LCL161, a SMAC mimetic, by the pediatric preclinical testing program, Pediatr Blood Cancer, vol.58, issue.4, pp.636-639, 2012.

S. V. Holt, K. E. Brookes, C. Dive, and G. W. Makin, Down-regulation of XIAP by AEG35156 in paediatric tumour cells induces apoptosis and sensitises cells to cytotoxic agents, Oncology Reports, vol.25, issue.4, pp.1177-1181, 2011.

J. C. Brenner, F. Y. Feng, and S. Han, PARP-1 inhibition as a targeted strategy to treat Ewing's sarcoma, Cancer Research, vol.72, issue.7, pp.1608-1613, 2012.

Y. F. Wu, X. J. Liang, and Y. Y. Liu, +Antisense oligonucleotide targeting survivin inhibits growth by inducing apoptosis in human osteosarcoma cells MG-63, Neoplasma, vol.57, issue.6, pp.501-506, 2010.

J. Zou, M. Gan, N. Mao, X. Zhu, Q. Shi et al., Sensitization of osteosarcoma cell line SaOS-2 to chemotherapy by downregulating survivin, Archives of Medical Research, vol.41, issue.3, pp.162-169, 2010.

J. Huang, K. Liu, and Y. Yu, Targeting HMGB1-mediated autophagy as a novel therapeutic strategy for osteosarcoma, Autophagy, vol.8, issue.2, pp.275-277, 2012.

J. Huang, J. Ni, and K. Liu, HMGB1 promotes drug resistance in osteosarcoma, Cancer Research, vol.72, issue.1, pp.230-238, 2012.

N. V. Rao, B. Argyle, and X. Xu, Low anticoagulant heparin targets multiple sites of inflammation, suppresses heparininduced thrombocytopenia, and inhibits interaction of RAGE with its ligands, American Journal of Physiology, vol.299, issue.1, pp.97-110, 2010.

E. Sotillo-piñeiro, L. Sierrasesúmaga, and A. Patiño-garcía, Telomerase activity and telomere length in primary and metastatic tumors from pediatric bone cancer patients, Pediatric Research, vol.55, issue.2, pp.231-235, 2004.

J. Fujimori, T. Matsuo, and S. Shimose, Antitumor effects of telomerase inhibitor TMPyP4 in osteosarcoma cell lines, Journal of Orthopaedic Research, vol.29, pp.1707-1711, 2011.

A. Takahashi, F. Higashino, and M. Aoyagi, EWS/ETS fusions activate telomerase in Ewing's tumors, Cancer Research, vol.63, issue.23, pp.8338-8344, 2003.

K. Trieb and H. Blahovec, Suramin suppresses growth, alkaline-phosphatase and telomerase activity of human osteosarcoma cells in vitro, International Journal of Biochemistry and Cell Biology, vol.35, issue.7, pp.1066-1070, 2003.

O. Uziel, E. Fenig, and J. Nordenberg, Imatinib mesylate (Gleevec) downregulates telomerase activity and inhibits proliferation in telomerase-expressing cell lines, British Journal of Cancer, vol.92, issue.10, pp.1881-1891, 2005.

C. Lanvers-kaminsky, B. Winter, and S. Koling, Doxorubicin modulates telomerase activity in Ewing's sarcoma in vitro and in vivo, Oncology Reports, vol.14, issue.3, pp.751-758, 2005.

A. Schuck, C. Poremba, and C. Lanvers, Radiation-induced changes of telomerase activity in a human Ewing xenograft tumor, Strahlentherapie und Onkologie, vol.178, issue.12, pp.701-708, 2002.

K. S. Stewart and E. S. Kleinerman, Tumor vessel development and expansion in Ewing's sarcoma: a review of the vasculogenesis process and clinical trials with vasculartargeting agents, Sarcoma, vol.2011, 2011.

H. Mizobuchi, J. M. García-castellano, S. Philip, J. H. Healey, and R. Gorlick, Hypoxia markers in human osteosarcoma: an exploratory study, Clinical Orthopaedics and Related Research, vol.466, issue.9, pp.2052-2059, 2008.

J. Bajpai, M. Sharma, and V. Sreenivas, VEGF expression as a prognostic marker in osteosarcoma, Pediatric Blood and Cancer, vol.53, issue.6, pp.1035-1039, 2009.

Q. C. Yang, B. F. Zeng, and Z. M. Shi, Inhibition of hypoxiainduced angiogenesis by trichostatin A via suppression of HIF-1a activity in human osteosarcoma, Journal of Experimental and Clinical Cancer Research, vol.25, issue.4, pp.593-599, 2006.

D. N. Aryee, S. Niedan, and M. Kauer, Hypoxia modulates EWS-FLI1 transcriptional signature and enhances the malignant properties of Ewing's Sarcoma cells In vitro, Cancer Research, vol.70, issue.10, pp.4015-4023, 2010.

Q. C. Yang, B. F. Zeng, Y. Dong, Z. M. Shi, Z. M. Jiang et al., Overexpression of hypoxia-inducible factor-1? in human osteosarcoma: correlation with clinicopathological parameters and survival outcome, Japanese Journal of Clinical Oncology, vol.37, issue.2, pp.127-134, 2007.

H. J. Knowles, K. L. Schaefer, U. Dirksen, and N. A. Athanasou, Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor, BMC Cancer, vol.10, p.372, 2010.

J. M. Maris, J. Courtright, and P. J. Houghton, Initial testing of the VEGFR inhibitor AZD2171 by the Pediatric Preclinical Testing Program, Pediatric Blood and Cancer, vol.50, issue.3, pp.581-587, 2008.

C. L. Morton, J. M. Maris, and S. T. Keir, Combination testing of cediranib (AZD2171) against childhood cancer models by the pediatric preclinical testing program, Pediatric Blood & Cancer, vol.58, issue.4, pp.566-571, 2012.

E. Pencreach, E. Guérin, and C. Nicolet, Marked activity of irinotecan and rapamycin combination toward colon cancer cells in vivo and in vitro is mediated through cooperative modulation of the mammalian target of rapamycin/hypoxialnducible factor-1? axis, Clinical Cancer Research, vol.15, issue.4, pp.1297-1307, 2009.

J. Posthumadeboer, M. A. Witlox, G. J. Kaspers, and B. J. Van-royen, Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature, Clinical and Experimental Metastasis, vol.28, issue.5, pp.493-503, 2011.

D. P. Hughes, How the NOTCH pathway contributes to the ability of osteosarcoma cells to metastasize, Cancer Treatment and Research, vol.152, pp.479-496, 2009.

F. Baliko, T. Bright, R. Poon, B. Cohen, S. E. Egan et al., Inhibition of notch signaling induces neural differentiation in Ewing sarcoma, American Journal of Pathology, vol.170, issue.5, pp.1686-1694, 2007.

D. J. Deangelo, R. M. Stone, and L. B. Silverman, A phase I clinical trial of the notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and other leukemias, Annual Meeting Proceedings Part I, vol.24, 2006.

M. Fouladi, C. F. Stewart, and J. Olson, Phase I trial of MK-0752 in children with refractory CNS malignancies: a pediatric brain tumor consortium study, Journal of Clinical Oncology, vol.29, issue.26, pp.3529-3534, 2011.

N. Coltella, M. C. Manara, and V. Cerisano, Role of the MET/HGF receptor in proliferation and invasive behavior of osteosarcoma, The FASEB Journal, vol.17, issue.9, pp.1162-1164, 2003.

N. Entz-werle, T. Lavaux, and N. Metzger, Involvement of MET/TWIST/APC combination or the potential role of ossification factors in pediatric high-grade osteosarcoma oncogenesis, Neoplasia, vol.9, issue.8, pp.678-688, 2007.

A. T. Liao, J. Mccleese, S. Kamerling, J. Christensen, and C. A. London, A novel small molecule Met inhibitor, PF2362376, exhibits biological activity against osteosarcoma, Veterinary and Comparative Oncology, vol.5, issue.3, pp.177-196, 2007.

E. R. Sampson, B. A. Martin, and A. E. Morris, The orally bioavailable met inhibitor PF-2341066 inhibits osteosarcoma growth and osteolysis/matrix production in a xenograft model, Journal of Bone and Mineral Research, vol.26, issue.6, pp.1283-1294, 2011.

Y. Cai, A. B. Mohseny, M. Karperien, P. C. Hogendoorn, G. Zhou et al., Inactive Wnt/?-catenin pathway in conventional high-grade osteosarcoma, Journal of Pathology, vol.220, issue.1, pp.24-33, 2010.

L. H. Brail, J. E. Gray, and H. Burris, A phase I doseescalation, pharmacokinetic (PK), and pharmacodynamic (PD) evaluation of intravenous LY2090314 a GSK3 inhibitor administered in combination with pemetrexed and carboplatin, Journal of Clinical Oncology, vol.29, 2011.

L. L. Worth, E. A. Lafleur, S. F. Jia, and E. S. Kleinerman, Fas expression inversely correlates with metastatic potential in osteosarcoma cells, Oncology Reports, vol.9, issue.4, pp.823-827, 2002.

K. Krishnan, C. Khanna, and L. J. Helman, The biology of metastases in pediatric sarcomas, Cancer Journal, vol.11, issue.4, pp.306-313, 2005.

X. Wan, S. Y. Kim, and L. M. Guenther, Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin, Oncogene, vol.28, issue.38, pp.3401-3411, 2009.

I. Tsagaraki, E. C. Tsilibary, and A. K. Tzinia, TIMP-1 interaction with ?v?3 integrin confers resistance to human osteosarcoma cell line MG-63 against TNF-?-induced apoptosis, Cell and Tissue Research, vol.342, issue.1, pp.87-96, 2010.

T. J. Macdonald, C. F. Stewart, and M. Kocak, Phase I clinical trial of cilengitide in children with refractory brain tumors: pediatric brain tumor consortium study PBTC-012, Journal of Clinical Oncology, vol.26, issue.6, pp.919-924, 2008.

G. D. Angulo, M. Hernandez, and J. Morales-arias, Early lymphocyte recovery as a prognostic indicator for high-risk Ewing sarcoma, Journal of Pediatric Hematology/Oncology, vol.29, issue.1, pp.48-52, 2007.

C. Moore, D. Eslin, A. Levy, J. Roberson, V. Giusti et al., Prognostic significance of early lymphocyte recovery in pediatric osteosarcoma, Pediatric Blood and Cancer, vol.55, issue.6, pp.1096-1102, 2010.

J. Sancéau, M. F. Poupon, O. Delattre, X. Sastre-garau, and J. Wietzerbin, Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide, Oncogene, vol.21, issue.50, pp.7700-7709, 2002.

J. Sancéau and J. Wietzerbin, Downregulation of angiogenic factors in Ewing tumor xenografts by the combination of human interferon-? or interferon-? with ifosfamide, Annals of the New York Academy of Sciences, vol.1030, pp.170-178, 2004.

D. Berghuis, S. J. Santos, and H. J. Baelde, Pro-inflammatory chemokine-chemokine receptor interactions within the Ewing sarcoma microenvironment determine CD8+

, T-lymphocyte infiltration and affect tumour progression, Journal of Pathology, vol.223, issue.3, pp.347-357, 2011.

T. Fujiwara, J. Fukushi, and S. Yamamoto, Macrophage infiltration predicts a poor prognosis for human ewing sarcoma, American Journal of Pathology, vol.179, issue.3, pp.1157-1170, 2011.

N. Gaspar, A. Rey, and P. M. Bérard, Risk adapted chemotherapy for localised Ewing's sarcoma of bone: the French EW93 study, European Journal of Cancer, vol.48, issue.9, pp.1376-1385, 2012.

B. Liu, Z. L. Shi, J. Feng, and H. M. Tao, Celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt, Cell Biology International, vol.32, issue.5, pp.494-501, 2008.

A. S. Gendy, A. Lipskar, R. D. Glick, B. M. Steinberg, M. Edelman et al., Selective inhibition of cyclooxygenase-2 suppresses metastatic disease without affecting primary tumor growth in a murine model of Ewing sarcoma, Journal of Pediatric Surgery, vol.46, issue.1, pp.108-114, 2011.

M. Lipinski, K. Braham, and I. Philip, Neuroectodermassociated antigens on Ewing's sarcoma cell lines, Cancer Research, vol.47, issue.1, pp.183-187, 1987.

J. P. Heiner, F. Miraldi, and S. Kallick, Localization of G(D2)-specific monoclonal antibody 3F8 in human osteosarcoma, Cancer Research, vol.47, issue.20, pp.5377-5381, 1987.

A. L. Yu, A. L. Gilman, and M. F. Ozkaynak, Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma, New England Journal of Medicine, vol.363, issue.14, pp.1324-1334, 2010.

A. L. Yu, M. M. Uttenreuther-fischer, and C. S. Huang, Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma, Journal of Clinical Oncology, vol.16, issue.6, pp.2169-2180, 1998.

S. Kailayangiri, B. Altvater, and J. Meltzer, The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting, British Journal of Cancer, vol.106, issue.6, pp.1123-1133, 2012.

E. K. Waller, The role of sargramostim (rhGM-CSF) as immunotherapy, vol.12, pp.22-26, 2007.

C. A. Arndt, N. V. Koshkina, and C. Y. Inwards, Inhaled granulocyte-macrophage colony stimulating factor for first pulmonary recurrence of osteosarcoma: effects on diseasefree survival and immunomodulation. A report from the Children's Oncology Group, Clinical Cancer Research, vol.16, issue.15, pp.4024-4030, 2010.

F. Meyer-wentrup, G. Richter, and S. Burdach, Identification of an immunogenic EWS-FLI1-derived HLA-DRrestricted T helper cell epitope, Pediatric Hematology and Oncology, vol.22, issue.4, pp.297-308, 2005.

T. Kubo, S. Shimose, T. Matsuo, J. Fujimori, K. Arihiro et al., Interferon-?/? receptor as a prognostic marker in osteosarcoma, Journal of Bone and Joint Surgery Series A, vol.93, issue.6, pp.519-526, 2011.

E. P. Buddingh, M. L. Kuijjer, and R. A. Duim, Tumorinfiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: a rationale for treatment with macrophage activating agents, Clinical Cancer Research, vol.17, issue.8, pp.2110-2119, 2011.

J. Whelan, D. Patterson, and M. Perisoglou, The role of interferons in the treatment of osteosarcoma, Pediatric Blood and Cancer, vol.54, issue.3, pp.350-354, 2010.

Z. Li, Q. Xu, H. Peng, R. Cheng, Z. Sun et al., IFN? enhances HOS and U2OS cell lines susceptibility to ?? T cell-mediated killing through the Fas/Fas ligand pathway, International Immunopharmacology, vol.11, issue.4, pp.496-503, 2011.

L. Kager, U. Potschger, and S. Bielack, Review of mifamurtide in the treatment of patients with osteosarcoma, Therapeutics and Clinical Risk Management, vol.6, pp.279-286, 2010.

Y. Wittrant, S. Théoleyre, and C. Chipoy, RANKL/RANK/ OPG: new therapeutic targets in bone tumours and associated osteolysis, Biochimica et Biophysica Acta, vol.1704, issue.2, pp.49-57, 2004.
URL : https://hal.archives-ouvertes.fr/inserm-00669006

D. H. Jones, T. Nakashima, and O. H. Sanchez, Regulation of cancer cell migration and bone metastasis by RANKL, Nature, vol.440, issue.7084, pp.692-696, 2006.

S. Avnet, A. Longhi, and M. Salerno, Increased osteoclast activity is associated with aggressiveness of osteosarcoma, International Journal of Oncology, vol.33, issue.6, pp.1231-1238, 2008.

J. A. Lee, J. S. Jung, and D. H. Kim, RANKL expression is related to treatment outcome of patients with localized, highgrade osteosarcoma, Pediatric Blood and Cancer, vol.56, issue.5, pp.738-743, 2011.

Z. Zhou, H. Guan, X. Duan, and E. S. Kleinerman, Zoledronic acid inhibits primary bone tumor growth in Ewing sarcoma, Cancer, vol.104, issue.8, pp.1713-1720, 2005.

R. Tenta, N. Pitulis, and D. Tiblalexi, Mechanisms of the action of zoledronic acid on human MG-63 osteosarcoma cells, Hormone and Metabolic Research, vol.40, issue.11, pp.737-745, 2008.

T. Iguchi, Y. Miyakawa, and K. Saito, Zoledronate-induced S phase arrest and apoptosis accompanied by DNA damage and activation of the ATM/Chk1/cdc25 pathway in human osteosarcoma cells, International Journal of Oncology, vol.31, issue.2, pp.285-291, 2007.

B. Ory, F. Blanchard, S. Battaglia, F. Gouin, F. Rédini et al., Zoledronic acid activates the DNA S-phase checkpoint and induces osteosarcoma cell death characterized by apoptosis-inducing factor and endonuclease-G translocation independently of p53 and retinoblastoma status, Molecular Pharmacology, vol.71, issue.1, pp.333-343, 2007.

A. Evdokiou, A. Labrinidis, S. Bouralexis, S. Hay, and D. M. Findlay, Induction of cell death of human osteogenic sarcoma cells by zoledronic acid resembles anoikis, Bone, vol.33, issue.2, pp.216-228, 2003.

D. Fu, X. He, S. Yang, W. Xu, T. Lin et al., Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro, BMC Musculoskeletal Disorders, vol.12, p.146, 2011.

D. Heymann, B. Ory, and F. Blanchard, Enhanced tumor regression and tissue repair when zoledronic acid is combined with ifosfamide in rat osteosarcoma, Bone, vol.37, issue.1, pp.74-86, 2005.

A. Labrinidis, S. Hay, V. Liapis, D. M. Findlay, and A. Evdokiou, Zoledronic acid protects against osteosarcomainduced bone destruction but lacks efficacy against pulmonary metastases in a syngeneic rat model, International Journal of Cancer, vol.127, issue.2, pp.345-354, 2010.

C. R. Dass and P. F. Choong, Zoledronic acid inhibits osteosarcoma growth in an orthotopic model, Molecular Cancer Therapeutics, vol.6, issue.12, pp.3263-3270, 2007.

K. Koto, N. Horie, and S. Kimura, Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model, Cancer Letters, vol.274, issue.2, pp.271-278, 2009.

L. Endo-munoz, A. Cumming, and D. Rickwood, Loss of osteoclasts contributes to development of osteosarcoma pulmonary metastases, Cancer Research, vol.70, issue.18, pp.7063-7072, 2010.

M. S. Benassi, A. Chiechi, and F. Ponticelli, Growth inhibition and sensitization to cisplatin by zoledronic acid in osteosarcoma cells, Cancer Letters, vol.250, issue.2, pp.194-205, 2007.

K. Ryu, H. Murata, and K. Koto, Combined effects of bisphosphonate and radiation on osteosarcoma cells, AntiCancer Research, vol.30, issue.7, pp.2713-2720, 2010.

G. A. Odri, S. Dumoucel, and G. Picarda, Zoledronic acid as a new adjuvant therapeutic strategy for Ewing's sarcoma patients, Cancer Research, vol.70, issue.19, pp.7610-7619, 2010.

S. Battaglia, S. Dumoucel, and J. Chesneau, Impact of oncopediatric dosing regimen of zoledronic acid on bone growth: preclinical studies and case report of an osteosarcoma pediatric patient, Journal of Bone and Mineral Research, vol.26, issue.10, pp.2439-2451, 2011.

T. Akiyama, C. R. Dass, Y. Shinoda, H. Kawano, S. Tanaka et al., Systemic RANK-Fc protein therapy is efficacious against primary osteosarcoma growth in a murine model via activity against osteoclasts, Journal of Pharmacy and Pharmacology, vol.62, issue.4, pp.470-476, 2010.

F. Lamoureux, G. Picarda, and J. Rousseau, Therapeutic efficacy of soluble receptor activator of nuclear factor-?B-Fc delivered by nonviral gene transfer in a mouse model of osteolytic osteosarcoma, Molecular Cancer Therapeutics, vol.7, issue.10, pp.3389-3398, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00332021

F. Lamoureux, P. Richard, and Y. Wittrant, Therapeutic relevance of osteoprotegerin gene therapy in osteosarcoma: blockade of the vicious cycle between tumor cell proliferation and bone resorption, Cancer Research, vol.67, issue.15, pp.7308-7318, 2007.

J. Rousseau, V. Escriou, and F. Lamoureux, Formulated siRNAs targeting Rankl prevent osteolysis and enhance chemotherapeutic response in osteosarcoma models, Journal of Bone and Mineral Research, vol.26, issue.10, pp.2452-2462, 2011.

H. Guan, Z. Zhou, Y. Cao, X. Duan, and E. S. Kleinerman, VEGF165 promotes the osteolytic bone destruction of ewing's sarcoma tumors by upregulating RANKL, Oncology Research, vol.18, issue.2-3, pp.117-125, 2009.

R. Taylor, H. J. Knowles, and N. A. Athanasou, Ewing sarcoma cells express RANKL and support osteoclastogenesis, Journal of Pathology, vol.225, issue.2, pp.195-202, 2011.

K. Fizazi, A. Lipton, and X. Mariette, Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates, Journal of Clinical Oncology, vol.27, issue.10, pp.1564-1571, 2009.

D. Thomas, S. P. Chawla, and K. Skubitz, Denosumab treatment of giant cell tumor of bone: interim analysis of an open-label phase II study, Journal of Clinical Oncology, vol.26, 2008.

G. Henriksen, K. Breistøl, Ø. S. Bruland, Ø. Fodstad, and R. H. Larsen, Significant antitumor effect from bone-seeking, ?-particle-emitting 223Ra demonstrated in an experimental skeletal metastases model, Cancer Research, vol.62, issue.11, pp.3120-3125, 2002.

P. Anderson and R. Nuñez, Samarium lexidronam (153Sm-EDTMP): skeletal radiation for osteoblastic bone metastases and osteosarcoma, Expert Review of Anticancer Therapy, vol.7, issue.11, pp.1517-1527, 2007.

D. M. Loeb, R. F. Hobbs, and A. Okoli, Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma, Cancer, vol.116, issue.23, pp.5470-5478, 2010.

C. Parker, S. Nilsson, and D. Heinrich, Updated analysis of the phase III, double-blind, randomized, multinational study of radium-223 chloride in castration-resistant prostate cancer (CRPC) patients with bone metastases (ALSYMPCA), Journal of Clinical Oncology, vol.30, 2012.

M. Hirotsu, T. Setoguchi, and H. Sasaki, Smoothened as a new therapeutic target for human osteosarcoma, Molecular Cancer, vol.9, issue.5, 2010.

E. M. Beauchamp, L. Ringer, and G. Bulut, Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway, Journal of Clinical Investigation, vol.121, issue.1, pp.148-160, 2011.

J. Warzecha, S. Göttig, and K. U. Chow, Inhibition of osteosarcoma cell proliferation by the hedgehog-inhibitor cyclopamine, Journal of Chemotherapy, vol.19, issue.5, pp.554-561, 2007.

, Sarcoma

H. Zhao, W. Guo, C. Peng, T. Ji, and X. Lu, Arsenic trioxide inhibits the growth of Adriamycin resistant osteosarcoma cells through inducing apoptosis, Molecular Biology Reports, vol.37, issue.5, pp.2509-2515, 2010.

J. Kim, J. Y. Tang, and R. Gong, Itraconazole, a commonly used antifungal that inhibits hedgehog pathway activity and cancer growth, Cancer Cell, vol.17, issue.4, pp.388-399, 2010.

M. Fouladi, J. R. Park, and C. F. Stewart, Pediatric phase I trial and pharmacokinetic study of vorinostat: a children's oncology group phase I consortium report, Journal of Clinical Oncology, vol.28, issue.22, pp.3623-3629, 2010.

J. M. Su, X. N. Li, and P. Thompson, Phase 1 study of valproic acid in pediatric patients with refractory solid or CNS tumors: a children's oncology group report, Clinical Cancer Research, vol.17, issue.3, pp.589-597, 2011.

T. Hirose, Y. Sowa, and S. Takahashi, p53-independent induction of Gadd45 by histone deacetylase inhibitor: coordinate regulation by transcription factors Oct-1 and NF-Y, Oncogene, vol.22, issue.49, pp.7762-7773, 2003.

C. Blattmann, S. Oertel, and V. Ehemann, Enhancement of radiation response in osteosarcoma and rhabdomyosarcoma cell lines by histone deacetylase inhibition, International Journal of Radiation Oncology, vol.78, issue.1, pp.237-245, 2010.

L. A. Wittenburg, L. Bisson, B. J. Rose, C. Korch, and D. H. Thamm, The histone deacetylase inhibitor valproic acid sensitizes human and canine osteosarcoma to doxorubicin, Cancer Chemotherapy and Pharmacology, vol.67, issue.1, pp.83-92, 2011.

C. Yang, E. Choy, and F. J. Hornicek, Histone deacetylase inhibitor (HDACI) PCI-24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells, Cancer Chemotherapy and Pharmacology, vol.67, issue.2, pp.439-446, 2011.

N. V. Koshkina, K. Rao-bindal, and E. S. Kleinerman, Effect of the histone deacetylase inhibitor SNDX-275 on Fas signaling in osteosarcoma cells and the feasibility of its topical application for the treatment of osteosarcoma lung metastases, Cancer, vol.117, issue.15, pp.3457-3467, 2011.

K. Watanabe, K. Okamoto, and S. Yonehara, Sensitization of osteosarcoma cells to death receptor-mediated apoptosis by HDAC inhibitors through downregulation of cellular FLIP, Cell Death and Differentiation, vol.12, issue.1, pp.10-18, 2005.

K. Yamanegi, J. Yamane, and K. Kobayashi, Sodium valproate, a histone deacetylase inhibitor, augments the expression of cell-surface NKG2D ligands, MICA/B, without increasing their soluble forms to enhance susceptibility of human osteosarcoma cells to NK cell-mediated cytotoxicity, Oncology Reports, vol.24, issue.6, pp.1621-1627, 2010.

R. Sakimura, K. Tanaka, and F. Nakatani, Antitumor effects of histone deacetylase inhibitor on Ewing's family tumors, International Journal of Cancer, vol.116, issue.5, pp.784-792, 2005.

F. Nakatani, K. Tanaka, and R. Sakimura, Identification of p21WAF1/CIP1 as a direct target of EWS-Fli1 oncogenic fusion protein, Journal of Biological Chemistry, vol.278, issue.17, pp.15105-15115, 2003.

J. Sonnemann, L. Dreyer, and M. Hartwig, Histone deacetylase inhibitors induce cell death and enhance the apoptosisinducing activity of TRAIL in Ewing's sarcoma cells, Journal of Cancer Research and Clinical Oncology, vol.133, issue.11, pp.847-858, 2007.

T. Okada, K. Tanaka, and F. Nakatani, Involvement of Pglycoprotein and MMP1 in resistance to cyclic tetrapeptide subfamily of histone deacetylase inhibitors in the drugresistant osteosarcoma and Ewing's sarcoma cells, International Journal of Cancer, vol.118, issue.1, pp.90-97, 2006.

H. Matsubara, M. Watanabe, and T. Imai, Involvement of extracellular signal-regulated kinase activation in human osteosarcoma cell resistance to the histone deacetylase inhibitor FK228 [(1S, 4S, 7Z, 10S, 16E, 21R)-7-ethylidene-4, 21-bis(propan-2-yl)-2-oxa-12, Journal of Pharmacology and Experimental Therapeutics, vol.13, issue.5, pp.839-848, 2009.

A. S. Martins, J. L. Ordoñez, and A. García-sánchez, 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 Research, vol.68, issue.15, pp.6260-6270, 2008.

R. Bagatell, J. Beliakoff, C. L. David, M. T. Marron, and L. Whitesell, Hsp90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin, International Journal of Cancer, vol.113, issue.2, pp.179-188, 2005.

N. Gaspar, S. Y. Sharp, and S. Pacey, Acquired resistance to 17-Allylamino-17-Demethoxygeldanamycin (17-A AG, Tanespimycin) in glioblastoma cells, Cancer Research, vol.69, issue.5, pp.1966-1975, 2009.