L. Mirabello, R. Troisi, and S. Savage, International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons, International Journal of Cancer, vol.18, issue.1, pp.229-234, 2009.
DOI : 10.1002/ijc.24320

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048853

E. Hauben and P. Hogendoorn, Epidemiology of primary bone tumors and economial aspects of bone metastases, Bone cancer, pp.5-9, 2015.

C. Inwards and J. Suire, Low-grade central osteosarcoma In: IARC, editor. WHO classification of tumours of soft tissue and bone, pp.281-282, 2013.

A. Rosenberg, A. Cleton-jansen, and G. De-pinieux, editor. WHO classification of tumours of soft tissue and bone, pp.282-288, 2013.

A. Oliveira, K. Okada, and J. Suire, Telangiectatic osteosarcoma In: IARC, editor. WHO classification of tumours of soft tissue and bone, pp.289-290, 2013.

R. Kalil and J. Suire, Small cell osteosarcoma In: IARC, editor. WHO classification of tumours of soft tissue and bone, p.291, 2013.

A. Lazar, F. Mertens, and . Parosteal-osteosarcoma, In: IARC, editor. WHO classification of tumours of soft tissue and bone, pp.92-293, 2013.

A. Montag and J. Suire, Periosteal osteosarcoma In: IARC, editor. WHO classification of tumours of soft tissue and bone, p.294, 2013.

L. Wold, E. Mccarthy, and J. Squire, High-grade surface osteosarcoma In: IARC, editor. WHO classification of tumours of soft tissue and bone, pp.295-296, 2013.

D. Heymann and F. Redini, Bone sarcomas: pathogenesis and new therapeutic approaches, IBMS BoneKEy, vol.17, issue.9, pp.402-414, 2011.
DOI : 10.1138/20110531

A. Mohseny and P. Hogendoorn, Concise Review: Mesenchymal Tumors: When Stem Cells Go Mad, STEM CELLS, vol.70, issue.3, pp.397-403, 2011.
DOI : 10.1002/stem.596

A. Mutsaers and C. Walkley, Cells of origin in osteosarcoma: Mesenchymal stem cells or osteoblast committed cells?, Bone, vol.62, pp.56-63, 2014.
DOI : 10.1016/j.bone.2014.02.003

M. Bousquet, C. Noirot, and F. Accadbled, Whole-exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations, Annals of Oncology, vol.27, issue.4, pp.738-744, 2016.
DOI : 10.1093/annonc/mdw009

M. Kovac, C. Blattmann, and S. Ribi, Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency, Nature Communications, vol.104, p.8940, 2015.
DOI : 10.1038/ncomms9940

C. Walkley, R. Qudsi, and V. Sankaran, Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease, Genes & Development, vol.22, issue.12, pp.1662-1676, 2008.
DOI : 10.1101/gad.1656808

P. Lin, M. Pandey, and F. Jin, Targeted mutation of p53 and Rb in mesenchymal cells of the limb bud produces sarcomas in mice, Carcinogenesis, vol.30, issue.10, pp.1789-1795, 2009.
DOI : 10.1093/carcin/bgp180

S. Berman, E. Calo, and A. Landman, Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage, Proceedings of the National Academy of Sciences, vol.105, issue.33, pp.11851-11856, 2008.
DOI : 10.1073/pnas.0805462105

A. Mutsaers, A. Ng, and E. Baker, Modeling distinct osteosarcoma subtypes in vivo using Cre:lox and lineage-restricted transgenic shRNA, Bone, vol.55, issue.1, pp.166-178, 2013.
DOI : 10.1016/j.bone.2013.02.016

Y. Wittrant, S. Théoleyre, and C. Chipoy, OPG: new therapeutic targets in bone tumours and associated osteolysis, Biochim Biophys Acta, vol.1704, pp.49-57, 2004.
DOI : 10.1016/j.bbcan.2004.05.002

URL : https://hal.archives-ouvertes.fr/inserm-00669006

T. Borovski, D. Sousa, E. Melo, F. Vermeulen, and L. , Cancer Stem Cell Niche: The Place to Be, Cancer Research, vol.71, issue.3, pp.634-639, 2011.
DOI : 10.1158/0008-5472.CAN-10-3220

URL : http://hdl.handle.net/11245/1.385902

P. Perrot, J. Rousseau, and A. Bouffaut, Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence, PLoS ONE, vol.17, issue.6, p.10999, 2010.
DOI : 10.1371/journal.pone.0010999.s001

URL : https://hal.archives-ouvertes.fr/inserm-00667931

P. Avril, F. Duteille, and P. Ridel, Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells, Plastic and Reconstructive Surgery, vol.137, issue.3, pp.865-875, 2016.
DOI : 10.1097/01.prs.0000479989.88114.8b

J. Clark, C. Dass, and P. Choong, A review of clinical and molecular prognostic factors in osteosarcoma, Journal of Cancer Research and Clinical Oncology, vol.25, issue.1, pp.281-297, 2008.
DOI : 10.1007/s00432-007-0330-x

D. Allison, S. Caarney, and E. Ahlmann, A Meta-Analysis of Osteosarcoma Outcomes in the Modern Medical Era, Sarcoma, vol.12, issue.2, p.704872, 2012.
DOI : 10.1016/j.ejca.2011.05.030

L. Mirabello, R. Troisi, and S. Savage, Osteosarcoma incidence and survival rates from 1973 to 2004, Cancer, vol.19, issue.112, pp.1531-1543, 2009.
DOI : 10.1002/cncr.24121

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813207

G. Rosen, C. Tan, and A. Sanmaneechai, The rationale for multiple drug chemotherapy in the treatment of osteogenic sarcoma, Cancer, vol.15, issue.S3, pp.936-945, 1975.
DOI : 10.1002/1097-0142(197503)35:3+<936::AID-CNCR2820350714>3.0.CO;2-B

M. Link, A. Goorin, and A. Miser, The Effect of Adjuvant Chemotherapy on Relapse-Free Survival in Patients with Osteosarcoma of the Extremity, New England Journal of Medicine, vol.314, issue.25, pp.1600-1606, 1986.
DOI : 10.1056/NEJM198606193142502

G. Bacci, A. Longhi, and F. Fagioli, Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 year experience at Rizzoli Institute, Italy, European Journal of Cancer, vol.41, issue.18, pp.2836-2845, 2005.
DOI : 10.1016/j.ejca.2005.08.026

J. Whelan, R. Jinks, and A. Mctiernan, Survival from high-grade localised extremity osteosarcoma: combined results and prognostic factors from three European Osteosarcoma Intergroup randomised controlled trials, Annals of Oncology, vol.23, issue.6, pp.1607-1616, 2012.
DOI : 10.1093/annonc/mdr491

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360547

A. Mctiernan, R. Jinks, and M. Sydes, Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extremity osteosarcoma treated with doxorubicin and cisplatin: A report from the European Osteosarcoma Intergroup, European Journal of Cancer, vol.48, issue.5, pp.703-712, 2012.
DOI : 10.1016/j.ejca.2011.09.012

A. Goorin, D. Schwartzentruber, and M. Devidas, Presurgical Chemotherapy Compared With Immediate Surgery and Adjuvant Chemotherapy for Nonmetastatic Osteosarcoma: Pediatric Oncology Group Study POG-8651, Journal of Clinical Oncology, vol.21, issue.8, pp.1574-1580, 2003.
DOI : 10.1200/JCO.2003.08.165

D. Carrle and S. Bielack, Current strategies of chemotherapy in osteosarcoma, International Orthopaedics, vol.42, issue.3, pp.445-451, 2006.
DOI : 10.1007/s00264-006-0192-x

A. Huvos and . Osteogenic-osteosarcoma, Bone tumors: diagnosis, treatment and prognosis Philadelphia: WB Saunders, pp.85-156, 1991.

F. Gouin and M. Heymann, Margins and bone tumors ??? what are we talking about?, Bone cancer, pp.287-291, 2015.
DOI : 10.1016/B978-0-12-416721-6.00025-X

T. Bertrand, A. Cruz, and O. Binitie, Do Surgical Margins Affect Local Recurrence and Survival in Extremity, Nonmetastatic, High-grade Osteosarcoma?, Clinical Orthopaedics and Related Research??, vol.36, issue.3, pp.677-683, 2016.
DOI : 10.1007/s11999-015-4359-x

S. Bielack, B. Kempf-bielack, V. Kalle, and T. , Controversies in childhood osteosarcoma, Minerva Pediatr, vol.65, pp.125-148, 2013.

J. Whelan, S. Bielack, and N. Marina, EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment, Annals of Oncology, vol.26, issue.2, pp.407-414, 2015.
DOI : 10.1093/annonc/mdu526

N. Marina, S. Smeland, and S. Bielack, MAPIE vs MAP as postoperative chemotherapy in patients with a poor response to preoperative chemotherapy for newly-diagnosed osteosarcoma: results from EURAMOS-1, Connective Tissue Oncology Society (CTOS), 2014.

S. Bielack, S. Smeland, and J. Whelan, Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial, Journal of Clinical Oncology, vol.33, issue.20, pp.2279-2287, 2015.
DOI : 10.1200/JCO.2014.60.0734

R. Schwarz, O. Bruland, and A. Cassoni, The Role of Radiotherapy in Oseosarcoma, Cancer Treat Res, vol.152, pp.147-164, 2009.
DOI : 10.1007/978-1-4419-0284-9_7

T. Ozaki, S. Flege, and M. Kevric, Osteosarcoma of the Pelvis: Experience of the Cooperative Osteosarcoma Study Group, Journal of Clinical Oncology, vol.21, issue.2, pp.334-341, 2003.
DOI : 10.1200/JCO.2003.01.142

T. Delaney, L. Park, and S. Goldberg, Radiotherapy for local control of osteosarcoma, International Journal of Radiation Oncology*Biology*Physics, vol.61, issue.2, pp.492-498, 2005.
DOI : 10.1016/j.ijrobp.2004.05.051

C. Errani, A. Longhi, and G. Rossi, Palliative therapy for osteosarcoma, Expert Review of Anticancer Therapy, vol.11, issue.2, pp.217-227, 2011.
DOI : 10.1586/era.10.172

D. Rahn, A. Mundt, and J. Murphy, Clinical outcomes of palliative radiation therapy for children, Practical Radiation Oncology, vol.5, issue.3, pp.183-187, 2015.
DOI : 10.1016/j.prro.2014.08.015

D. Heymann and F. Redini, Targeted therapies for bone sarcomas, BoneKEy Reports, vol.2, p.378, 2013.
DOI : 10.1038/bonekey.2013.112

K. Ando, M. Heymann, and V. Stresing, Current Therapeutic Strategies and Novel Approaches in Osteosarcoma, Cancers, vol.5, issue.2, pp.591-616, 2013.
DOI : 10.3390/cancers5020591

URL : http://doi.org/10.3390/cancers5020591

C. Hattinger, M. Fanelli, and E. Tavani, Advances in emerging drugs for osteosarcoma, Expert Opinion on Emerging Drugs, vol.133, issue.4, pp.495-514, 2015.
DOI : 10.1093/bioinformatics/btp618

S. Burrow, I. Andrulis, and M. Pollak, Expression of insulin-like growth factor receptor, IGF-1, and IGF-2 in primary and metastatic osteosarcoma, Journal of Surgical Oncology, vol.56, issue.1, pp.21-27, 1998.
DOI : 10.1002/(SICI)1096-9098(199809)69:1<21::AID-JSO5>3.0.CO;2-M

T. Jentzsch, B. Robl, and M. Husmann, Worse prognosis of osteosarcoma patients expressing IGF-1 on a tissue microarray, Anticancer Res, vol.34, pp.3881-3889, 2014.

G. Schwartz, W. Tap, and L. Qin, Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, phase 2 trial, The Lancet Oncology, vol.14, issue.4, pp.371-382, 2013.
DOI : 10.1016/S1470-2045(13)70049-4

R. Bagatell, C. Herzog, and T. Trippett, Pharmacokinetically Guided Phase 1 Trial of the IGF-1 Receptor Antagonist RG1507 in Children with Recurrent or Refractory Solid Tumors, Clinical Cancer Research, vol.17, issue.3, pp.611-619, 2011.
DOI : 10.1158/1078-0432.CCR-10-1731

S. Avnet, L. Sciacca, and M. Salerno, Insulin Receptor Isoform A and Insulin-like Growth Factor II as Additional Treatment Targets in Human Osteosarcoma, Cancer Research, vol.69, issue.6, pp.2443-2452, 2009.
DOI : 10.1158/0008-5472.CAN-08-2645

X. Wan, B. Harkavy, and N. Shen, Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism, Oncogene, vol.274, issue.13, pp.1932-1940, 2006.
DOI : 10.1038/sj.onc.1209990

M. Penel-page, I. Ray-coquard, and J. Larcade, Off-label use of targeted therapies in osteosarcomas: data from the French registry OUTC???S (Observatoire de l???Utilisation des Th??rapies Cibl??es dans les Sarcomes), BMC Cancer, vol.38, issue.Supplement 3, p.854, 2015.
DOI : 10.1186/s12885-015-1894-5

A. Ségaliny, M. Tellez-gabriel, and M. Heymann, Receptor tyrosine kinases: Characterisation, mechanism of action and therapeutic interests for bone cancers, Journal of Bone Oncology, vol.4, issue.1, pp.1-12, 2015.
DOI : 10.1016/j.jbo.2015.01.001

R. Chugh, J. Wathen, and R. 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.
DOI : 10.1200/JCO.2008.20.5054

M. Bond, M. 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 & Cancer, vol.111, issue.2, pp.254-258, 2008.
DOI : 10.1002/pbc.21132

R. Aplenc, S. Blaney, and L. 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.
DOI : 10.1200/JCO.2010.30.7231

J. Maris, J. Courtright, and P. Houghton, Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program, Pediatric Blood & Cancer, vol.6, issue.1, pp.42-48, 2008.
DOI : 10.1002/pbc.21535

S. Dubois, S. Shusterman, and A. 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.
DOI : 10.1158/1078-0432.CCR-11-0237

S. Keir, C. Morton, and J. Wu, Initial testing of the multitargeted kinase inhibitor pazopanib by the pediatric preclinical testing program, Pediatric Blood & Cancer, vol.29, issue.3, pp.586-588, 2012.
DOI : 10.1002/pbc.24016

A. Safwat, A. Boysen, and A. Lücke, Pazopanib in metastatic osteosarcoma: Significant clinical response in three consecutive patients, Acta Oncologica, vol.2, issue.10, pp.1451-1454, 2014.
DOI : 10.1200/JCO.2006.07.3049

F. Navid, S. Baker, and M. Mccarville, Phase I and Clinical Pharmacology Study of Bevacizumab, Sorafenib, and Low-Dose Cyclophosphamide in Children and Young Adults with Refractory/Recurrent Solid Tumors, Clinical Cancer Research, vol.19, issue.1, pp.236-246, 2013.
DOI : 10.1158/1078-0432.CCR-12-1897

G. Grignani, E. Palmerini, and P. Dileo, A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study, Annals of Oncology, vol.23, issue.2, pp.508-516, 2012.
DOI : 10.1093/annonc/mdr151

G. Grignani, E. Palmerini, and V. Ferraresi, Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial, The Lancet Oncology, vol.16, issue.1, pp.98-107, 2015.
DOI : 10.1016/S1470-2045(14)71136-2

K. Mross, A. Frost, and S. Steinbild, A Phase I Dose-Escalation Study of Regorafenib (BAY 73-4506), an Inhibitor of Oncogenic, Angiogenic, and Stromal Kinases, in Patients with Advanced Solid Tumors, Clinical Cancer Research, vol.18, issue.9, pp.2658-2667, 2012.
DOI : 10.1158/1078-0432.CCR-11-1900

C. Cooper, M. Park, and D. Blair, Molecular cloning of a new transforming gene from a chemically transformed human cell line, Nature, vol.170, issue.5981, pp.29-33, 1984.
DOI : 10.1038/311029a0

K. Scotlandi, N. Baldini, and M. Oliviero, Expression of Met/hepatocyte growth factor receptor gene and malignant behavior of musculoskeletal tumors, Am J Pathol, vol.149, pp.1209-1219, 1996.

R. Ferracini, P. Angelini, and E. Cagliero, Met oncogene aberrant expression in canine osteosarcoma, Journal of Orthopaedic Research, vol.270, issue.2, pp.253-256, 2000.
DOI : 10.1002/jor.1100180213

Y. Oda, T. Naka, and M. Takeshita, Comparison of histological changes and changes in nm23 and c-MET expression between primary and metastatic sites in osteosarcoma: A clinicopathologic and immunohistochemical study, Human Pathology, vol.31, issue.6, pp.709-716, 2000.
DOI : 10.1053/hupa.2000.8230

E. Sampson, B. Martin, and A. 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.22, issue.6, pp.1283-1294, 2011.
DOI : 10.1002/jbmr.336

K. Wang, Y. Zhuang, and C. Liu, Inhibition of c-Met activation sensitizes osteosarcoma cells to cisplatin via suppression of the PI3K???Akt signaling, Archives of Biochemistry and Biophysics, vol.526, issue.1, pp.38-43, 2012.
DOI : 10.1016/j.abb.2012.07.003

D. Heymann, B. Ory, and F. Gouin, Bisphosphonates: new therapeutic agents for the treatment of bone tumors, Trends in Molecular Medicine, vol.10, issue.7, pp.337-343, 2004.
DOI : 10.1016/j.molmed.2004.05.007

G. Moriceau, B. Ory, and B. Gobin, Therapeutic Approach of Primary Bone Tumours by Bisphosphonates, Current Pharmaceutical Design, vol.16, issue.27, pp.2981-2987, 2010.
DOI : 10.2174/138161210793563554

URL : https://hal.archives-ouvertes.fr/inserm-00511241

B. Ory, F. Blanchard, and S. Battaglia, 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
DOI : 10.1124/mol.106.028837

M. Muraro, O. Mereuta, and F. Carraro, Osteosarcoma cell line growth inhibition by zoledronate-stimulated effector cells, Cellular Immunology, vol.249, issue.2, pp.63-72, 2007.
DOI : 10.1016/j.cellimm.2007.11.005

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.
DOI : 10.1016/j.bone.2005.02.020

C. Dass and P. Choong, Zoledronic acid inhibits osteosarcoma growth in an orthotopic model, Molecular Cancer Therapeutics, vol.6, issue.12, pp.3263-3270, 2007.
DOI : 10.1158/1535-7163.MCT-07-0546

B. Ory, M. Heymann, and A. Kamijo, Zoledronic acid suppresses lung metastases and prolongs overall survival of osteosarcoma-bearing mice, Cancer, vol.91, issue.11, pp.2522-2529, 2005.
DOI : 10.1002/cncr.21530

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.
DOI : 10.1016/j.canlet.2008.09.026

M. 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.
DOI : 10.1016/j.canlet.2006.10.004

T. Ohba, J. Cates, and H. Cole, Pleiotropic effects of bisphosphonates on osteosarcoma, Bone, vol.63, pp.110-120, 2014.
DOI : 10.1016/j.bone.2014.03.005

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.
DOI : 10.1158/0008-5472.CAN-09-4291

S. Piperno-neumann, L. Deley, M. Rédini, and F. , 1413OZOLEDRONATE DOES NOT REDUCE THE RISK OF TREATMENT FAILURE IN OSTEOSARCOMA: RESULTS OF THE FRENCH MULTICENTRE OS2006 RANDOMISED TRIAL, Annals of Oncology, vol.25, issue.suppl_4, pp.494-510, 2014.
DOI : 10.1093/annonc/mdu354.2

B. Ory, G. Moriceau, and V. Trichet, Farnesyl diphosphate synthase is involved in the resistance to zoledronic acid of osteosarcoma cells, Journal of Cellular and Molecular Medicine, vol.14, issue.3, pp.928-994, 2008.
DOI : 10.1111/j.1582-4934.2008.00141.x

URL : https://hal.archives-ouvertes.fr/inserm-00667523

A. Yoshiyama, T. Morii, and K. Ohtsuka, Development of stemness in cancer cell lines resistant to the anticancer effects of zoledronic acid, Anticancer Res, vol.36, pp.625-631, 2016.

F. Dieli, N. Gebbia, and F. Poccia, Induction of ???? T-lymphocyte effector functions by bisphosphonate zoledronic acid in cancer patients in vivo, Blood, vol.102, issue.6, pp.2310-2311, 2003.
DOI : 10.1182/blood-2003-05-1655

Z. Li, H. Peng, and Q. Xu, Sensitization of human osteosarcoma cells to V??9V??2 T-cell-mediated cytotoxicity by zoledronate, Journal of Orthopaedic Research, vol.171, issue.5, pp.824-830, 2012.
DOI : 10.1002/jor.21579

S. Theoleyre, Y. Wittrant, K. Tat, and S. , The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling, Cytokine & Growth Factor Reviews, vol.15, issue.6, pp.457-475, 2004.
DOI : 10.1016/j.cytogfr.2004.06.004

K. Mori, L. Goff, B. Berreur, and M. , Human osteosarcoma cells express functional receptor activator of nuclear factor-kappa B, The Journal of Pathology, vol.186, issue.5, pp.555-562, 2007.
DOI : 10.1002/path.2140

K. Trieb and R. Windhager, Receptor activator of nuclear factor ??B expression is a prognostic factor in human osteosarcoma, Oncology Letters, vol.10, pp.1813-1815, 2015.
DOI : 10.3892/ol.2015.3489

Z. Bago-horvath, K. Schmid, and F. Rössler, Impact of RANK signalling on survival and chemotherapy response in osteosarcoma, Pathology, vol.46, issue.5, pp.411-415, 2014.
DOI : 10.1097/PAT.0000000000000116

J. Lee, J. Jung, and D. Kim, RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma, Pediatric Blood & Cancer, vol.116, issue.5, pp.738-743, 2011.
DOI : 10.1002/pbc.22720

D. Branstetter, K. Rohrbach, and L. Huang, RANK and RANK ligand expression in primary human osteosarcoma, Journal of Bone Oncology, vol.4, issue.3, pp.59-68, 2014.
DOI : 10.1016/j.jbo.2015.06.002

URL : http://doi.org/10.1016/j.jbo.2015.06.002

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.
DOI : 10.1158/1535-7163.MCT-08-0497

URL : https://hal.archives-ouvertes.fr/inserm-00332021

B. Qiao, W. Shui, and L. Cai, Human mesenchymal stem cells as delivery of&nbsp;osteoprotegerin gene: homing and therapeutic effect for osteosarcoma, Drug Design, Development and Therapy, vol.9, pp.969-976, 2015.
DOI : 10.2147/DDDT.S77116

Y. Chen, D. Grappa, M. Molyneux, and S. , RANKL blockade prevents and treats aggressive osteosarcomas, Science Translational Medicine, vol.7, issue.317, pp.317-197, 2015.
DOI : 10.1126/scitranslmed.aad0295

W. Tan, W. Zhang, and A. Strasner, Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL???RANK signalling, Nature, vol.468, issue.7335, pp.548-553, 2011.
DOI : 10.1038/nature09707

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166217

B. Gobin, M. Baud-'huin, and B. Isidor, Monoclonal antibodies targeting RANKL in bone metastasis treatment, Monoclonal antibodies in oncology. Uckum: eBook Future Medicine Ltd, pp.42-53, 2012.
DOI : 10.2217/ebo.12.295

R. Cathomas, C. Rothermundt, and B. Bode, RANK Ligand Blockade with Denosumab in Combination with Sorafenib in Chemorefractory Osteosarcoma: A Possible Step Forward?, Oncology, vol.88, issue.4, pp.257-260, 2015.
DOI : 10.1159/000369975

C. Derenzo and S. Gottschalk, Genetically Modified T-Cell Therapy for Osteosarcoma, Adv Exp Med Biol, vol.804, pp.323-340, 2014.
DOI : 10.1007/978-3-319-04843-7_18

Z. Li, Potential of human ???? T cells for immunotherapy of osteosarcoma, Molecular Biology Reports, vol.15, issue.1, pp.427-437, 2013.
DOI : 10.1007/s11033-012-2077-y

N. Tarek and D. Lee, Natural Killer Cells for Osteosarcoma, Adv Exp Med Biol, vol.804, pp.341-353, 2014.
DOI : 10.1007/978-3-319-04843-7_19

L. Endo-munoz, A. Evdokiou, and N. Saunders, The role of osteoclasts and tumour-associated macrophages in osteosarcoma metastasis, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, vol.1826, issue.2, pp.434-442, 2012.
DOI : 10.1016/j.bbcan.2012.07.003

I. Kurzman, F. Shi, and D. Vail, Enhancement of Canine Pulmonary Alveolar Macrophage Cytotoxic Activity Against Canine Osteosarcoma Cells, Cancer Biotherapy & Radiopharmaceuticals, vol.14, issue.2, pp.121-128, 1999.
DOI : 10.1089/cbr.1999.14.121

I. Kurzman, E. Macewen, and R. Rosenthal, Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin, Clin Cancer Res, vol.1, pp.1595-1601, 1995.

E. Macewen, I. Kurzman, and S. Helfand, Current Studies of Liposome Muramyl Tripeptide (CGP 19835A Lipid) Therapy for Metastasis in Spontaneous Tumors: A Progress Review*, Journal of Drug Targeting, vol.270, issue.5, pp.391-396, 1994.
DOI : 10.1111/j.1939-1676.1992.tb00339.x

I. Kurzman, H. Cheng, and E. Macewen, Effect of Liposome-Muramyl Tripeptide Combined with Recombinant Canine Granulocyte Colony-Stimulating Factor on Canine Monocyte Activity, Cancer Biotherapy, vol.9, issue.2, pp.113-121, 1994.
DOI : 10.1089/cbr.1994.9.113

B. Smith, I. Kurzman, and K. Schultz, Cytostatic Activity of Canine Plastic-Adherent Mononuclear Cells Against Canine Osteosarcoma Cells, Cancer Biotherapy, vol.8, issue.2, pp.137-144, 1993.
DOI : 10.1089/cbr.1993.8.137

E. Macewen, I. Kurzman, and R. Rosenthal, Therapy for Osteosarcoma in Dogs With Intravenous Injection of Liposome-Encapsulated Muramyl Tripeptide, JNCI Journal of the National Cancer Institute, vol.81, issue.12, pp.935-938, 1989.
DOI : 10.1093/jnci/81.12.935

E. Macewen, An Immunologic Approach to the Treatment of Cancer, Veterinary Clinics of North America, vol.7, issue.1, pp.65-75, 1977.
DOI : 10.1016/S0091-0279(77)50006-8

K. Mori, K. Ando, and D. Heymann, Liposomal muramyl tripeptide phosphatidyl ethanolamine: a safe and effective agent against osteosarcoma pulmonary metastases, Expert Review of Anticancer Therapy, vol.8, issue.2, pp.151-159, 2008.
DOI : 10.1586/14737140.8.2.151

K. Ando, K. Mori, and N. Corradini, Mifamurtide for the treatment of nonmetastatic osteosarcoma, Expert Opinion on Pharmacotherapy, vol.50, issue.1, pp.285-292, 2011.
DOI : 10.1007/BF01741788

URL : https://hal.archives-ouvertes.fr/inserm-00667530

P. Meyers, C. Schwartz, and M. Krailo, Osteosarcoma: The Addition of Muramyl Tripeptide to Chemotherapy Improves Overall Survival???A Report From the Children's Oncology Group, Journal of Clinical Oncology, vol.26, issue.4, pp.633-638, 2008.
DOI : 10.1200/JCO.2008.14.0095

P. Meyers, C. Schwartz, and M. Krailo, Osteosarcoma: A Randomized, Prospective Trial of the Addition of Ifosfamide and/or Muramyl Tripeptide to Cisplatin, Doxorubicin, and High-Dose Methotrexate, Journal of Clinical Oncology, vol.23, issue.9, pp.2004-2011, 2005.
DOI : 10.1200/JCO.2005.06.031

L. Kager, U. Pötschger, and S. Bielack, Review of mifamurtide in the treatment of patients with osteosarcoma, Therapeutics and Clinical Risk Management, vol.6, pp.279-286, 2010.
DOI : 10.2147/TCRM.S5688

J. Cook and T. Hagemann, Tumour-associated macrophages and cancer, Current Opinion in Pharmacology, vol.13, issue.4, pp.595-601, 2013.
DOI : 10.1016/j.coph.2013.05.017

E. Kleinerman, A. Raymond, and C. Bucana, Unique histological changes in lung metastases of osteosarcoma patients following therapy with liposomal muramyl tripeptide (CGP 19835A lipid), Cancer Immunology Immunotherapy, vol.66, issue.A
DOI : 10.1007/BF01741788

E. Kleinerman, J. Gano, and D. Johnston, Efficacy of Liposomal Muramyl Tripeptide (CGP 19835A) in the Treatment of Relapsed Osteosarcoma, American Journal of Clinical Oncology, vol.18, issue.2, pp.93-99, 1995.
DOI : 10.1097/00000421-199504000-00001

E. Buddingh, M. Kuijjer, and R. Duim, Tumor-Infiltrating 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.
DOI : 10.1158/1078-0432.CCR-10-2047

A. Ségaliny, A. Mohamadi, and B. Dizier, Interleukin-34 promotes tumor progression and metastatic process in osteosarcoma through induction of angiogenesis and macrophage recruitment, International Journal of Cancer, vol.1, issue.Suppl3
DOI : 10.1002/ijc.29376

A. Chou, E. Kleinerman, and M. Krailo, Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma, Cancer, vol.39, issue.22, pp.5339-5348, 2009.
DOI : 10.1002/cncr.24566

R. Barouch-bentov and K. Sauer, Mechanisms of drug resistance in kinases, Expert Opinion on Investigational Drugs, vol.7, issue.4, pp.153-208, 2011.
DOI : 10.1016/j.bmcl.2007.01.048

M. Serra, M. Pasello, and M. Manara, May P-glycoprotein status be used to stratify high-grade osteosarcoma patients? Results from the Italian/Scandinavian Sarcoma Group 1 treatment protocol, International Journal of Oncology, vol.29, pp.1459-1468, 2006.
DOI : 10.3892/ijo.29.6.1459

J. Pahl, K. Kwappenberg, and E. Varypataki, Macrophages inhibit human osteosarcoma cell growth after activation with the bacterial cell wall derivative liposomal muramyl tripeptide in combination with interferon-??, Journal of Experimental & Clinical Cancer Research, vol.33, issue.1, p.27, 2014.
DOI : 10.1126/science.1198443

J. Heiner, F. Miraldi, and S. Kallick, Localization of GD2-specific monoclonal antibody 3F8 in human osteosarcoma, Cancer Res, vol.47, pp.5377-5381, 1987.

A. Yu, M. Uttenreuther-fischer, and C. 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.
DOI : 10.1200/JCO.1998.16.6.2169

H. Shibuya, K. Hamamura, and H. Hotta, Enhancement of malignant properties of human osteosarcoma cells with disialyl gangliosides GD2/GD3, Cancer Science, vol.378, issue.Suppl 1, pp.1656-1664, 2012.
DOI : 10.1111/j.1349-7006.2012.02344.x

V. Poon, M. Roth, and S. Piperdi, Ganglioside GD2 expression is maintained upon recurrence in patients with osteosarcoma, Clinical Sarcoma Research, vol.5, issue.1, p.4, 2015.
DOI : 10.1073/pnas.1302825110

M. Roth, M. Linkowski, and J. Tarim, Ganglioside GD2 as a therapeutic target for antibody-mediated therapy in patients with osteosarcoma, Cancer, vol.4, issue.4, pp.548-554, 2014.
DOI : 10.1002/cncr.28461

B. Liu, Y. Wu, and Y. Zhou, Endothelin A Receptor Antagonism Enhances Inhibitory Effects of Anti-Ganglioside GD2 Monoclonal Antibody on Invasiveness and Viability of Human Osteosarcoma Cells, PLoS ONE, vol.142, issue.4, p.93576, 2014.
DOI : 10.1371/journal.pone.0093576.g008

J. Hamanishi, M. Mandai, and N. Matsumura, PD-1/PD-L1 blockade in cancer treatment: perspectives and issues, International Journal of Clinical Oncology, vol.331, issue.3, pp.456-461, 2016.
DOI : 10.1007/s10147-016-0959-z

J. Shen, G. Cote, and E. Choy, Programmed Cell Death Ligand 1 Expression in Osteosarcoma, Cancer Immunology Research, vol.2, issue.7, pp.690-698, 2014.
DOI : 10.1158/2326-6066.CIR-13-0224

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082476

T. Nowicki, J. Anderson, and N. Federman, Prospective immunotherapies in childhood sarcomas: PD1/PDL1 blockade in combination with tumor vaccines, Pediatric Research, vol.46, issue.3, pp.371-377, 2016.
DOI : 10.1097/CJI.0b013e31821ca6ce

T. Tsukahara, M. Emori, and K. Murata, The future of immunotherapy for sarcoma, Expert Opinion on Biological Therapy, vol.137, issue.9, pp.1-9, 2016.
DOI : 10.1038/nrc3322

M. Mandai, J. Hamanishi, and K. Abiko, Dual Faces of IFN?? in Cancer Progression: A Role of PD-L1 Induction in the Determination of Pro- and Antitumor Immunity, Clinical Cancer Research, vol.22, issue.10, pp.2329-2334, 2016.
DOI : 10.1158/1078-0432.CCR-16-0224

L. Festino, G. Botti, and P. Lorigan, Cancer Treatment with Anti-PD-1/PD-L1 Agents: Is PD-L1 Expression a Biomarker for Patient Selection?, Drugs, vol.2, issue.Suppl 3, pp.925-945, 2016.
DOI : 10.1111/pcmr.12340

J. Constantino, C. Gomes, and A. Falcão, Antitumor dendritic cell???based vaccines: lessons from 20??years of clinical trials and future perspectives, Translational Research, vol.168, pp.74-95, 2016.
DOI : 10.1016/j.trsl.2015.07.008

C. Chauvin, J. Philippeau, and C. Hémont, Killer Dendritic Cells Link Innate and Adaptive Immunity against Established Osteosarcoma in Rats, Cancer Research, vol.68, issue.22, pp.9433-9440109, 2008.
DOI : 10.1158/0008-5472.CAN-08-0104

D. Krishnadas, S. Shusterman, and F. Bai, A phase I trial combining decitabine/dendritic cell vaccine targeting MAGE-A1, MAGE-A3 and NY-ESO-1 for children with relapsed or therapy-refractory neuroblastoma and sarcoma, Cancer Immunology, Immunotherapy, vol.18, issue.23, pp.1251-1260, 2015.
DOI : 10.1007/s00262-015-1731-3

N. Himoudi, R. Wallace, and K. Parsley, Lack of T-cell responses following autologous tumour lysate pulsed dendritic cell vaccination, in patients with relapsed osteosarcoma, Clinical and Translational Oncology, vol.39, issue.4, pp.271-279, 2012.
DOI : 10.1007/s12094-012-0795-1

B. Allen, Systemic Targeted Alpha Radiotherapy for Cancer - A Review, Bangladesh Journal of Medical Physics, vol.6, issue.1, pp.67-80, 2013.
DOI : 10.3329/bjmp.v6i1.19755

P. Anderson, V. Subbiah, and E. Rohren, Bone-Seeking Radiopharmaceuticals as Targeted Agents of Osteosarcoma: Samarium-153-EDTMP and Radium-223, Adv Exp Med Biol, vol.804, pp.291-304, 2014.
DOI : 10.1007/978-3-319-04843-7_16

G. Henriksen, D. Fisher, and J. Roeske, Targeting of osseous sites with alpha-emitting 223 Ra: comparison with the beta-emitter 89 Sr in mice, J Nucl Med, vol.44, pp.252-259, 2003.

S. Nilsson, R. Larsen, and S. Fosså, First Clinical Experience with ??-Emitting Radium-223 in the Treatment of Skeletal Metastases, Clinical Cancer Research, vol.11, issue.12, pp.4451-4459, 2005.
DOI : 10.1158/1078-0432.CCR-04-2244

O. Sartor, R. Coleman, and S. Nilsson, Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial, The Lancet Oncology, vol.15, issue.7, pp.738-746, 2014.
DOI : 10.1016/S1470-2045(14)70183-4

D. Mortensen, S. Perrin-ninkovic, and G. Shevlin, Optimization of a Series of Triazole Containing Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors and the Discovery of CC-115, Journal of Medicinal Chemistry, vol.58, issue.14, pp.5599-5608, 2015.
DOI : 10.1021/acs.jmedchem.5b00627

J. Goodwin and K. Knidsen, Beyond DNA Repair: DNA-PK Function in Cancer, Cancer Discovery, vol.4, issue.10, pp.1126-1139, 2014.
DOI : 10.1158/2159-8290.CD-14-0358

D. Mortensen, K. Fultz, and W. Xu, 459 Preclinical characterization of CC-115, a novel inhibitor of DNA-PK and mTOR kinase currently under clinical investigation, European Journal of Cancer, vol.50, issue.6, p.50, 2014.
DOI : 10.1016/S0959-8049(14)70585-4

X. Li, J. Tian, and Q. Bo, Targeting DNA-PKcs increased anticancer drug sensitivity by suppressing DNA damage repair in osteosarcoma cell line MG63, Tumor Biology, vol.19, issue.12, pp.9365-9372, 2015.
DOI : 10.1007/s13277-015-3642-5

C. Sherr, D. Beach, and G. Shapiro, Targeting CDK4 and CDK6: From Discovery to Therapy, Cancer Discovery, vol.6, issue.4, pp.353-367, 2016.
DOI : 10.1158/2159-8290.CD-15-0894

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821753

L. Zhou, F. Liu, and Y. Li, Gpnmb/osteoactivin, an attractive target in cancer immunotherapy, Neoplasma, vol.59, issue.01, pp.1-5, 2012.
DOI : 10.4149/neo_2012_001

M. Roth, D. Barris, and S. Piperdi, Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma, Pediatric Blood & Cancer, vol.33, issue.1, pp.32-38, 2016.
DOI : 10.1002/pbc.25688

N. Bertrand, J. Wu, and X. Xu, Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology, Advanced Drug Delivery Reviews, vol.66, pp.2-25, 2014.
DOI : 10.1016/j.addr.2013.11.009

L. Wagner, H. Yin, and D. Eaves, Preclinical evaluation of nanoparticle albumin-bound paclitaxel for treatment of pediatric bone sarcoma, Pediatric Blood & Cancer, vol.19, issue.11, pp.2096-2098, 2014.
DOI : 10.1002/pbc.25062

M. Kang, J. Wang, and M. Makena, Activity of MM-398, Nanoliposomal Irinotecan (nal-IRI), in Ewing's Family Tumor Xenografts Is Associated with High Exposure of Tumor to Drug and High SLFN11 Expression, Clinical Cancer Research, vol.21, issue.5, pp.1139-1150, 2015.
DOI : 10.1158/1078-0432.CCR-14-1882

S. Mcgovern and A. Mahajan, Progress in Radiotherapy for Pediatric Sarcomas, Current Oncology Reports, vol.102, issue.4, pp.320-326, 2012.
DOI : 10.1007/s11912-012-0235-y

A. Matsunobu, R. Imai, and T. Kamada, Impact of carbon ion radiotherapy for unresectable osteosarcoma of the trunk, Cancer, vol.95, issue.18, pp.4555-4563, 2012.
DOI : 10.1002/cncr.27451

W. Zhang, M. Tanaka, and Y. Sugimoto, Carbon-ion radiotherapy of spinal osteosarcoma with long-term follow, European Spine Journal, vol.7, issue.Suppl 1, pp.113-117, 2016.
DOI : 10.1007/s00586-015-4202-9

M. Merchant, M. Wright, and K. Baird, Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors, Clinical Cancer Research, vol.22, issue.6, pp.1364-1370, 2016.
DOI : 10.1158/1078-0432.CCR-15-0491

J. Skoda, A. Nunukova, and T. Loja, Cancer stem cell markers in pediatric sarcomas: Sox2 is associated with tumorigenicity in immunodeficient mice, Tumor Biology, vol.25, issue.7, pp.9535-9548, 2016.
DOI : 10.1007/s13277-016-4837-0

G. Yan, Y. Lv, and Q. Guo, Advances in osteosarcoma stem cell research and opportunities for novel therapeutic targets, Cancer Letters, vol.370, issue.2, pp.268-274, 2016.
DOI : 10.1016/j.canlet.2015.11.003

S. Martins-neves, W. Corver, and D. Paiva-oliveira, Osteosarcoma Stem Cells Have Active Wnt/??-catenin and Overexpress SOX2 and KLF4, Journal of Cellular Physiology, vol.12, issue.4, pp.876-886, 2016.
DOI : 10.1002/jcp.25179

A. Satelli, A. Mitra, and J. Cutrera, Universal Marker and Detection Tool for Human Sarcoma Circulating Tumor Cells, Cancer Research, vol.74, issue.6, pp.1645-150, 2014.
DOI : 10.1158/0008-5472.CAN-13-1739

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959622

L. Chang, G. Asatrian, and S. Dry, Circulating tumor cells in sarcomas: a brief review, Medical Oncology, vol.7, issue.3, p.430, 2015.
DOI : 10.1007/s12032-014-0430-9

T. Gabriel, M. , R. Calleja, L. Chalopin, and A. , Circulating Tumor Cells: A Review of Non-EpCAM-Based Approaches for Cell Enrichment and Isolation, Clinical Chemistry, vol.62, issue.4, pp.571-581, 2016.
DOI : 10.1373/clinchem.2015.249706

URL : https://hal.archives-ouvertes.fr/inserm-01466107

C. Bolognesi, C. Forcato, and G. Buson, Digital Sorting of Pure Cell Populations Enables Unambiguous Genetic Analysis of Heterogeneous Formalin-Fixed Paraffin-Embedded Tumors by Next Generation Sequencing, Scientific Reports, vol.27, issue.1, p.20944, 2016.
DOI : 10.1093/bioinformatics/btq635