Preclinical drug development for childhood cancer

Expert Opinion on Drug Discovery

Volumn 6, Issue 1, 2011, Pages 49-64

  Moreno, Lucas ^a,b   Chesler, Louis ^a,b   Hargrave, Darren ^b   Eccles, Suzanne A ^c   Pearson, Andrew D J ^a,b  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^c IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

Author keywords

Animal models; Cancer; Cell lines; Children; Drug development; Targeted therapy

Indexed keywords

2 CHLORO N [4 CHLORO 3 (2 PYRIDINYL)PHENYL] 4 METHANESULFONYLBENZAMIDE; 3 [1 (2,6 DICHLORO 3 FLUOROPHENYL)ETHOXY] 5 [1 (4 PIPERIDINYL) 1H PYRAZOL 4 YL] 2 PYRIDINYLAMINE; 4 [2 (4 AMINO 1,2,5 OXADIAZOL 3 YL) 1 ETHYL 7 (3 PIPERIDINYLMETHOXY) 1H IMIDAZO[4,5 C]PYRIDIN 4 YL] 2 METHYL 3 BUTYN 2 OL; 4 [4 [2 (4 CHLOROPHENYL) 5,5 DIMETHYL 1 CYCLOHEXEN 1 YLMETHYL] 1 PIPERAZINYL] N [4 [3 MORPHOLINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 (TRIFLUOROMETHYLSULFONYL)BENZENESULFONYL]BENZAMIDE; ALVESPIMYCIN; ANTINEOPLASTIC AGENT; AZD 8055; BMS 754807; BORTEZOMIB; CIXUTUMUMAB; DASATINIB; DINACICLIB; ISPINESIB; LAPATINIB; MLN 8237; PG 11047; PR 104; RAPAMYCIN; SAR 3419; SELUMETINIB; SORAFENIB; SUNITINIB; SW 001; TOPOTECAN; UNCLASSIFIED DRUG; VORINOSTAT;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; ASTROCYTOMA; CANCER CELL CULTURE; CANCER INCIDENCE; CANCER SURVIVAL; CANCER THERAPY; CELL CYCLE REGULATION; CHILDHOOD CANCER; DRUG EFFICACY; DRUG MECHANISM; EPENDYMOMA; EWING SARCOMA; GERM CELL TUMOR; GLIOBLASTOMA; HODGKIN DISEASE; HUMAN; HUMAN CELL CULTURE; MEDULLOBLASTOMA; NEPHROBLASTOMA; NEUROBLASTOMA; NONHODGKIN LYMPHOMA; NONHUMAN; OSTEOSARCOMA; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REVIEW; RHABDOMYOSARCOMA; RNA INTERFERENCE; TUMOR XENOGRAFT;

EID: 78650673354     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441.2011.537652     Document Type: Review

References (91)

1. Boklan J. Little patients, losing patience: Pediatric cancer drug development. Mol Cancer Ther 2006;5(8):1905-8
2. Balis FM. The challenge of developing new therapies for childhood cancers. Oncologist 1997;2(1):I-II
3. Balis FM, Fox E, Widemann BC, et al. Clinical drug development for childhood cancers. Clin Pharmacol Ther 2009;85(2):127-9
4. Altekruse SF, Krapcho KCM, Neyman N, et al., editors, SEER Cancer Statistics Review, 1975-2007, National Cancer Institute. Bethesda, MD. Available from: Http://seer.cancer. gov/csr/1975-2007/, based on November 2009 SEER data submission, posted to the SEER web site 2010
5. Meshinchi S, Woods WG, Stirewalt DL, et al. Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia. Blood 2001;97(1):89-94
6. Arico M, Schrappe M, Hunger SP, et al. Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between 1995 and 2005. J Clin Oncol 2010;28(31):4755-61
7. Houghton PJ, Adamson PC, Blaney S, et al. Testing of new agents in childhood cancer preclinical models: Meeting summary. Clin Cancer Res 2002;8(12):3646-57 Summary of the cell lines and animal models for the Pediatric Preclinical Testing Program.
8. Houghton PJ, Morton CL, Tucker C, et al. The pediatric preclinical testing program: Description of models and early testing results. Pediatr Blood Cancer 2007;49(7):928-40
9. Houghton P. Pediatric Preclinical Testing Program (PPTP). Available from: Http://pptp.nchresearch.org/index.html [Last accessed 8 July 2010]
10. Neale G, Su X, Morton CL, et al. Molecular characterization of the pediatric preclinical testing panel. Clin Cancer Res 2008;14(14):4572-83
11. Zwaan CM, Kearns P, Caron H, et al. The role of the 'innovative therapies for children with cancer' (ITCC) European consortium. Cancer Treat Rev 2010;36(4):328-34
12. A review on the objectives and achievements of the ITCC consortium. 12. ITCC, Innovative Therapies for Children with Cancer (ITCC) European Consortium. Available from: Http://www.itcc-consortium.org/ [Last accessed 8 July 2010]
13. KCK, Kids Cancer Kinome. Available from: Http://www.kidscancerkinome.org/ [Last accessed 8 July 2010]
14. Holst MI, Westerhout EM, Kool M, et al. Targeting overexpressed Aurora kinases in childhood medulloblastoma: Anti-proliferative effects of small molecule inhibitors ZM44739, VX680 and shRNA. XVIIth International Congress of Neuropathology, Salzburg, Austria; 2010
15. OLPA, U.S.O.o.L.P.a.A., Best Pharmaceuticals for Children Act, Public Law 107-109. Available from: Http://olpa.od.nih.gov/legislation/107/ publiclaws/1best.asp [Last accessed 8 July 2010]
16. EMA, E.M.A., Medicines for children. Available from: Http://www.ema. europa.eu/htms/human/paediatrics/introduction. htm [Last accessed 8 July 2010]
17. EMA, E.M.A., REGULATION (EC) No 1901/2006 on medicinal products for paediatric use. Available from: Http:// ec.europa.eu/health/files/eudralex/vol- 1/reg-2006-1901/reg-2006-1901-en.pdf [Last accessed 8 July 2010]
18. EMA, E.M.A., Nonclinical Evaluation for Anticancer Pharmaceuticals, EMEA/CHMP/ICH/646107/2008. Available from: Http://www.ema.europa.eu/pdfs/ human/ich/64610708enfin.pdf [Last accessed 8 July 2010]
19. EMA, E.M.A., Guideline on the need for non-clinical testing in juvenile animals on human pharmaceuticals for pediatric indications. EMEA/CHMP/ SWP/169215/2005. Available from: Http://www.ema.europa.eu/pdfs/human/swp/ 16921505en.pdf [Last accessed 8 July 2010]
20. Smith M, Bernstein M, Bleyer WA, et al. Conduct of phase I trials in children with cancer. J Clin Oncol 1998;16(3):966-78 Consensus document that reviews the requirements for Phase I trials in children, emphasising the need for adequate preclinical research.
21. Estlin EJ, Ablett S, Newell DR, et al. Phase I trials in paediatric oncology-the European perspective. The New Agents Group of the United Kingdom Childrens Cancer Study Group. Invest New Drugs 1996;14(1):23-32
22. Houghton PJ, Cheshire PJ, Myers L, et al. Evaluation of 9-dimethylaminomethyl-10- hydroxycamptothecin against xenografts derived from adult and childhood solid tumors. Cancer Chemother Pharmacol 1992;31(3):229-39
23. Carol H, Houghton PJ, Morton CL, et al. Initial testing of topotecan by the pediatric preclinical testing program. Pediatr Blood Cancer 2010;54(5):707-15
24. Kelland LR. Of mice and men: Values and liabilities of the athymic nude mouse model in anticancer drug development. Eur J Cancer 2004;40(6):827-36
25. Huse JT, Holland EC. Genetically engineered mouse models of brain cancer and the promise of preclinical testing. Brain Pathol 2009;19(1):132-43
26. Sharpless NE, Depinho RA. The mighty mouse: Genetically engineered mouse models in cancer drug development. Nat Rev Drug Discov 2006;5(9):741-54
27. Mueller-Klieser W. Three-dimensional cell cultures: From molecular mechanisms to clinical applications. Am J Physiol 1997;273(4 Pt 1):C1109-23
28. Friedrich J, Ebner R, Kunz-Schughart LA. Experimental anti-tumor therapy in 3-D: Spheroids-old hat or new challenge? Int J Radiat Biol 2007;83(11-12):849-71
29. Voskoglou-Nomikos T, Pater JL, Seymour L. Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res 2003;9(11):4227-39
30. Kerbel RS. Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans: Better than commonly perceived-but they can be improved. Cancer Biol Ther 2003;2(4 Suppl 1):S134-9
31. Johnson JI, Decker S, Zaharevitz D, et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer 2001;84(10):1424-31
32. Bax DA, Little SE, Gaspar N, et al. Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development. PLoS One 2009;4(4):e5209
33. Yamada KM, Cukierman E. Modeling tissue morphogenesis and cancer in 3D. Cell 2007;130(4):601-10
34. De Witt Hamer PC, Van Tilborg AA, Eijk PP, et al. The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in spheroids. Oncogene 2008;27(14):2091-6
35. Ernst A, Hofmann S, Ahmadi R, et al. Genomic and expression profiling of glioblastoma stem cell-like spheroid cultures identifies novel tumor-relevant genes associated with survival. Clin Cancer Res 2009;15(21):6541-50
36. Friedrich J, Seidel C, Ebner R, et al. Spheroid-based drug screen: Considerations and practical approach. Nat Protocol 2009;4(3):309-24
37. Workman P, Aboagye EO, Balkwill F, et al. Guidelines for the welfare and use of animals in cancer research. Br J Cancer 2010;102(11):1555-77
38. Heyer J, Kwong LN, Lowe SW, et al. Non-germline genetically engineered mouse models for translational cancer research. Nat Rev Cancer 2010;10(7):470-80
39. Olive KP, Jacobetz MA, Davidson CJ, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009;324(5933):1457-61
40. Weiss WA, Aldape K, Mohapatra G, et al. Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J 1997;16(11):2985-95 Describes the establishment of a transgenic mouse model for MYCN.
41. Chesler L, Goldenberg DD, Seales IT, et al. Malignant progression and blockade of angiogenesis in a murine transgenic model of neuroblastoma. Cancer Res 2007;67(19):9435-42
42. Sarker D, Workman P. Pharmacodynamic biomarkers for molecular cancer therapeutics. Adv Cancer Res 2007;96:213-68
43. Weissleder R, Pittet MJ. Imaging in the era of molecular oncology. Nature 2008;452(7187):580-9
44. Kimura H, Ng JM, Curran T. Transient inhibition of the Hedgehog pathway in young mice causes permanent defects in bone structure. Cancer Cell 2008;13(3):249-60
45. Broniscer A, Gajjar A. Supratentorial high-grade astrocytoma and diffuse brainstem glioma: Two challenges for the pediatric oncologist. Oncologist 2004;9(2):197-206
46. Paugh BS, Qu C, Jones C, et al. Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol 2010;28(18):3061-8 Highlights the differences between adult and paediatric high grade gliomas with gene-expression signatures.
47. Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17(1):98-110
48. Van Meir EG, Hadjipanayis CG, Norden AD, et al. Exciting new advances in neuro-oncology: The avenue to a cure for malignant glioma. CA Cancer J Clin 2010;60(3):166-93
49. Servidei T, Riccardi A, Sanguinetti M, et al. Increased sensitivity to the platelet-derived growth factor (PDGF) receptor inhibitor STI571 in chemoresistant glioma cells is associated with enhanced PDGF-BB-mediated signaling and STI571-induced Akt inactivation. J Cell Physiol 2006;208(1):220-8
50. Oertel S, Krempien R, Lindel K, et al. Human glioblastoma and carcinoma xenograft tumors treated by combined radiation and imatinib (Gleevec). Strahlenther Onkol 2006;182(7):400-7
51. Pollack IF, Jakacki RI, Blaney SM, et al. Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: A Pediatric Brain Tumor Consortium report. Neuro Oncol 2007;9(2):145-60
52. Porkka K, Koskenvesa P, Lundan T, et al. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Blood 2008;112(4):1005-12
53. Kolb EA, Gorlick R, Houghton PJ, et al. Initial testing of dasatinib by the pediatric preclinical testing program. Pediatr Blood Cancer 2008;50(6):1198-206
54. Hargrave D, Bartels U, Bouffet E. Diffuse brainstem glioma in children: Critical review of clinical trials. Lancet Oncol 2006;7(3):241-8
55. Zarghooni M, Bartels U, Lee E, et al. Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol 2010;28(8):1337-44
56. Hashizume R, Ozawa T, Dinca EB, et al. A human brainstem glioma xenograft model enabled for bioluminescence imaging. J Neurooncol 2010;96(2):151-9
57. Jallo GI, Volkov A, Wong C, et al. A novel brainstem tumor model: Functional and histopathological characterization. Childs Nerv Syst 2006;22(12):1519-25
58. Becher OJ, Hambardzumyan D, Walker TR, et al. Preclinical evaluation of radiation and perifosine in a genetically and histologically accurate model of brainstem glioma. Cancer Res 2010;70(6):2548-57
59. Geoerger B, Hargrave D, Thomas F, et al. Pharmacokinetic and biological study of erlotinib in children as monotherapy for refractory brain tumors or with radiation for newly diagnosed brain stem gliomas. J Clin Oncol 2009;27(15S):abstract 10019
60. Maris JM, Hogarty MD, Bagatell R, et al. Neuroblastoma. Lancet 2007;369(9579):2106-20
61. Matthay KK, Reynolds CP, Seeger RC, et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: A children's oncology group study. J Clin Oncol 2009;27(7):1007-13
62. Maris JM. Recent advances in neuroblastoma. N Engl J Med 2010;362(23):2202-11
63. Mosse YP, Wood A, Maris JM. Inhibition of ALK signaling for cancer therapy. Clin Cancer Res 2009;15(18):5609-14 . A review of the role of ALK in human cancer, with updated information on preclinical studies with ALK inhibitors.
64. 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
65. COG-ADVL0912, N., U.S. National Cancer Institute, Phase I/II Study of MET Tyrosine Kinase Inhibitor PF-02341066 in Children With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma. Available from: Http://www.cancer.gov/ clinicaltrials/COG-ADVL0912 [Last accessed 8 July 2010]
66. Gazdar AF. Personalized medicine and inhibition of EGFR signaling in lung cancer. N Engl J Med 2009;361(10):1018-20
67. Passoni L, Longo L, Collini P, et al. Mutation-independent anaplastic lymphoma kinase overexpression in poor prognosis neuroblastoma patients. Cancer Res 2009;69(18):7338-46
68. Crawford JR, MacDonald TJ, Packer RJ. Medulloblastoma in childhood: New biological advances. Lancet Neurol 2007;6(12):1073-85
69. Romer J, Curran T. Targeting medulloblastoma: Small-molecule inhibitors of the Sonic Hedgehog pathway as potential cancer therapeutics. Cancer Res 2005;65(12):4975-8
70. Hidalgo M, Maitra A. The hedgehog pathway and pancreatic cancer. N Engl J Med 2009;361(21):2094-6
71. Thompson MC, Fuller C, Hogg TL, et al. Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 2006;24(12):1924-31
72. Kool M, Koster J, Bunt J, et al. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 2008;3(8):e3088
73. Berman DM, Karhadkar SS, Hallahan AR, et al. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science 2002;297(5586):1559-61
74. Rudin CM, Hann CL, Laterra J, et al. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 2009;361(12):1173-8
75. St-Jacques B, Hammerschmidt M, McMahon AP. Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev 1999;13(16):2072-86
76. Yauch RL, Dijkgraaf GJ, Alicke B, et al. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science 2009;326(5952):572-4
77. Hughes DP. Novel agents in development for pediatric sarcomas. Curr Opin Oncol 2009;21(4):332-7
78. Prieur A, Tirode F, Cohen P, et al. EWS/FLI-1 silencing and gene profiling of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3. Mol Cell Biol 2004;24(16):7275-83
79. Kim SY, Toretsky JA, Scher D, et al. The role of IGF-1R in pediatric malignancies. Oncologist 2009;14(1):83-91 . A comprehensive review of the role of the IGF-1R pathway in childhood cancers including biological, preclinical and clinical studies.
80. Baserga R, Peruzzi F, Reiss K. The IGF-1 receptor in cancer biology. Int J Cancer 2003;107(6):873-7
81. Olmos D, Postel-Vinay S, Molife LR, et al. Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: A phase 1 expansion cohort study. Lancet Oncol 2010;11(2):129-35
82. Kolb EA, Gorlick R, Houghton PJ, et al. Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program. Pediatr Blood Cancer 2008;50(6):1190-7
83. 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
84. Negroni A, Scarpa S, Romeo A, et al. Decrease of proliferation rate and induction of differentiation by a MYCN antisense DNA oligomer in a human neuroblastoma cell line. Cell Growth Differ 1991;2(10):511-18
85. Schmidt ML, Salwen HR, Manohar CF, et al. The biological effects of antisense N-myc expression in human neuroblastoma. Cell Growth Differ 1994;5(2):171-8
86. 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
87. 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 This study proved that inhibition of PI3K pathway can destabilise MYCN and obtain tumour responses in transgenic mouse models with MYCN amplified neuroblastoma.
88. Molenaar JJ, Ebus ME, Geerts D, et al. Inactivation of CDK2 is synthetically lethal to MYCN over-expressing cancer cells. Proc Natl Acad Sci USA 2009;106(31):12968-73
89. 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
90. COG-ADVL0921, N., U.S. National Cancer Institute, Phase II Study of Aurora A Kinase Inhibitor MLN8237 in Pediatric Patients With Recurrent or Refractory Solid Tumors or Leukemia. Available from: Http://www.cancer.gov/ clinicaltrials/COG-ADVL0921 [Last accessed 8 July 2010]
91. Mosse YP, Lipsitz EG, Maris JM, et al. A pediatric phase I trial and pharmacokinetic study of MLN8237, an oral selective small molecule inhibitor of aurora a kinase: A Children's Oncology Group Phase I Consortium study. J Clin Oncol 2010;28(15S):abstract 95293