Therapeutic targets for neuroblastomas

Expert Opinion on Therapeutic Targets

Volumn 18, Issue 3, 2014, Pages 277-292

  Brodeur, Garrett M ^a,b   Iyer, Radhika ^a   Croucher, Jamie L ^a   Zhuang, Tiangang ^a   Higashi, Mayumi ^a   Kolla, Venkatadri ^a  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

ARID1A B; ATRX; AURKA; BCL2; CAMTA1; CASZ1; CHD5; CHEK1 CHK1; FOXR1; GD2; HDAC; KIF1B ; MCL1; MYCN; NCAM; NET; Neuroblastoma; NTRK1 TrkA; NTRK2 TrkB; ODC; PTPN11; RAS; TP53 P53

Indexed keywords

ANIMALS; EPIGENESIS, GENETIC; GENE SILENCING; HUMANS; MUTATION; NERVOUS SYSTEM NEOPLASMS; NEUROBLASTOMA;

EID: 84893823680     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2014.867946     Document Type: Review

References (163)

1. Brodeur GM, Hogarty MD, Mosse YP, Maris JM. Neuroblastoma. In: Pizzo PA, Poplack DG, editors. Principles and practice of pediatric oncology. 6th edition. Lippincott, Williams and Wilkins; Philadelphia: 2011. p. 886-922
2. Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 2003;3(3): 203-16
3. Maris JM, Hogarty MD, Bagatell R, Cohn SL. Neuroblastoma. Lancet 2007;369(9579): 2106-20
4. Mosse YP, Greshock J, Margolin A, et al. High-resolution detection and mapping of genomic DNA alterations in neuroblastoma. Genes Chromosomes Cancer 2005;43(4): 390-403
5. Tomioka N, Oba S, Ohira M, et al. Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature. Oncogene 2008;27(4): 441-9
6. Schwab M, Alitalo K, Klempnauer KH, et al. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature 1983;305(5931): 245-8
7. Schwab M, Varmus HE, Bishop JM, et al. Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc. Nature 1984;308(5956): 288-91 • These two papers by Schwab et al. were the first descriptions of the MYCN protooncogene.
8. Brodeur GM, Seeger RC, Schwab M, et al. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 1984;224(4653): 1121-4 • This was the first desription of the clinical importance of MYCN oncogene activation by amplification in a human tumor.
9. Seeger RC, Brodeur GM, Sather H, et al. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med 1985;313(18): 1111-16 • This paper first described the correlation of MYCN amplification with survival in NB patients.
10. Bagatell R, Rumcheva P, London WB, et al. Outcomes of children with intermediate-risk neuroblastoma after treatment stratified by MYCN status and tumor cell ploidy. J Clin Oncol 2005;23(34): 8819-27
11. George RE, London WB, Cohn SL, et al. Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol 2005;23(27): 6466-73
12. Look AT, Hayes FA, Shuster JJ, et al. Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol 1991;9(4): 581-91
13. Schneiderman J, London WB, Brodeur GM, et al. Clinical significance of MYCN amplification and ploidy in favorable-stage neuroblastoma: a report from the Children's Oncology Group. J Clin Oncol 2008;26(6): 913-18
14. Pession A, Tonelli R. The MYCN oncogene as a specific and selective drug target for peripheral and central nervous system tumors. Curr Cancer Drug Targets 2005;5(4): 273-83
15. Bell E, Chen L, Liu T, et al. MYCN oncoprotein targets and their therapeutic potential. Cancer Lett 2010;293(2): 144-57
16. Pugh TJ, Morozova O, Attiyeh EF, et al. The genetic landscape of high-risk neuroblastoma. Nat Genet 2013;45(3): 279-84 • This paper described the prevalence of specific gene mutations in highrisk NBs.
17. Puissant A, Frumm SM, Alexe G, et al. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov 2013;3(3): 308-23 • This was the first paper to describe an inhibitor of MYCN expression to treat NBs.
18. Hogarty MD, Norris MD, Davis K, et al. ODC1 is a critical determinant of MYCN oncogenesis and a therapeutic target in neuroblastoma. Cancer Res 2008;68(23): 9735-45
19. Koomoa DL, Geerts D, Lange I, et al. DFMO/eflornithine inhibits migration and invasion downstream of MYCN and involves p27Kip1 activity in neuroblastoma. Int J Oncol 2013;42(4): 1219-28
20. Rounbehler RJ, Li W, Hall MA, et al. Targeting ornithine decarboxylase impairs development of MYCN-amplified neuroblastoma. Cancer Res 2009;69(2): 547-53
21. Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 1994;263(5151): 1281-4
22. Webb TR, Slavish J, George RE, et al. Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy. Expert Rev Anticancer Ther 2009;9(3): 331-56
23. Chen Y, Takita J, Choi YL, et al. Oncogenic mutations of ALK kinase in neuroblastoma. Nature 2008;455(7215): 971-4
24. George RE, Sanda T, Hanna M, et al. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 2008;455(7215): 975-8
25. Janoueix-Lerosey I, Lequin D, Brugieres L, et al. Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 2008;455(7215): 967-70
26. Mosse YP, Laudenslager M, Longo L, et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 2008;455(7215): 930-5 • The above four papers (Chen et al., George et al., Janoueix-Lerosey et al., Mosse et al.) were the simultaneous first description of ALK as the major hereditary NB predisposition gene.
27. Azarova AM, Gautam G, George RE. Emerging importance of ALK in neuroblastoma. Semin Cancer Biol 2011;21(4): 267-75
28. Carpenter EL, Mosse YP. Targeting ALK in neuroblastoma-preclinical and clinical advancements. Nat Rev Clin Oncol 2012;9(7): 391-9
29. Mosse YP, Lim MS, Voss SD, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol 2013;14(6): 472-80 • This was the first report of a clinical trial using the ALK inhibitor, crizotinib.
30. Berry T, Luther W, Bhatnagar N, et al. The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell 2012;22(1): 117-30
31. Bresler SC, Wood AC, Haglund EA, et al. Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma. Sci Transl Med 2011;3(108): 108ra14
32. Heuckmann JM, Holzel M, Sos ML, et al. ALK mutations conferring differential resistance to structurally diverse ALK inhibitors. Clin Cancer Res 2011;17(23): 7394-401
33. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 2001;24: 677-736
34. Skaper SD. The neurotrophin family of neurotrophic factors: an overview. Methods Mol Biol 2012;846: 1-12
35. Brodeur GM, Minturn JE, Ho R, et al. Trk receptor expression and inhibition in neuroblastomas. Clin Cancer Res 2009;15(10): 3244-50
36. Brodeur GM, Nakagawara A, Yamashiro DJ, et al. Expression of TrkA, TrkB and TrkC in human neuroblastomas. J Neurooncol 1997;31(1-2): 49-55
37. Kogner P, Barbany G, Dominici C, et al. Coexpression of messenger RNA for TRK protooncogene and low affinity nerve growth factor receptor in neuroblastoma with favorable prognosis. Cancer Res 1993;53(9): 2044-50
38. Nakagawara A, Arima M, Azar CG, et al. Inverse relationship between trk expression and N-myc amplification in human neuroblastomas. Cancer Res 1992;52(5): 1364-8 • This paper first reported the expression of TrkA/NTRK1 in NBs, and its inverse relationship with MYCN amplification.
39. Nakagawara A, Arima-Nakagawara M, Scavarda NJ, et al. Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma. N Engl J Med 1993;328(12): 847-54 • This paper, and papers by Suzuki et al. (1993) and Kogner et al. (1993) were the first description of the favorable prognostic impact of high TrkA/NTRK1 expression.
40. Nakagawara A, Azar CG, Scavarda NJ, Brodeur GM. Expression and function of TRK-B and BDNF in human neuroblastomas. Mol Cell Biol 1994;14(1): 759-67 • This paper was the first to describe the association of high TrkB/NTRK2 expression with MYCN amplification and with poor out come in NBs.
41. Ryden M, Sehgal R, Dominici C, et al. Expression of mRNA for the neurotrophin receptor trkC in neuroblastomas with favourable tumour stage and good prognosis. Br J Cancer 1996;74(5): 773-9
42. Suzuki T, Bogenmann E, Shimada H, et al. Lack of high-affinity nerve growth factor receptors in aggressive neuroblastomas. J Natl Cancer Inst 1993;85(5): 377-84
43. Thiele CJ, Li Z, McKee AE. On Trk-the TrkB signal transduction pathway is an increasingly important target in cancer biology. Clin Cancer Res 2009;15(19): 5962-7
44. Yamashiro DJ, Liu XG, Lee CP, et al. Expression and function of Trk-C in favourable human neuroblastomas. Eur J Cancer 1997;33(12): 2054-7
45. Yamashiro DJ, Nakagawara A, Ikegaki N, et al. Expression of TrkC in favorable human neuroblastomas. Oncogene 1996;12(1): 37-41
46. Fagan AM, Zhang H, Landis S, et al. TrkA, but not TrkC, receptors are essential for survival of sympathetic neurons in vivo. J Neurosci 1996;16(19): 6208-18
47. Tacconelli A, Farina AR, Cappabianca L, et al. TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma. Cancer Cell 2004;6(4): 347-60 • This was the first description of TrkAIII isoform expression in NBs.
48. Tacconelli A, Farina AR, Cappabianca L, et al. Alternative TrkAIII splicing: a potential regulated tumor-promoting switch and therapeutic target in neuroblastoma. Future Oncol 2005;1(5): 689-98
49. Acheson A, Conover JC, Fandl JP, et al. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature 1995;374(6521): 450-3
50. Ho R, Eggert A, Hishiki T, et al. Resistance to chemotherapy mediated by TrkB in neuroblastomas. Cancer Res 2002;62(22): 6462-6
51. Matsumoto K, Wada RK, Yamashiro JM, et al. Expression of brain-derived neurotrophic factor and p145TrkB affects survival, differentiation, and invasiveness of human neuroblastoma cells. Cancer Res 1995;55(8): 1798-806
52. Nakamura K, Martin KC, Jackson JK, et al. Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial growth factor expression via hypoxia-inducible factor-1alpha in neuroblastoma cells. Cancer Res 2006;66(8): 4249-55 • The above 4 papers by Acheson et al., Ho et al., Matsumoto et al., and Nakamura et al., describe the assocation of TrkB expression with aggressive behavior, such as invasion, metastasis, angiogenesis and drug resistance in NBs.
53. Evans AE, Kisselbach KD, Liu X, et al. Effect of CEP-751 (KT-6587) on neuroblastoma xenografts expressing TrkB. Med Pediatr Oncol 2001;36(1): 181-4
54. Evans AE, Kisselbach KD, Yamashiro DJ, et al. Antitumor activity of CEP-751 (KT-6587) on human neuroblastoma and medulloblastoma xenografts. Clin Cancer Res 1999;5(11): 3594-602 • These two papers by Evans et al., were the first preclinical description of the potential utility of a Trk inhibitor to treat NBs.
55. Iyer R, Evans AE, Qi X, et al. Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft models of neuroblastoma. Clin Cancer Res 2010;16(5): 1478-85
56. Iyer R, Varela CR, Minturn JE, et al. AZ64 inhibits TrkB and enhances the efficacy of chemotherapy and local radiation in neuroblastoma xenografts. Cancer Chemother Pharmacol 2012;70(3): 477-86
57. Minturn JE, Evans AE, Villablanca JG, et al. Phase I trial of lestaurtinib for children with refractory neuroblastoma: a new approaches to neuroblastoma therapy consortium study. Cancer Chemother Pharmacol 2011;68(4): 1057-65 • This Phase I clinical trial describes the efficacy of a TRK inhibitor to treat NB patients with recurrent/refractory NBs.
58. Zenker M. Genetic and pathogenetic aspects of Noonan syndrome and related disorders. Horm Res 2009;72(Suppl 2): 57-63
59. Grossmann KS, Rosario M, Birchmeier C, Birchmeier W. The tyrosine phosphatase Shp2 in development and cancer. Adv Cancer Res 2010;106: 53-89
60. Hasle H. Malignant diseases in Noonan syndrome and related disorders. Horm Res 2009;72(Suppl 2): 8-14
61. Myatt SS, Lam EW. The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer 2007;7(11): 847-59
62. Olanich ME, Barr FG. A call to ARMS: targeting the PAX3-FOXO1 gene in alveolar rhabdomyosarcoma. Expert Opin Ther Targets 2013;17(5): 607-23
63. Santo EE, Ebus ME, Koster J, et al. Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in neuroblastoma. Oncogene 2012;31(12): 1571-81 • This was the first description of a recurring translocation in NBs, involving the FOXR1 gene.
64. Molenaar JJ, Domingo-Fernandez R, Ebus ME, et al. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet 2012;44(11): 1199-206 • This paper described LIN28B as a potential oncogenic driver in NBs.
65. Islam A, Kageyama H, Takada N, et al. High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma. Oncogene 2000;19(5): 617-23
66. Lamers F, van der Ploeg I, Schild L, et al. Knockdown of survivin (BIRC5) causes apoptosis in neuroblastoma via mitotic catastrophe. Endocr Relat Cancer 2011;18(6): 657-68
67. Garcia I, Mayol G, Rios J, et al. A threegene expression signature model for risk stratification of patients with neuroblastoma. Clin Cancer Res 2012;18(7): 2012-23
68. Hailat N, Keim DR, Melhem RF, et al. High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification. J Clin Invest 1991;88(1): 341-5
69. Leone A, Seeger RC, Hong CM, et al. Evidence for nm23 RNA overexpression, DNA amplification and mutation in aggressive childhood neuroblastomas. Oncogene 1993;8(4): 855-65
70. Thompson PM, Gotoh T, Kok M, et al. CHD5, a new member of the chromodomain gene family, is preferentially expressed in the nervous system. Oncogene 2003;22(7): 1002-11 • This paper first described the cloning and characterization of CHD5 as a potential TSG in NBs.
71. Hall JA, Georgel PT. CHD proteins: a diverse family with strong ties. Biochem Cell Biol 2007;85(4): 463-76
72. Murawska M, Brehm A. CHD chromatin remodelers and the transcription cycle. Transcription 2011;2(6): 244-53
73. Fujita T, Igarashi J, Okawa ER, et al. CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas. J Natl Cancer Inst 2008;100(13): 940-9 • This report showed that CHD5 functions as a TSG in NBs.
74. Garcia I, Mayol G, Rodriguez E, et al. Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma. Mol Cancer 2010;9: 277
75. Koyama H, Zhuang T, Light JE, et al. Mechanisms of CHD5 Inactivation in neuroblastomas. Clin Cancer Res 2012;18(6): 1588-97 • These two papers by Garcia et al. (2010) and Koyama et al. (2012) show that CHD5 expression has prognostic significance in NBs.
76. Bagchi A, Papazoglu C, Wu Y, et al. CHD5 is a tumor suppressor at human 1p36. Cell 2007;128(3): 459-75 • This paper used chromosome engineering to show that CHD5 functioned as a TSG in a mouse model and potentially in other tumor types, like gliomas.
77. Mulero-Navarro S, Esteller M. Chromatin remodeling factor CHD5 is silenced by promoter CpG island hypermethylation in human cancer. Epigenetics 2008;3(4): 210-15
78. Wang J, Chen H, Fu S, et al. The involvement of CHD5 hypermethylation in laryngeal squamous cell carcinoma. Oral Oncol 2011;47(7): 601-8
79. Wang L, He S, Tu Y, et al. Downregulation of chromatin remodeling factor CHD5 is associated with a poor prognosis in human glioma. J Clin Neurosci 2013;20(7): 958-63
80. Wang X, Lau KK, So LK, Lam YW. CHD5 is down-regulated through promoter hypermethylation in gastric cancer. J Biomed Sci 2009;16: 95
81. Wong RR, Chan LK, Tsang TP, et al. CHD5 Downregulation Associated with Poor Prognosis in Epithelial Ovarian Cancer. Gynecol Obstet Invest 2011;72(3): 203-7
82. Zhao R, Yan Q, Lv J, et al. CHD5, a tumor suppressor that is epigenetically silenced in lung cancer. Lung Cancer 2012;76(3): 324-31
83. Henrich KO, Fischer M, Mertens D, et al. Reduced expression of CAMTA1 correlates with adverse outcome in neuroblastoma patients. Clin Cancer Res 2006;12(1): 131-8
84. Henrich KO, Bauer T, Schulte J, et al. CAMTA1, a 1p36 tumor suppressor candidate, inhibits growth and activates differentiation programs in neuroblastoma cells. Cancer Res 2011;71(8): 3142-51 • These two papers by Henrich et al. show that CAMTA1 is a potential TSG in NBs.
85. Cho WC. OncomiRs: the discovery and progress of microRNAs in cancers. Mol Cancer 2007;6: 60
86. Wang R, Ma J, Wu Q, et al. Functional role of miR-34 family in human cancer. Curr Drug Targets 2013;14(10): 1185-91
87. Cole KA, Attiyeh EF, Mosse YP, et al. A functional screen identifies miR-34a as a candidate neuroblastoma tumor suppressor gene. Mol Cancer Res 2008;6(5): 735-42
88. Wei JS, Song YK, Durinck S, et al. The MYCN oncogene is a direct target of miR-34a. Oncogene 2008;27(39): 5204-13
89. Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene 2007;26(34): 5017-22 • The above three papers by Cole et al., Wei et al., and Welch et al., were the first description of miR-34a as a potential TSG in NBs.
90. Tivnan A, Tracey L, Buckley PG, et al. MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma. BMC Cancer 2011;11: 33
91. Chen QR, Yu LR, Tsang P, et al. Systematic proteome analysis identifies transcription factor YY1 as a direct target of miR-34a. J Proteome Res 2011;10(2): 479-87
92. Ohira M, Kageyama H, Mihara M, et al. Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line. Oncogene 2000;19(37): 4302-7
93. Chen YZ, Soeda E, Yang HW, et al. Homozygous deletion in a neuroblastoma cell line defined by a high-density STS map spanning human chromosome band 1p36. Genes Chromosomes Cancer 2001;31(4): 326-32
94. Zhao C, Takita J, Tanaka Y, et al. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell 2001;105(5): 587-97
95. Schlisio S, Kenchappa RS, Vredeveld LC, et al. The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor. Genes Dev 2008;22(7): 884-93 • This paper first described KIF1Bb as a potential TSG in NBs.
96. Munirajan AK, Ando K, Mukai A, et al. KIF1Bbeta functions as a haploinsufficient tumor suppressor gene mapped to chromosome 1p36.2 by inducing apoptotic cell death. J Biol Chem 2008;283(36): 24426-34
97. Liu Z, Yang X, Tan F, et al. Molecular cloning and characterization of human Castor, a novel human gene upregulated during cell differentiation. Biochem Biophys Res Commun 2006;344(3): 834-44 • This paper first described CASZ1 as a potential TSG in NBs.
98. Liu Z, Naranjo A, Thiele CJ. CASZ1b, the short isoform of CASZ1 gene, coexpresses with CASZ1a during neurogenesis and suppresses neuroblastoma cell growth. PLoS One 2011;6(4):e18557
99. Liu Z, Yang X, Li Z, et al. CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression. Cell Death Differ 2011;18(7): 1174-83
100. Ho L, Crabtree GR. Chromatin remodelling during development. Nature 2010;463(7280): 474-84
101. Jones S, Wang TL, Shih Ie M, et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science 2010;330(6001): 228-31
102. Khursheed M, Kolla JN, Kotapalli V, et al. ARID1B, a member of the human SWI/SNF chromatin remodeling complex, exhibits tumour-suppressor activities in pancreatic cancer cell lines. Br J Cancer 2013;108(10): 2056-62
103. Sausen M, Leary RJ, Jones S, et al. Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nat Genet 2013;45(1): 12-17 • This paper was the first description of ARID1A and ARID1B mutations in NBs.
104. Attiyeh EF, London WB, Mosse YP, et al. Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med 2005;353(21): 2243-53
105. Guo C, White PS, Weiss MJ, et al. Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas. Oncogene 1999;18(35): 4948-57
106. Michels E, Hoebeeck J, De Preter K, et al. CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23. BMC Cancer 2008;8: 173
107. Nowacki S, Skowron M, Oberthuer A, et al. Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma. Oncogene 2008;27(23): 3329-38
108. Cheung NK, Zhang J, Lu C, et al. Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA 2012;307(10): 1062-71
109. Molenaar JJ, Koster J, Zwijnenburg DA, et al. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature 2012;483(7391): 589-93 • These papers by Cheung et al., and Molenaar et al., are the first description of mutations in the ATRX gene in older NB patients.
110. Sieber-Blum M, Ren Z. Norepinephrine transporter expression and function in noradrenergic cell differentiation. Mol Cell Biochem 2000;212(1-2): 61-70
111. Dubois SG, Geier E, Batra V, et al. Evaluation of norepinephrine transporter expression and metaiodobenzylguanidine avidity in neuroblastoma: a report from the Children's Oncology Group. Int J Mol Imaging 2012;2012: 250834
112. Howard JP, Maris JM, Kersun LS, et al. Tumor response and toxicity with multiple infusions of high dose 131IMIBG for refractory neuroblastoma. Pediatr Blood Cancer 2005;44(3): 232-9 • This report by Howard et al. shows that targeting the NET with radiolabeled MIBG is an important modality for the targeted radiotherapy of NBs.
113. Taggart D, Dubois S, Matthay KK. Radiolabeled metaiodobenzylguanidine for imaging and therapy of neuroblastoma. Q J Nucl Med Mol Imaging 2008;52(4): 403-18
114. Navid F, Santana VM, Barfield RC. Anti-GD2 antibody therapy for GD2- expressing tumors. Curr Cancer Drug Targets 2010;10(2): 200-9
115. Modak S, Cheung NK. Disialoganglioside directed immunotherapy of neuroblastoma. Cancer Invest 2007;25(1): 67-77
116. Yu AL, Uttenreuther-Fischer MM, Huang CS, et al. Phase I trial of a human-mouse chimeric antidisialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma. J Clin Oncol 1998;16(6): 2169-80
117. Yu AL, Gilman AL, Ozkaynak MF, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010;363(14): 1324-34 • This report demonstrated a significant prognostic advantage of immunotherapy with anti-GD2 antibody combined with GM-CSF and IL2 in patients with high-risk NB.
118. Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 2011;365(8): 725-33
119. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013;368(16): 1509-18 • The above two papers by Porter et al., and Grupp et al., show great promise for using modified T-cells for the targeted cellular immunotherapy of selected cancers.
120. Bozzi F, Gambirasio F, Luksch R, et al. Detecting CD56+/NB84+/CD45- immunophenotype in the bone marrow of patients with metastatic neuroblastoma using flow cytometry. Anticancer Res 2006;26(5A): 3281-7
121. Ferreira-Facio CS, Milito C, Botafogo V, et al. Contribution of multiparameter flow cytometry immunophenotyping to the diagnostic screening and classification of pediatric cancer. PLoS One 2013;8(3):e55534
122. Nagai J, Ishida Y, Koga N, et al. A new sensitive and specific combination of CD81/CD56/CD45 monoclonal antibodies for detecting circulating neuroblastoma cells in peripheral blood using flow cytometry. J Pediatr Hematol Oncol 2000;22(1): 20-6
123. Park SJ, Park CJ, Kim S, et al. Detection of bone marrow metastases of neuroblastoma with immunohistochemical staining of CD56, chromogranin A, and synaptophysin. Appl Immunohistochem Mol Morphol 2010;18(4): 348-52
124. Pashankar FD, O'Dorisio MS, Menda Y. MIBG and somatostatin receptor analogs in children: current concepts on diagnostic and therapeutic use. J Nucl Med 2005;46(Suppl 1): 55S-61S
125. O'Dorisio MS, Hauger M, Cecalupo AJ. Somatostatin receptors in neuroblastoma: diagnostic and therapeutic implications. Semin Oncol 1994;21(5 Suppl 13): 33-7 • This report summarizes the potential utility of targeting SSR's for the diagnosis and treatment of NBs.
126. O'Dorisio MS, Chen F, O'Dorisio TM, et al. Characterization of somatostatin receptors on human neuroblastoma tumors. Cell Growth Differ 1994;5(1): 1-8
127. Muller PA, Vousden KH. p53 mutations in cancer. Nat Cell Biol 2013;15(1): 2-8
128. Prabhu VV, Allen JE, Hong B, et al. Therapeutic targeting of the p53 pathway in cancer stem cells. Expert Opin Ther Targets 2012;16(12): 1161-74
129. Vogan K, Bernstein M, Leclerc JM, et al. Absence of p53 gene mutations in primary neuroblastomas. Cancer Res 1993;53(21): 5269-73
130. Hosoi G, Hara J, Okamura T, et al. Low frequency of the p53 gene mutations in neuroblastoma. Cancer 1994;73(12): 3087-93
131. Goldman SC, Chen CY, Lansing TJ, et al. The p53 signal transduction pathway is intact in human neuroblastoma despite cytoplasmic localization. Am J Pathol 1996;148(5): 1381-5
132. Tweddle DA, Pearson AD, Haber M, et al. The p53 pathway and its inactivation in neuroblastoma. Cancer Lett 2003;197(1-2): 93-8
133. Keshelava N, Zuo JJ, Chen P, et al. Loss of p53 function confers high-level multidrug resistance in neuroblastoma cell lines. Cancer Res 2001;61(16): 6185-93 • This resport suggests that loss of p53 function at relapse may be associated with a multidrug resistance phenotype in NBs.
134. Barbieri E, Mehta P, Chen Z, et al. MDM2 inhibition sensitizes neuroblastoma to chemotherapy-induced apoptotic cell death. Mol Cancer Ther 2006;5(9): 2358-65
135. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002;2(9): 647-56
136. Barille-Nion S, Bah N, Vequaud E, Juin P. Regulation of cancer cell survival by BCL2 family members upon prolonged mitotic arrest: opportunities for anticancer therapy. Anticancer Res 2012;32(10): 4225-33
137. Goldsmith KC, Hogarty MD. Targeting programmed cell death pathways with experimental therapeutics: opportunities in high-risk neuroblastoma. Cancer Lett 2005;228(1-2): 133-41
138. Lestini BJ, Goldsmith KC, Fluchel MN, et al. Mcl1 downregulation sensitizes neuroblastoma to cytotoxic chemotherapy and small molecule Bcl2-family antagonists. Cancer Biol Ther 2009;8(16): 1587-95 • These reports by Goldsmith et al., and Lestini et al., provide evidence that targeting apoptotic pathways may be a useful therapeutic strategy in NBs.
139. Ballas K, Lyons J, Janssen JW, Bartram CR. Incidence of ras gene mutations in neuroblastoma. Eur J Pediatr 1988;147(3): 313-14
140. Ireland CM. Activated N-ras oncogenes in human neuroblastoma. Cancer Res 1989;49(20): 5530-3
141. Moley JF, Brother MB, Wells SA, et al. Low frequency of ras gene mutations in neuroblastomas, pheochromocytomas, and medullary thyroid cancers. Cancer Res 1991;51(6): 1596-9
142. Shimizu K, Goldfarb M, Perucho M, Wigler M. Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line. Proc Natl Acad Sci USA 1983;80(2): 383-7
143. Tanaka T. Ha-ras p21 in neuroblastoma: a new marker in prediction of patient outcome. Prog Clin Biol Res 1994;385: 275-80
144. Shimizu K, Goldfarb M, Suard Y, et al. Three human transforming genes are related to the viral ras oncogenes. Proc Natl Acad Sci USA 1983;80(8): 2112-16
145. Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2010;141(7): 1117-34 • This is an excellent review of RTKs, as well as their activation, signaling and inhibition.
146. Nikonova AS, Astsaturov I, Serebriiskii IG, et al. Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol Life Sci 2013;70(4): 661-87
147. Otto T, Horn S, Brockmann M, et al. Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell 2009;15(1): 67-78 • This paper describes a new function of AURKA in stablizing the MYCN protein, which makes it an attractive target, especially for high-risk NBs with MYCN amplification.
148. Carol H, Boehm I, Reynolds CP, et al. Efficacy and pharmacokinetic/ pharmacodynamic evaluation of the Aurora kinase A inhibitor MLN8237 against preclinical models of pediatric cancer. Cancer Chemother Pharmacol 2011;68(5): 1291-304
149. Maris JM, Morton CL, Gorlick R, et al. Initial testing of the aurora kinase A inhibitor MLN8237 by the Pediatric Preclinical Testing Program (PPTP). Pediatr Blood Cancer 2010;55(1): 26-34
150. Maugeri-Sacca M, Bartucci M, De Maria R. Checkpoint kinase 1 inhibitors for potentiating systemic anticancer therapy. Cancer Treat Rev 2013;39(5): 525-33
151. Cole KA, Huggins J, Laquaglia M, et al. RNAi screen of the protein kinome identifies checkpoint kinase 1 (CHK1) as a therapeutic target in neuroblastoma. Proc Natl Acad Sci USA 2011;108(8): 3336-41
152. Hoglund A, Nilsson LM, Muralidharan SV, et al. Therapeutic implications for the induced levels of Chk1 in Mycexpressing cancer cells. Clin Cancer Res 2011;17(22): 7067-79 • These reports by Cole et al., and Hoglund et al., suggest CHK1 is a therapeutic target for a subset of highrisk NBs.
153. Russell MR, Levin K, Rader J, et al. Combination therapy targeting the Chk1 and Wee1 kinases shows therapeutic efficacy in neuroblastoma. Cancer Res 2013;73(2): 776-84
154. Walton MI, Eve PD, Hayes A, et al. CCT244747 is a novel potent and selective CHK1 inhibitor with oral efficacy alone and in combination with genotoxic anticancer drugs. Clin Cancer Res 2012;18(20): 5650-61
155. Xu H, Cheung IY, Wei XX, et al. Checkpoint kinase inhibitor synergizes with DNA-damaging agents in G1 checkpoint-defective neuroblastoma. Int J Cancer 2011;129(8): 1953-62
156. Condorelli F, Gnemmi I, Vallario A, et al. Inhibitors of histone deacetylase (HDAC) restore the p53 pathway in neuroblastoma cells. Br J Pharmacol 2008;153(4): 657-68
157. Fouladi M, Park JR, Stewart CF, et al. Pediatric phase I trial and pharmacokinetic study of vorinostat: a Children's Oncology Group phase I consortium report. J Clin Oncol 2010;28(22): 3623-9
158. George RE, Lahti JM, Adamson PC, et al. Phase I study of decitabine with doxorubicin and cyclophosphamide in children with neuroblastoma and other solid tumors: a Children's Oncology Group study. Pediatr Blood Cancer 2010;55(4): 629-38
159. Mueller S, Yang X, Sottero TL, et al. Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma: efficacy and underlying mechanisms. Cancer Lett 2011;306(2): 223-9
160. Witt O, Milde T, Deubzer HE, et al. Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma or leukemia. Klin Padiatr 2012;224(6): 398-403
161. Chesler L, Schlieve C, Goldenberg DD, et al. Inhibition of phosphatidylinositol 3-kinase destabilizes Mycn protein and blocks malignant progression in neuroblastoma. Cancer Res 2006;66(16): 8139-46
162. Dam V, Morgan BT, Mazanek P, Hogarty MD. Mutations in PIK3CA are infrequent in neuroblastoma. BMC Cancer 2006;6: 177
163. Tivnan A, Orr WS, Gubala V, et al. Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a using antidisialoganglioside GD2 coated nanoparticles. PLoS One 2012;7(5):e38129