title: Novel targets with potential therapeutic applications in osteosarcoma.
abstract: For patients with osteosarcoma, the development of metastases, often to the lungs, is the most common cause of death. Long-term outcomes for patients who present with localized or disseminated disease have largely remained unchanged over the past 20 years. Further improvements in outcome are not likely to come from intensification of cytotoxic chemotherapy; as such, new targets for treatment are needed. A view toward such targets in osteosarcoma may be constructed based on three common clinical features of the disease. These include the origin of osteosarcoma in the bone or primitive mesenchymal cells, the predictable process of metastatic progression characterized by this disease, and the development of metastatic lesions almost exclusively in the lung. It is likely and potentially favorable for some targets to be relevant for more than one process. This review summarizes novel targets under evaluation for the treatment of osteosarcoma based on these three features of the disease.
authors.affiliation: National Institutes of Health, National Cancer Institute, Pediatric Oncology Branch, Tumor Metastasis Biology Section, 37 Convent Drive, Bethesda, MD 20892, USA. khannac@mail.nih.gov
authors.forename: Chand
authors.initials: C
authors.lastname: Khanna
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D006801:Humans; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents
references.citation: Life Sci. 2005 Mar 18;76(18):2091-101
references.pmid: 15826876
references.citation: Pediatr Blood Cancer. 2008 Jun;50(6):1190-7
references.pmid: 18260118
references.citation: Hematol Oncol Clin North Am. 2005 Jun;19(3):573-90, viii
references.pmid: 15939198
references.citation: Lancet. 2007 May 19;369(9574):1742-57
references.pmid: 17512859
references.citation: Clin Cancer Res. 2003 Nov 15;9(15):5442-53
references.pmid: 14654523
references.citation: Cancer. 2007 Mar 1;109(5):813-9
references.pmid: 17265525
references.citation: N Engl J Med. 1998 Aug 6;339(6):357-63
references.pmid: 9691101
references.citation: Curr Med Chem. 2007;14(20):2126-35
references.pmid: 17691952
references.citation: Expert Opin Investig Drugs. 2007 Sep;16(9):1459-65
references.pmid: 17714031
references.citation: Curr Med Chem. 2007;14(13):1381-7
references.pmid: 17584050
references.citation: Nat Rev Mol Cell Biol. 2003 Dec;4(12):915-25
references.pmid: 14685170
references.citation: J Clin Oncol. 2008 Feb 1;26(4):633-8
references.pmid: 18235123
references.citation: Expert Rev Anticancer Ther. 2006 Jul;6(7):1075-85
references.pmid: 16831079
references.citation: Nat Med. 2004 Feb;10(2):182-6
references.pmid: 14704791
references.citation: Clin Cancer Res. 2007 Nov 1;13(21):6247-51
references.pmid: 17975134
references.citation: Cancer Res. 2008 Mar 15;68(6):1935-44
references.pmid: 18339875
references.citation: J Clin Oncol. 1998 Nov;16(11):3641-8
references.pmid: 9817286
references.citation: Crit Rev Oncol Hematol. 2007 Dec;64(3):198-207
references.pmid: 17855108
references.citation: Curr Pharm Des. 2004;10(21):2577-92
references.pmid: 15320746
references.citation: Clin Cancer Res. 2002 Jul;8(7):2406-12
references.pmid: 12114446
references.citation: Nat Rev Drug Discov. 2007 Sep;6(9):734-45
references.pmid: 17690708
references.citation: Endocr Rev. 2007 Feb;28(1):20-47
references.pmid: 16931767
references.citation: Curr Pharm Biotechnol. 2008 Feb;9(1):2-8
references.pmid: 18289051
references.citation: Clin Cancer Res. 2006 Dec 15;12(24):7444-55
references.pmid: 17189418
references.citation: Histol Histopathol. 2004 Oct;19(4):1325-44
references.pmid: 15375775
references.citation: J Pediatr Surg. 2007 Jan;42(1):1-11
references.pmid: 17208533
references.citation: Curr Oncol Rep. 2007 Jul;9(4):316-22
references.pmid: 17588357
references.citation: Int J Radiat Oncol Biol Phys. 2007 May 1;68(1):211-7
references.pmid: 17448875
references.citation: Curr Opin Oncol. 2007 Jul;19(4):341-6
references.pmid: 17545797
references.citation: Pediatr Blood Cancer. 2008 Mar;50(3):581-7
references.pmid: 17457854
references.citation: J Cell Biochem. 2007 Dec 1;102(5):1095-102
references.pmid: 17955492
references.citation: Cancer Metastasis Rev. 2006 Dec;25(4):541-9
references.pmid: 17180711
references.citation: Cancer Res. 2004 Mar 15;64(6):2047-53
references.pmid: 15026342
references.citation: Cancer Res. 2007 Mar 15;67(6):2800-8
references.pmid: 17363602
references.citation: Med Hypotheses. 2008;70(2):281-6
references.pmid: 17683874
references.citation: Exp Cell Res. 2003 Nov 1;290(2):370-80
references.pmid: 14567994
references.citation: Biochem J. 2008 Mar 15;410(3):439-53
references.pmid: 18290764
references.citation: Nat Med. 2001 Jun;7(6):673-9
references.pmid: 11385503
references.citation: Science. 2004 Jul 9;305(5681):200-5
references.pmid: 15247469
references.citation: Int J Cancer. 2005 Jan 10;113(2):179-88
references.pmid: 15455381
references.citation: J Clin Oncol. 2005 Mar 20;23(9):2004-11
references.pmid: 15774791
references.citation: Cancer Res. 2005 Mar 15;65(6):2406-11
references.pmid: 15781656
references.citation: J Med Chem. 2007 Feb 22;50(4):603-6
references.pmid: 17256836
references.citation: Oncogene. 2008 Jan 24;27(5):684-93
references.pmid: 17684486
references.citation: Nat Rev Cancer. 2008 Feb;8(2):147-56
references.pmid: 18202698
references.citation: Cancer Cell Int. 2007 Sep 10;7:14
references.pmid: 17845729
references.citation: Clin Cancer Res. 2005 Jul 1;11(13):4666-73
references.pmid: 16000559
references.citation: Ann N Y Acad Sci. 2007 Oct;1113:202-16
references.pmid: 17513464
references.citation: Endocr Dev. 2005;9:11-16
references.pmid: 15879684
references.citation: Int J Oncol. 2006 Nov;29(5):1053-64
references.pmid: 17016635
references.citation: Clin Cancer Res. 2007 Mar 15;13(6):1625-9
references.pmid: 17363512
references.citation: Am J Pathol. 1996 Oct;149(4):1209-19
references.pmid: 8863670
references.citation: Genes Chromosomes Cancer. 2005 Feb;42(2):158-63
references.pmid: 15540165
references.citation: Eur J Cancer. 2004 Sep;40(14):2013-5
references.pmid: 15341972
references.citation: J Clin Invest. 2002 Jun;109(12):1607-15
references.pmid: 12070308
references.citation: Clin Exp Metastasis. 2003;20(5):421-30
references.pmid: 14524531
references.citation: Cancer Invest. 2007 Dec;25(8):785-94
references.pmid: 18058475
references.citation: Stem Cells Dev. 2007 Feb;16(1):7-23
references.pmid: 17348802
references.citation: Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3263-70
references.pmid: 18089720
references.citation: Clin Exp Metastasis. 2008;25(3):201-11
references.pmid: 18071913
references.citation: Carcinogenesis. 2004 Dec;25(12):2293-301
references.pmid: 15347599
references.citation: Cancer Lett. 2005 Jul 8;225(1):1-26
references.pmid: 15922853
references.citation: Cancer Genet Cytogenet. 2007 Nov;179(1):52-61
references.pmid: 17981215
references.citation: Nature. 2005 Dec 15;438(7070):967-74
references.pmid: 16355214
references.citation: J Cell Physiol. 2007 Nov;213(2):316-25
references.pmid: 17607709
references.citation: Pediatr Blood Cancer. 2008 May;50(5):976-82
references.pmid: 18213710
references.citation: Eur J Cancer. 1997 Oct;33(11):1725-31
references.pmid: 9470825
references.citation: Clin Cancer Res. 2007 Dec 15;13(24):7243-6
references.pmid: 18094402