Biology of Bone Sarcomas and New Therapeutic Developments

1.

Stiller CA, Craft AW, Corazziari I (2001) Survival of children with bone sarcoma in Europe since 1978: results from the EUROCARE study. Eur J Cancer 37:760–766. https://doi.org/10.1016/S0959-8049(01)00004-1 PubMedCrossRef

2.

The ESMO/European Sarcoma Network Working Group (2012) Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23:vii100–vii109. https://doi.org/10.1093/annonc/mds254

3.

Heymann D (2014) Bone cancer: primary bone cancer an bone metastases, 2nd edn. Elsevier, San Diego

4.

Heymann D, Redini F (2011) Bone sarcomas: pathogenesis and new therapeutic approaches. IBMS BoneKEy 8:402–414. https://doi.org/10.1138/20110531 CrossRef

5.

Deschaseaux F, Sensébé L, Heymann D (2009) Mechanisms of bone repair and regeneration. Trends Mol Med 15:417–429. https://doi.org/10.1016/j.molmed.2009.07.002 PubMedCrossRef

6.

Panaroni C, Tzeng YS, Saeed H, Wu JY (2014) Mesenchymal progenitors and the osteoblast lineage in bone marrow hematopoietic niches. Curr Osteoporos Rep 12:22–32. https://doi.org/10.1007/s11914-014-0190-7 PubMedPubMedCentralCrossRef

7.

Garg P, Mazur MM, Buck AC, Wandtke ME, Liu J, Ebraheim NA (2017) Prospective review of mesenchymal stem cells differentiation into osteoblasts. Orthop Surg 9:13–19. https://doi.org/10.1111/os.12304 PubMedCrossRef

8.

Mohseny AB, Hogendoorn PC (2011) Concise review: mesenchymal tumors: when stem cells go mad. Stem Cells 29:397–403. https://doi.org/10.1002/stem.596 PubMedCrossRef

9.

Wagner ER, Luther G, Zhu G, Luo Q, Shi Q, Kim SH, Gao JL, Huang E, Gao Y, Yang K, Wang L, Teven C, Luo X, Liu X, Li M, Hu N, Su Y, Bi Y, He BC, Tang N, Luo J, Chen L, Zuo G, Rames R, Haydon RC, Luu HH, He TC (2011) Defective osteogenic differentiation in the development of osteosarcoma. Sarcoma 2011:325238. https://doi.org/10.1155/2011/325238 PubMedPubMedCentral

10.

Mohseny AB, Szuhai K, Romeo S, Buddingh EP, Briaire-de Bruijn I, de Jong D, van Pel M, Cleton-Jansen AM, Hogendoorn PC (2009) Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol 219:294–305. https://doi.org/10.1002/path.2603 PubMedCrossRef

11.

Tang X, Lu X, Guo W, Ren T, Zhao H, Zhao F, Tang G (2010) Different expression of Sox9 and Runx2 between chondrosarcoma and dedifferentiated chondrosarcoma cell line. Eur J Cancer Prev 19:466–471. https://doi.org/10.1097/CEJ.0b013e32833d942f PubMedCrossRef

12.

de Andrea CE, Reijnders CM, Kroon HM, de Jong D, Hogendoorn PC, Szuhai K, Bovée JV (2012) Secondary peripheral chondrosarcoma evolving from osteochondroma as a result of outgrowth of cells with functional EXT. Oncogene 31:1095–1104. https://doi.org/10.1038/onc.2011.311 PubMedCrossRef

13.

Zuntini M, Pedrini E, Parra A, Sgariglia F, Gentile FV, Pandolfi M, Alberghini M, Sangiorgi L (2010) Genetic models of osteochondroma onset and neoplastic progression: evidence for mechanisms alternative to EXT genes inactivation. Oncogene 29:3827–3834. https://doi.org/10.1038/onc.2010.135 PubMedCrossRef

14.

Musso N, Caronia FP, Castorina S, Lo Monte AI, Barresi V, Condorelli DF (2015) Somatic loss of an EXT2 gene mutation during malignant progression in a patient with hereditary multiple osteochondromas. Cancer Genet 208:62–67. https://doi.org/10.1016/j.cancergen.2015.01.002 PubMedCrossRef

15.

The Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, Ambros PF, Sheer D, Turc-Carel C, Triche TJ, Aurias A, Thomas G. Ewing family of tumors—a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 331:294–299. https://doi.org/10.1056/NEJM199408043310503

16.

Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O (2007) Mesenchymal stem cell features of Ewing tumors. Cancer Cell 11:421–429. https://doi.org/10.1016/j.ccr.2007.02.027 PubMedCrossRef

17.

von Levetzow C, Jiang X, Gwye Y, von Levetzow G, Hung L, Cooper A, Hsu JH, Lawlor ER (2011) Modeling initiation of Ewing sarcoma in human neural crest cells. PLoS ONE 6:e19305. https://doi.org/10.1371/journal.pone.0019305 CrossRef

18.

Tanaka M, Yamazaki Y, Kanno Y, Igarashi K, Aisaki K, Kanno J, Nakamura T (2014) Ewing’s sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors. J Clin Investig 124:3061–3074. https://doi.org/10.1172/JCI72399 PubMedPubMedCentralCrossRef

19.

Riggi N, Cironi L, Provero P, Suva ML, Kaloulis K, Garcia-Echeverria C, Hoffmann F, Trumpp A, Stamenkovic I (2005) Development of Ewing’s sarcoma from primary bone marrow-derived mesenchymal progenitor cells. Cancer Res 65:11459–11468. https://doi.org/10.1158/0008-5472.CAN-05-1696 PubMedCrossRef

20.

Uluçkan Ö, Segaliny A, Botter S, Santiago JM, Mutsaers AJ (2015) Preclinical mouse models of osteosarcoma. BoneKEy Rep 4:670. https://doi.org/10.1038/bonekey.2015.37 PubMedPubMedCentralCrossRef

21.

Botter SM, Arlt MJE, Fuchs B (2015) Mammalian models of bone sarcomas. In: Heymann D (ed) Bone cancer, second edition, chapter 30. Elsevier, San Diego, pp 349–364. https://doi.org/10.1016/B978-0-12-416721-6.00030-3

22.

Cleton-Jansen AM, (2015) Zebrafish models for studying bone cancers: mutants, transgenic fish and embryos. In: Heymann D (ed) Bone cancer, second edition, chapter 31. Elsevier, San Diego, pp 365–370. https://doi.org/10.1016/B978-0-12-416721-6.00031-5

23.

Walkley CR (2015) Modeling osteosarcoma: in vitro and in vivo approaches. In: Heymann D (ed) Bone cancer, second edition, chapter 17. Elsevier, San Diego, pp 195–204. https://doi.org/10.1016/B978-0-12-416721-6.00017-0

24.

Hoffman RM (2015) Patient-derived orthotopic xenografts: better mimic of metastasis than subcutaneous xenografts. Nat Rev Cancer 15:451–452. https://doi.org/10.1038/nrc3972 PubMedCrossRef

25.

Sampson VB, Kamara DF, Kolb EA (2013) Xenograft and genetically engineered mouse model systems of osteosarcoma and Ewing’s sarcoma: tumor models for cancer drug discovery. Expert Opin Drug Discov 8:1181–1189. https://doi.org/10.1517/17460441.2013.817988 PubMedPubMedCentralCrossRef

26.

Swarm RL, Correa JN, Andrews JR, Miller E (1964) Morphologic demonstration of recurrent tumor following X irradiation. Histologic study of irradiated murine chondrosarcoma transplants. J Natl Cancer Inst 33:657–672PubMed

27.

van Oosterwijk JG, Plass JR, Meijer D, Que I, Karperien M, Bovée JV (2015) An orthotopic mouse model for chondrosarcoma of bone provides an in vivo tool for drug testing. Virchows Arch 466:101–109. https://doi.org/10.1007/s00428-014-1670-y PubMedCrossRef

28.

Monderer D, Luseau A, Bellec A, David E, Ponsolle S, Saiagh S, Bercegeay S, Piloquet P, Denis MG, Lodé L, Rédini F, Biger M, Heymann D, Heymann MF, Le Bot R, Gouin F, Blanchard F (2013) New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance. Lab Invest 93:1100–1114. https://doi.org/10.1038/labinvest.2013.101 PubMedCrossRef

29.

Brown HK, Tellez-Gabriel M, Heymann D (2017) Cancer stem cells in osteosarcoma. Cancer Lett 386:189–195. https://doi.org/10.1016/j.canlet.2016.11.019 PubMedCrossRef

30.

Bousquet M, Noirot C, Accadbled F, Sales de Gauzy J, Castex MP, Brousset P, Gomez-Brouchet A (2016) Whole-exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations. Ann Oncol 27:738–744. https://doi.org/10.1093/annonc/mdw009 PubMedCrossRef

31.

Kovac M, Blattmann C, Ribi S, Smida J, Mueller NS, Engert F, Castro-Giner F, Weischenfeldt J, Kovacova M, Krieg A, Andreou D, Tunn PU, Dürr HR, Rechl H, Schaser KD, Melcher I, Burdach S, Kulozik A, Specht K, Heinimann K, Fulda S, Bielack S, Jundt G, Tomlinson I, Korbel JO, Nathrath M, Baumhoer D (2015) Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency. Nat Commun 6:8940. https://doi.org/10.1038/ncomms9940 PubMedPubMedCentralCrossRef

32.

Kresse SH, Rydbeck H, Skårn M, Namløs HM, Barragan-Polania AH, Cleton-Jansen AM, Serra M, Liestøl K, Hogendoorn PC, Hovig E, Myklebost O, Meza-Zepeda LA (2012) Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma. PLoS ONE 7:e48262. https://doi.org/10.1371/journal.pone.0048262 PubMedPubMedCentralCrossRef

33.

Balamuth NJ, Womer RB (2010) Ewing’s sarcoma. Lancet Oncol 11:184–192. https://doi.org/10.1016/S1470-2045(09)70286-4 PubMedCrossRef

34.

Burdach S, Jurgens H (2002) High-dose chemoradiotherapy (HDC) in the Ewing family of tumors (EFT). Crit Rev Oncol Hematol 41:169–189. https://doi.org/10.1016/S1040-8428(01)00154-8 PubMedCrossRef

35.

Iwamoto Y (2007) Diagnosis and treatment of Ewing’s sarcoma. Jpn J Clin Oncol 37:79–89. https://doi.org/10.1093/jjco/hyl142 PubMedCrossRef

36.

Llombart-Bosch A, Machado I, Navarro S, Bertoni F, Bacchini P, Alberghini M, Karzeladze A, Savelov N, Petrov S, Alvarado-Cabrero I, Mihaila D, Terrier P, Lopez-Guerrero JA, Picci P (2009) Histological heterogeneity of Ewing’s sarcoma/PNET: an immunohistochemical analysis of 415 genetically confirmed cases with clinical support. Virchows Arch 455:397–411. https://doi.org/10.1007/s00428-009-0842-7 PubMedCrossRef

37.

Zhang N, Liu H, Yue G, Zhang Y, You J, Wang H (2016) Molecular heterogeneity of Ewing sarcoma as detected by ion torrent sequencing. PLoS ONE 11(4):e0153546. https://doi.org/10.1371/journal.pone.0153546 PubMedPubMedCentralCrossRef

38.

Bühnemann C, Li S, Yu H, Branford White H, Schäfer KL, Llombart-Bosch A, Machado I, Picci P, Hogendoorn PC, Athanasou NA, Noble JA, Hassan AB (2014) Quantification of the heterogeneity of prognostic cellular biomarkers in Ewing sarcoma using automated image and random survival forest analysis. PLoS ONE 9:e107105. https://doi.org/10.1371/journal.pone.0107105 PubMedPubMedCentralCrossRef

39.

Sheffield NC, Pierron G, Klughammer J, Datlinger P, Schönegger A, Schuster M, Hadler J, Surdez D, Guillemot D, Lapouble E, Freneaux P, Champigneulle J, Bouvier R, Walder D, Ambros IM, Hutter C, Sorz E, Amaral AT, de Álava E, Schallmoser K, Strunk D, Rinner B, Liegl-Atzwanger B, Huppertz B, Leithner A, de Pinieux G, Terrier P, Laurence V, Michon J, Ladenstein R, Holter W, Windhager R, Dirksen U, Ambros PF, Delattre O, Kovar H, Bock C, Tomazou EM (2017) DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma. Nat Med 23:386–395. https://doi.org/10.1038/nm.4273 PubMedCrossRef

40.

Franzetti GA, Laud-Duval K, van der Ent W, Brisac A, Irondelle M, Aubert S, Dirksen U, Bouvier C, de Pinieux G, Snaar-Jagalska E, Chavrier P, Delattre O (2017) Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells. Oncogene 36:3505–3514. https://doi.org/10.1038/onc.2016.498 PubMedPubMedCentralCrossRef

41.

Brohl AS, Solomon DA, Chang W, Wang J, Song Y, Sindiri S, Patidar R, Hurd L, Chen L, Shern JF, Liao H, Wen X, Gerard J, Kim JS, Lopez Guerrero JA, Machado I, Wai DH, Picci P, Triche T, Horvai AE, Miettinen M, Wei JS, Catchpool D, Llombart-Bosch A, Waldman T, Khan J (2014) The genomic landscape of the Ewing sarcoma family of tumors reveals recurrent STAG2 mutation. PLoS Genet 10:e1004475. https://doi.org/10.1371/journal.pgen.1004475 PubMedPubMedCentralCrossRef

42.

Huang HY, Illei PB, Zhao Z, Mazumdar M, Huvos AG, Healey JH, Wexler LH, Gorlick R, Meyers P, Ladanyi M (2005) Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse. J Clin Oncol 23:548–558. https://doi.org/10.1200/JCO.2005.02.081 PubMedCrossRef

43.

Bovée JV, Cleton-Jansen AM, Taminiau AH, Hogendoorn PC (2005) Emerging pathways in the development of chondrosarcoma of bone and implications for targeted treatment. Lancet Oncol 6:599–607. https://doi.org/10.1016/S1470-2045(05)70282-5 PubMedCrossRef

44.

Bovée JV, Hogendoorn PC, Wunder JS, Alman BA (2010) Cartilage tumours and bone development: molecular pathology and possible therapeutic targets. Nat Rev Cancer 10:481–488. https://doi.org/10.1038/nrc2869 PubMedCrossRef

45.

Bovée JV, Hogendoorn PC, Wunder JS, Alman BA (2010) Cartilage tumours and bone development: molecular pathology and possible therapeutic targets. Nat Rev Cancer 10:481–488. https://doi.org/10.1038/nrc2869 PubMedCrossRef

46.

Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F (2013) Who classification of tumours of soft tissue and bone, fourth edition, IARC Ed. ISBN-13 9789283224341$4

47.

Speetjens FM, de Jong Y, Gelderblom H, Bovée JV (2016) Molecular oncogenesis of chondrosarcoma: impact for targeted treatment. Curr Opin Oncol 28:314–322. https://doi.org/10.1097/CCO.0000000000000300 PubMedCrossRef

48.

O’Neal LW, Ackerman LV (1952) Chondrosarcoma of bone. Cancer 5:551–577. https://doi.org/10.1002/1097-0142(195205)5:3<551::AID-CNCR2820050317>3.0.CO;2-Z PubMedCrossRef

49.

Meijer D, de Jong D, Pansuriya TC, van den Akker BE, Picci P, Szuhai K, Bovée JV (2012) Genetic characterization of mesenchymal, clear cell, and dedifferentiated chondrosarcoma. Genes Chromosoms Cancer 51(10):899–909. https://doi.org/10.1002/gcc.21974 CrossRef

50.

Amary MF, Bacsi K, Maggiani F, Damato S, Halai D, Berisha F, Pollock R, O’Donnell P, Grigoriadis A, Diss T, Eskandarpour M, Presneau N, Hogendoorn PC, Futreal A, Tirabosco R, Flanagan AM (2011) IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J Pathol 224:334–343. https://doi.org/10.1002/path.2913 PubMedCrossRef

51.

Tarpey PS, Behjati S, Cooke SL, Van Loo P, Wedge DC, Pillay N, Marshall J, O’Meara S, Davies H, Nik-Zainal S, Beare D, Butler A, Gamble J, Hardy C, Hinton J, Jia MM, Jayakumar A, Jones D, Latimer C, Maddison M, Martin S, McLaren S, Menzies A, Mudie L, Raine K, Teague JW, Tubio JM, Halai D, Tirabosco R, Amary F, Campbell PJ, Stratton MR, Flanagan AM, Futreal PA (2013) Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma. Nat Genet 45:923–926. https://doi.org/10.1038/ng.2668 PubMedPubMedCentralCrossRef

52.

Ottaviani G, Jaffe N (2009) The etiology of osteosarcoma. Cancer Treat Res 152:15–32. https://doi.org/10.1007/978-1-4419-0284-9_2 PubMedCrossRef

53.

Fiorenza F, Abudu A, Grimer RJ, Carter SR, Tillman RM, Ayoub K, Mangham DC, Davies AM (2002) Risk factors for survival and local control in chondrosarcoma of bone. J Bone Joint Surg Br 84:93–99. https://doi.org/10.1302/0301-620X.84B1.11942 PubMedCrossRef

54.

Wang ZQ, Ovitt C, Grigoriadis AE, Möhle-Steinlein U, Rüther U, Wagner EF (1992) Bone and haematopoietic defects in mice lacking c-fos. Nature 360(6406):741–745. https://doi.org/10.1038/360741a0 PubMedCrossRef

55.

Wang ZQ, Liang J, Schellander K, Wagner EF, Grigoriadis AE (1995) c-fos-induced osteosarcoma formation in transgenic mice: cooperativity with c-jun and the role of endogenous c-fos. Cancer Res 55:6244–62451PubMed

56.

Correa H (2016) Li-Fraumeni syndrome. J Pediatr Genet 5:84–88. https://doi.org/10.1055/s-0036-1579759 PubMedPubMedCentralCrossRef

57.

Simon T, Kohlhase J, Wilhelm C, Kochanek M, De Carolis B, Berthold F (2010) Multiple malignant diseases in a patient with Rothmund-Thomson syndrome with RECQL4 mutations: case report and literature review. Am J Med Genet A 152A:1575–1579. https://doi.org/10.1002/ajmg.a.33427 PubMed

58.

Murata K, Hatamochi A, Shinkai H, Ishikawa Y, Kawaguchi N, Goto M (1999) A case of Werner’s syndrome associated with osteosarcoma. J Dermatol 26:682–686. https://doi.org/10.1111/j.1346-8138.1999.tb02072.x PubMedCrossRef

59.

Lu L, Jin W, Liu H, Wang LL (2014) RECQ helicases and osteosarcoma. Adv Exp Med Biol 804:129–145. https://doi.org/10.1007/978-3-319-04843-7_7 PubMedCrossRef

60.

Ng AJ, Walia MK, Smeets MF, Mutsaers AJ, Sims NA, Purton LE, Walsh NC, Martin TJ, Walkley CR (2015) The DNA helicase recql4 is required for normal osteoblast expansion and osteosarcoma formation. PLoS Genet 11(4):e1005160. https://doi.org/10.1371/journal.pgen.1005160 PubMedPubMedCentralCrossRef

61.

Ren W, Gu G (2017) Prognostic implications of RB1 tumour suppressor gene alterations in the clinical outcome of human osteosarcoma: a meta-analysis. Eur J Cancer Care 26. https://doi.org/10.1111/ecc.12401

62.

Beltrami G, Ristori G, Scoccianti G, Tamburini A, Capanna R (2016) Hereditary Multiple Exostoses: a review of clinical appearance and metabolic pattern. Clin Cases Miner Bone Metab 13(2):110–118. https://doi.org/10.11138/ccmbm/2016.13.2.110 PubMedPubMedCentral

63.

Czajka CM, DiCaprio MR (2015) What is the proportion of patients with multiple hereditary exostoses who undergo malignant degeneration? Clin Orthop Relat Res 473:2355–2361. https://doi.org/10.1007/s11999-015-4134-z PubMedPubMedCentralCrossRef

64.

Alfranca A, Martinez-Cruzado L, Tornin J, Abarrategi A, Amaral T, de Alava E, Menendez P, Garcia-Castro J, Rodriguez R (2015) Bone microenvironment signals in osteosarcoma development. Cell Mol Life Sci 72:3097–3113. https://doi.org/10.1007/s00018-015-1918-y PubMedCrossRef

65.

Simard FA, Richert I, Vandermoeten A, Decouvelaere AV, Michot JP, Caux C, Blay JY, Dutour A (2016) Description of the immune microenvironment of chondrosarcoma and contribution to progression. Oncoimmunology 6:e1265716. https://doi.org/10.1080/2162402X.2016.1265716 PubMedPubMedCentralCrossRef

66.

David E, Blanchard F, Heymann MF, De Pinieux G, Gouin F, Rédini F, Heymann D (2011) The bone niche of chondrosarcoma: a sanctuary for drug resistance, tumour growth and also a source of new therapeutic targets. Sarcoma 2011:932451. https://doi.org/10.1155/2011/932451 PubMedPubMedCentralCrossRef

67.

Bailey KM, Airik M, Krook MA, Pedersen EA, Lawlor ER (2016) Micro-Environmental stress induces Src-dependent activation of invadopodia and cell migration in Ewing sarcoma. Neoplasia 18:480–488. https://doi.org/10.1016/j.neo.2016.06.008 PubMedPubMedCentralCrossRef

68.

Lissat A, Joerschke M, Shinde DA, Braunschweig T, Meier A, Makowska A, Bortnick R, Henneke P, Herget G, Gorr TA, Kontny U (2015) IL6 secreted by Ewing sarcoma tumor microenvironment confers anti-apoptotic and cell-disseminating paracrine responses in Ewing sarcoma cells. BMC Cancer 15:552. https://doi.org/10.1186/s12885-015-1564-7 PubMedPubMedCentralCrossRef

69.

Paget S. The distribution of secondary growths in cancer of the breast. Lancet 133:571–573. https://doi.org/10.1016/S0140-6736(00)49915-0

70.

Wittrant Y, Théoleyre S, Chipoy C, Padrines M, Blanchard F, Heymann D, Rédini F (2004) RANKL/RANK/OPG: new therapeutic targets in bone tumours and associated osteolysis. Biochim Biophys Acta 1704:49–57. https://doi.org/10.1016/j.bbcan.2004.05.002 PubMed

71.

Odri GA, Dumoucel S, Picarda G, Battaglia S, Lamoureux F, Corradini N, Rousseau J, Tirode F, Laud K, Delattre O, Gouin F, Heymann D, Redini F (2010) Zoledronic acid as a new adjuvant therapeutic strategy for Ewing’s sarcoma patients. Cancer Res 70:7610–7619. https://doi.org/10.1158/0008-5472.CAN-09-4272 PubMedCrossRef

72.

Moriceau G, Ory B, Mitrofan L, Riganti C, Blanchard F, Brion R, Charrier C, Battaglia S, Pilet P, Denis MG, Shultz LD, Mönkkönen J, Rédini F, Heymann D (2010) Zoledronic acid potentiates mTOR inhibition and abolishes the resistance of osteosarcoma cells to RAD001 (Everolimus): pivotal role of the prenylation process. Cancer Res 70:10329–10339. https://doi.org/10.1158/0008-5472.CAN-10-0578 PubMedPubMedCentralCrossRef

73.

Moriceau G, Ory B, Gobin B, Verrecchia F, Gouin F, Blanchard F, Redini F, Heymann D (2010) Therapeutic approach of primary bone tumours by bisphosphonates. Curr Pharm Des 16:2981–2987. https://doi.org/10.2174/138161210793563554 PubMedCrossRef

74.

Ohba T, Cole HA, Cates JM, Slosky DA, Haro H, Ando T, Schwartz HS, Schoenecker JG (2014) Bisphosphonates inhibit osteosarcoma-mediated osteolysis via attenuation of tumor expression of MCP-1 and RANKL. J Bone Miner Res 29:1431–1445. https://doi.org/10.1002/jbmr.2182 PubMedCrossRef

75.

Lamoureux F, Richard P, Wittrant Y, Battaglia S, Pilet P, Trichet V, Blanchard F, Gouin F, Pitard B, Heymann D, Redini F (2007) Therapeutic relevance of osteoprotegerin gene therapy in osteosarcoma: blockade of the vicious cycle between tumor cell proliferation and bone resorption. Cancer Res 67:7308–7318. https://doi.org/10.1158/0008-5472.CAN-06-4130 PubMedCrossRef

76.

Gouin F, Ory B, Rédini F, Heymann D (2006) Zoledronic acid slows down rat primary chondrosarcoma development, recurrent tumor progression after intralesional curretage and increases overall survival. Int J Cancer 119:980–984. https://doi.org/10.1002/ijc.21951 PubMedCrossRef

77.

Ory B, Blanchard F, Battaglia S, Gouin F, Rédini F, Heymann D (2007) 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. Mol Pharmacol 71:333–343. https://doi.org/10.1124/mol.106.028837 PubMedCrossRef

78.

Endo-Munoz L, Cumming A, Rickwood D, Wilson D, Cueva C, Ng C, Strutton G, Cassady AI, Evdokiou A, Sommerville S, Dickinson I, Guminski A, Saunders NA (2010) Loss of osteoclasts contributes to development of osteosarcoma pulmonary metastases. Cancer Res 70:7063–7072. https://doi.org/10.1158/0008-5472.CAN-09-4291 PubMedCrossRef

79.

Cackowski FC, Anderson JL, Patrene KD, Choksi RJ, Shapiro SD, Windle JJ, Blair HC, Roodman GD (2010) Osteoclasts are important for bone angiogenesis. Blood 115:140–149. https://doi.org/10.1182/blood-2009-08-237628 PubMedPubMedCentralCrossRef

80.

Endo-Munoz L, Evdokiou A, Saunders NA (2012) The role of osteoclasts and tumour-associated macrophages in osteosarcoma metastasis. Biochim Biophys Acta 1826:434–442. https://doi.org/10.1016/j.bbcan.2012.07.00 PubMed

81.

Perrot P, Rousseau J, Bouffaut AL, Rédini F, Cassagnau E, Deschaseaux F, Heymann MF, Heymann D, Duteille F, Trichet V, Gouin F (2010) Safety concern between autologous fat graft, mesenchymal stem cell and osteosarcoma recurrence. PLoS ONE 5(6):e10999. https://doi.org/10.1371/journal.pone.0010999 PubMedPubMedCentralCrossRef

82.

Cortini M, Massa A, Avnet S, Bonuccelli G, Baldini N (2016) Tumor-Activated Mesenchymal stromal cells promote osteosarcoma stemness and migratory potential via IL-6 secretion. PLoS ONE 11:e0166500. https://doi.org/10.1371/journal.pone.0166500 PubMedPubMedCentralCrossRef

83.

Massa A, Perut F, Chano T, Woloszyk A, Mitsiadis TA, Avnet S, Baldini N (2017) The effect of extracellular acidosis on the behaviour of mesenchymal stem cells in vitro. Eur Cell Mater 33:252–267. https://doi.org/10.22203/eCM.v033a19 PubMedCrossRef

84.

Avnet S, Di Pompo G, Chano T, Errani C, Ibrahim-Hashim A, Gillies RJ, Donati DM, Baldini N (2017) Cancer-associated mesenchymal stroma fosters the stemness of osteosarcoma cells in response to intratumoral acidosis via NF-κB activation. Int J Cancer 140(6):1331–1345. https://doi.org/10.1002/ijc.30540 PubMedCrossRef

85.

Tellez-Gabriel M, Charrier C, Brounais-Le Royer B, Mullard M, Brown HK, Verrecchia F, Heymann D (2017) Analysis of gap junctional intercellular communications using a dielectrophoresis-based microchip. Eur J Cell Biol 96:110–118. https://doi.org/10.1016/j.ejcb.2017.01.003 PubMedCrossRef

86.

Xu H, Gu S, Riquelme MA, Burra S, Callaway D, Cheng H, Guda T, Schmitz J, Fajardo RJ, Werner SL, Zhao H, Shang P, Johnson ML, Bonewald LF, Jiang JX (2015) Connexin 43 channels are essential for normal bone structure and osteocyte viability. J Bone Miner Res 30:436–448. https://doi.org/10.1002/jbmr.2374 PubMedCrossRef

87.

Talbot J, Verrecchia F (2012) Gap junctions and bone remodeling. Biol Aujourdhui 206:125–134. https://doi.org/10.1051/jbio/2012016 PubMedCrossRef

88.

Plotkin LI, Davis HM, Cisterna BA, Sáez JC (2017) Connexins and pannexins in bone and skeletal muscle. Curr Osteoporos Rep 15:326–334. https://doi.org/10.1007/s11914-017-0374-z PubMedCrossRef

89.

Talbot J, Brion R, Picarda G, Amiaud J, Chesneau J, Bougras G, Stresing V, Tirode F, Heymann D, Redini F, Verrecchia F (2013) Loss of connexin43 expression in Ewing’s sarcoma cells favors the development of the primary tumor and the associated bone osteolysis. Biochim Biophys Acta 1832:553–564. https://doi.org/10.1016/j.bbadis.2013.01.001 PubMedCrossRef

90.

Torreggiani E, Roncuzzi L, Perut F, Zini N, Baldini N (2016) Multimodal transfer of MDR by exosomes in human osteosarcoma. Int J Oncol 49:189–196. https://doi.org/10.3892/ijo.2016.3509 PubMedCrossRef

91.

Baglio SR, Lagerweij T, Pérez-Lanzón M, Ho XD, Léveillé N, Melo SA, Cleton-Jansen AM, Jordanova ES, Roncuzzi L, Greco M, van Eijndhoven MAJ, Grisendi G, Dominici M, Bonafede R, Lougheed SM, de Gruijl TD, Zini N, Cervo S, Steffan A, Canzonieri V, Martson A, Maasalu K, Köks S, Wurdinger T, Baldini N, Pegtel DM (2017) Blocking tumor-educated MSC paracrine activity halts osteosarcoma progression. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-16-2726 (in press)PubMed

92.

Heymann D, Ory B, Blanchard F, Heymann MF, Coipeau P, Charrier C, Couillaud S, Thiery JP, Gouin F, Redini F (2005) Enhanced tumor regression and tissue repair when zoledronic acid is combined with ifosfamide in rat osteosarcoma. Bone 37:74–86. https://doi.org/10.1016/j.bone.2005.02.020 PubMedCrossRef

93.

Karsenty G, Oury F (2010) The central regulation of bone mass, the first link between bone remodeling and energy metabolism. J Clin Endocrinol Metab 95:4795–4801. https://doi.org/10.1210/jc.2010-1030 PubMedCrossRef

94.

Corr A, Smith J, Baldock P (2017) Neuronal control of bone remodeling. Toxicol Pathol. https://doi.org/10.1177/0192623317738708 PubMed

95.

Dimitri P, Rosen C (2017) The central nervous system and bone metabolism: an evolving story. Calcif Tissue Int 100:476–485. https://doi.org/10.1007/s00223-016-0179-6 PubMedCrossRef

96.

Kondo A, Mogi M, Koshihara Y, Togari A (2001) Signal transduction system for interleukin-6 and interleukin-11 synthesis stimulated by epinephrine in human osteoblasts and human osteogenic sarcoma cells. Biochem Pharmacol 61:319–326. https://doi.org/10.1016/S0006-2952(00)00544-X PubMedCrossRef

97.

Broadhead ML, Choong PF, Dass CR (2012) Efficacy of continuously administered PEDF-derived synthetic peptides against osteosarcoma growth and metastasis. J Biomed Biotechnol 2012:230298. https://doi.org/10.1155/2012/230298 PubMedPubMedCentralCrossRef

98.

Punzo F, Tortora C, Di Pinto D, Manzo I, Bellini G, Casale F, Rossi F (2017) Anti-proliferative, pro-apoptotic and anti-invasive effect of EC/EV system in human osteosarcoma. Oncotarget 8:54459–54471. https://doi.org/10.18632/oncotarget.17089 PubMedPubMedCentralCrossRef

99.

Otero JE, Stevens JW, Malandra AE, Fredericks DC, Odgren PR, Buckwalter JA, Morcuende J (2014) Osteoclast inhibition impairs chondrosarcoma growth and bone destruction. J Orthop Res 32:1562–1571. https://doi.org/10.1002/jor.22714 PubMedCrossRef

100.

Piperno-Neumann S, Le Deley MC, Rédini F, Pacquement H, Marec-Bérard P, Petit P, Brisse H, Lervat C, Gentet JC, Entz-Werlé N, Italiano A, Corradini N, Bompas E, Penel N, Tabone MD, Gomez-Brouchet A, Guinebretière JM, Mascard E, Gouin F, Chevance A, Bonnet N, Blay JY, Brugières L, Sarcoma Group of UNICANCER, French Society of Pediatric Oncology (SFCE), French Sarcoma Group (GSF-GETO) (2016) Zoledronate in combination with chemotherapy and surgery to treat osteosarcoma (OS2006): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 17:1070–1080. https://doi.org/10.1016/S1470-2045(16)30096-1 PubMedCrossRef

101.

Lézot F, Chesneau J, Navet B, Gobin B, Amiaud J, Choi Y, Yagita H, Castaneda B, Berdal A, Mueller CG, Rédini F, Heymann D (2015) Skeletal consequences of RANKL-blocking antibody (IK22–5) injections during growth: mouse strain disparities and synergic effect with zoledronic acid. Bone 73:51–59. https://doi.org/10.1016/j.bone.2014.12.011 PubMedCrossRef

102.

Qian BZ, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141:39–51. https://doi.org/10.1016/j.cell.2010.03.014 PubMedPubMedCentralCrossRef

103.

Sousa S, Auriola S, Mönkkönen J, Määttä J (2015) Liposome encapsulated zoledronate favours M1-like behaviour in murine macrophages cultured with soluble factors from breast cancer cells. BMC Cancer 15:4. https://doi.org/10.1186/s12885-015-1005-7 PubMedPubMedCentralCrossRef

104.

Veltman JD, Lambers ME, van Nimwegen M, Hendriks RW, Hoogsteden HC, Hegmans JP, Aerts JG (2010) Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma. Br J Cancer 103:629–641. https://doi.org/10.1038/sj.bjc.6605814 PubMedPubMedCentralCrossRef

105.

Buddingh EP, Kuijjer ML, Duim RA, Bürger H, Agelopoulos K, Myklebost O, Serra M, Mertens F, Hogendoorn PC, Lankester AC, Cleton-Jansen AM (2011) Tumor-infiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: a rationale for treatment with macrophage activating agents. Clin Cancer Res 17:2110–2119. https://doi.org/10.1158/1078-0432.CCR-10-2047 PubMedCrossRef

106.

Dumars C, Ngyuen JM, Gaultier A, Lanel R, Corradini N, Gouin F, Heymann D, Heymann MF (2016) Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma. Oncotarget 7:78343–78354. https://doi.org/10.18632/oncotarget.13055 PubMedPubMedCentralCrossRef

107.

Fujiwara T, Fukushi J, Yamamoto S, Matsumoto Y, Setsu N, Oda Y, Yamada H, Okada S, Watari K, Ono M, Kuwano M, Kamura S, Iida K, Okada Y, Koga M, Iwamoto Y (2011) Macrophage infiltration predicts a poor prognosis for human Ewing sarcoma. Am J Pathol 179:1157–1170. https://doi.org/10.1016/j.ajpath.2011.05.03 PubMedPubMedCentralCrossRef

108.

Inagaki Y, Hookway E, Williams KA, Hassan AB, Oppermann U, Tanaka Y, Soilleux E, Athanasou NA (2016) Dendritic and mast cell involvement in the inflammatory response to primary malignant bone tumours. Clin Sarcoma Res 6:13. https://doi.org/10.1186/s13569-016-0053-3 PubMedPubMedCentralCrossRef

109.

Heymann MF, Lezot F, Heymann D. The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma. Cellular Immunol. https://doi.org/10.1016/j.cellimm.2017.10.011 (in press)

110.

Théoleyre S, Mori K, Cherrier B, Passuti N, Gouin F, Rédini F, Heymann D (2005) Phenotypic and functional analysis of lymphocytes infiltrating osteolytic tumors: use as a possible therapeutic approach of osteosarcoma. BMC Cancer 5:123. https://doi.org/10.1186/1471-2407-5-123 PubMedPubMedCentralCrossRef

111.

Meftah M, Schult P, Henshaw RM (2013) Long-term results of intralesional curettage and cryosurgery for treatment of low-grade chondrosarcoma. J Bone Joint Surg Am 95:1358–1364. https://doi.org/10.2106/JBJS.L.00442 PubMedCrossRef

112.

Riedel RF, Larrier N, Dodd L, Kirsch D, Martinez S, Brigman BE (2009) The clinical management of chondrosarcoma. Curr Treat Options Oncol 10:94–106. https://doi.org/10.1007/s11864-009-0088-2 PubMedCrossRef

113.

Heymann MF, Brown HK, Heymann D (2016) Drugs in early clinical development for the treatment of osteosarcoma. Expert Opin Investig Drugs 25:1265–1280. https://doi.org/10.1080/13543784.2016.1237503 PubMedCrossRef

114.

Meyers PA, Schwartz CL, Krailo MD, Healey JH, Bernstein ML, Betcher D, Ferguson WS, Gebhardt MC, Goorin AM, Harris M, Kleinerman E, Link MP, Nadel H, Nieder M, Siegal GP, Weiner MA, Wells RJ, Womer RB, Grier HE. Children’s Oncology Group (2008) Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival–a report from the Children’s Oncology Group. J Clin Oncol 26:633–638. https://doi.org/10.1200/JCO.2008.14.0095 PubMedCrossRef

115.

Redini F, Odri GA, Picarda G, Gaspar N, Heymann MF, Corradini N, Heymann D (2013) Drugs targeting the bone microenvironment: new therapeutic tools in Ewing’s sarcoma? Expert Opin Emerg Drugs 18:339–352. https://doi.org/10.1517/14728214.2013.823948 PubMedCrossRef

116.

Gaspar N, Hawkins DS, Dirksen U, Lewis IJ, Ferrari S, Le Deley MC, Kovar H, Grimer R, Whelan J, Claude L, Delattre O, Paulussen M, Picci P, Sundby Hall K, van den Berg H, Ladenstein R, Michon J, Hjorth L, Judson I, Luksch R, Bernstein ML, Marec-Bérard P, Brennan B, Craft AW, Womer RB, Juergens H, Oberlin O (2015) Ewing sarcoma: current management and future approaches through collaboration. J Clin Oncol 33:3036–3046. https://doi.org/10.1200/JCO.2014.59.5256 PubMedCrossRef

117.

Xing M, Yan F, Yu S, Shen P (2015) Efficacy and cardiotoxicity of liposomal doxorubicin-based chemotherapy in advanced breast cancer: a meta-analysis of ten randomized trials. PLoS ONE 10:e0133569. https://doi.org/10.1371/journal.pone.0133569 PubMedPubMedCentralCrossRef

118.

Kang MH, Wang J, Makena MR, Lee JS, Paz N, Hall CP, Song MM, Calderon RI, Cruz RE, Hindle A, Ko W, Fitzgerald JB, Drummond DC, Triche TJ, Reynolds CP (2015) 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. Clin Cancer Res 21:1139–1150. https://doi.org/10.1158/1078-0432.CCR-14-1882 PubMedCrossRef

119.

Mitchison TJ (2012) The proliferation rate paradox in antimitotic chemotherapy. Mol Biol Cell 23:1–6. https://doi.org/10.1091/mbc.E10-04-0335 PubMedPubMedCentralCrossRef

120.

Ségaliny AI, Tellez-Gabriel M, Heymann MF, Heymann D (2015) Receptor tyrosine kinases: characterisation, mechanism of action and therapeutic interests for bone cancers. J Bone Oncol 4:1–12. https://doi.org/10.1016/j.jbo.2015.01.001 PubMedPubMedCentralCrossRef

121.

Heymann D, Rédini F (2013) Targeted therapies for bone sarcomas. BoneKEy Rep 2:378. https://doi.org/10.1038/bonekey.2013.112 PubMedPubMedCentralCrossRef

122.

Safwat A, Boysen A, Lücke A, Rossen P (2014) Pazopanib in metastatic osteosarcoma: significant clinical response in three consecutive patients. Acta Oncol 53:1451–1454. https://doi.org/10.3109/0284186X.2014.948062 PubMedCrossRef

123.

Attia S, Okuno SH, Robinson SI, Webber NP, Indelicato DJ, Jones RL, Bagaria SP, Jones RL, Sherman C, Kozak KR, Cortese CM, McFarland T, Trent JC, Maki RG (2015) Clinical activity of pazopanib in metastatic extraosseous Ewing sarcoma. Rare Tumors 7:5992. https://doi.org/10.4081/rt.2015.5992 PubMedPubMedCentralCrossRef

124.

Mross K, Frost A, Steinbild S, Hedbom S, Büchert M, Fasol U, Unger C, Krätzschmar J, Heinig R, Boix O, Christensen O (2012) 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. Clin Cancer Res 18:2658–2667. https://doi.org/10.1158/1078-0432 PubMedCrossRef

125.

Subbiah V, Anderson P, Rohren E (2015) Alpha emitter radium 223 in high-risk osteosarcoma: first clinical evidence of response and blood-brain barrier penetration. JAMA Oncol 1:253–255. https://doi.org/10.1001/jamaoncol.2014.289 PubMedCrossRef

126.

Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A, Lau KW, Greninger P, Thompson IR, Luo X, Soares J, Liu Q, Iorio F, Surdez D, Chen L, Milano RJ, Bignell GR, Tam AT, Davies H, Stevenson JA, Barthorpe S, Lutz SR, Kogera F, Lawrence K, McLaren-Douglas A, Mitropoulos X, Mironenko T, Thi H, Richardson L, Zhou W, Jewitt F, Zhang T, O’Brien P, Boisvert JL, Price S, Hur W, Yang W, Deng X, Butler A, Choi HG, Chang JW, Baselga J, Stamenkovic I, Engelman JA, Sharma SV, Delattre O, Saez-Rodriguez J, Gray NS, Settleman J, Futreal PA, Haber DA, Stratton MR, Ramaswamy S, McDermott U, Benes CH (2012) Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 483:570–575. https://doi.org/10.1038/nature11005 PubMedPubMedCentralCrossRef

127.

Choy E, Butrynski JE, Harmon DC, Morgan JA, George S, Wagner AJ, D’Adamo D, Cote GM, Flamand Y, Benes CH, Haber DA, Baselga JM, Demetri GD (2014) Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy. BMC Cancer 4:813. https://doi.org/10.1186/1471-2407-14-813 CrossRef

128.

van Maldegem AM, Bovée JV, Peterse EF, Hogendoorn PC, Gelderblom H (2016) Ewing sarcoma: the clinical relevance of the insulin-like growth factor 1 and the poly-ADP-ribose-polymerase pathway. Eur J Cancer 53:171–180. https://doi.org/10.1016/j.ejca.2015.09.009 PubMedCrossRef

129.

Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, Iyer AK (2017) PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol 8:561. https://doi.org/10.3389/fphar.2017.00561 PubMedPubMedCentralCrossRef

130.

Pinto N, Park JR, Murphy E, Yearley J, McClanahan T, Annamalai L, Hawkins DS, Rudzinski ER (2017) Patterns of PD-1, PD-L1, and PD-L2 expression in pediatric solid tumors. Pediatr Blood Cancer. https://doi.org/10.1002/pbc.26613

131.

Paydas S, Bagir EK, Deveci MA, Gonlusen G (2016) Clinical and prognostic significance of PD-1 and PD-L1 expression in sarcomas. Med Oncol 33:93. https://doi.org/10.1007/s12032-016-0807-z PubMedCrossRef

132.

Shen JK, Cote GM, Choy E, Yang P, Harmon D, Schwab J, Nielsen GP, Chebib I, Ferrone S, Wang X, Wang Y, Mankin H, Hornicek FJ, Duan Z (2014) Programmed cell death ligand 1 expression in osteosarcoma. Cancer Immunol Res 2:690–698. https://doi.org/10.1158/2326-6066.CIR-13-0224 PubMedPubMedCentralCrossRef

133.

Sundara YT, Kostine M, Cleven AH, Bovée JV, Schilham MW, Cleton-Jansen AM (2017) Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: a rationale for T-cell-based immunotherapy. Cancer Immunol Immunother 66:119–128. https://doi.org/10.1007/s00262-016-1925-3 PubMedCrossRef

134.

Paoluzzi L, Cacavio A, Ghesani M, Karambelkar A, Rapkiewicz A, Weber J, Rosen G (2016) Response to anti-PD1 therapy with nivolumab in metastatic sarcomas. Clin Sarcoma Res 6:24. https://doi.org/10.1186/s13569-016-0064-0 PubMedPubMedCentralCrossRef

135.

Dobrenkov K, Ostrovnaya I, Gu J, Cheung IY, Cheung NK (2016) Oncotargets GD2 and GD3 are highly expressed in sarcomas of children, adolescents, and young adults. Pediatr Blood Cancer 63:1780–1785. https://doi.org/10.1002/pbc.26097 PubMedPubMedCentralCrossRef

136.

Bernstein-Molho R, Kollender Y, Issakov J, Bickels J, Dadia S, Flusser G, Meller I, Sagi-Eisenberg R, Merimsky O (2012) Clinical activity of mTOR inhibition in combination with cyclophosphamide in the treatment of recurrent unresectable chondrosarcomas. Cancer Chemother Pharmacol 70:855–860. https://doi.org/10.1007/s00280-012-1968-x PubMedCrossRef

137.

Perez J, Decouvelaere AV, Pointecouteau T, Pissaloux D, Michot JP, Besse A, Blay JY, Dutour A (2012) Inhibition of chondrosarcoma growth by mTOR inhibitor in an in vivo syngeneic rat model. PLoS ONE 7:e32458. https://doi.org/10.1371/journal.pone.0032458 PubMedPubMedCentralCrossRef

138.

Kostine M, Cleven AH, de Miranda NF, Italiano A, Cleton-Jansen AM, Bovée JV (2016) Analysis of PD-L1, T-cell infiltrate and HLA expression in chondrosarcoma indicates potential for response to immunotherapy specifically in the dedifferentiated subtype. Mod Pathol 29:1028–1037. https://doi.org/10.1038/modpathol.2016.108 PubMedCrossRef

139.

Amelio JM, Rockberg J, Hernandez RK et al (2016) Population-based study of giant cell tumor of bone in Sweden (1983–2011). Cancer Epidemiol 42:82–89. https://doi.org/10.1016/j.canep.2016.03.014 PubMedCrossRef

140.

Dahlin DC, Cupps RE, Johnson EW Jr (1970) Giant-cell tumor: a study of 195 cases. Cancer 25:1061–1070. https://doi.org/10.1002/1097-0142(197005)25:5<1061::AID-CNCR2820250509>3.0.CO;2-E PubMedCrossRef

141.

Rosario M, Kim HS, Yun JY, Han I (2017) Surveillance for lung metastasis from giant cell tumor of bone. J Surg Oncol. https://doi.org/10.1002/jso.24739 (in press)PubMed

142.

Renema N, Navet B, Heymann MF, Lezot F, Heymann D (2016) RANK-RANKL signalling in cancer. Biosci Rep 36(4):e00366. https://doi.org/10.1042/BSR20160150 PubMedPubMedCentralCrossRef

143.

Gouin F, Rochwerger AR, Di Marco A, Rosset P, Bonnevialle P, Fiorenza F, Anract P (2014) Adjuvant treatment with zoledronic acid after extensive curettage for giant cell tumours of bone. Eur J Cancer 50:2425–2431. https://doi.org/10.1016/j.ejca.2014.06.003 PubMedCrossRef

144.

Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, Kroep J, Grimer R, Reichardt P, Rutkowski P, Schuetze S, Skubitz K, Staddon A, Thomas D, Qian Y, Jacobs (2013) Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol 14:901–908. https://doi.org/10.1016/S1470-2045(13)70277-8 PubMedCrossRef

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