Recent therapeutic advances for treating medulloblastoma: Focus on new molecular targets

CNS and Neurological Disorders - Drug Targets

Volumn 9, Issue 3, 2010, Pages 335-348

  Schmidt, A L ^a,b   Brunetto, A L ^a,b   Schwartsmann, G ^a,b   Roesler, R ^a,b   Abujamra, A L ^a,b  

^a FEDERAL UNIVERSITY OF RIO GRANDE DO SUL   (Brazil)

^b National Institute for Translational Medicine INCT TM   (Brazil)

Author keywords

Cancer therapies; CNS tumor; Medulloblastoma; Molecular targets; Translational studies

Indexed keywords

BETA CATENIN; CISPLATIN; CYCLIN D1; CYCLOPAMINE; CYCLOPHOSPHAMIDE; DELTA LIGAND; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; FRIZZLED PROTEIN; GAMMA SECRETASE INHIBITOR; GDC 0449; HHANTAG 691; LAPATINIB; LIGAND; LOMUSTINE; MYC PROTEIN; NOTCH RECEPTOR; PROTEIN KINASE B; PROTEIN P53; PROTEIN PATCHED 1; SOMATOMEDIN C RECEPTOR; SONIC HEDGEHOG PROTEIN; SORAFENIB; SURVIVIN; TIPIFARNIB; TRANSCRIPTION FACTOR GLI1; TRANSCRIPTION FACTOR HES 1; TRANSCRIPTION FACTOR SOX; TRANSCRIPTION FACTOR SOX4; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINCRISTINE; WNT PROTEIN;

APOPTOSIS; ARTICLE; BRAIN INJURY; BRAIN TUMOR; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; CARDIOTOXICITY; CELL DEATH; CELL PROLIFERATION; DISEASE COURSE; DISEASE EXACERBATION; DISEASE FREE SURVIVAL; GENE EXPRESSION; GROWTH HORMONE DEFICIENCY; GROWTH RETARDATION; HEARING LOSS; HORMONE SUBSTITUTION; HUMAN; LUNG TOXICITY; MEDULLOBLASTOMA; MOLECULARLY TARGETED THERAPY; NEOPLASM; NONHUMAN; OTOTOXICITY; PROGNOSIS; PROGRESSION FREE SURVIVAL; QUALITY OF LIFE; RADIATION DOSE; RELAPSE; STEM CELL; TURCOT SYNDROME; UPREGULATION;

EID: 77954341523     PISSN: 18715273     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152710791292602     Document Type: Article

References (183)

1. CBTRUS (2007-2008). Statistical Report: Primary Brain Tumors in the United States, 2000-2004. Published by the Central Brain Tumor Registry of the United States, 2008.
2. Crawford, J.R.; MacDonald, T.J.; Packer, R.J. Medulloblastoma in childhood: new biological advances. Lancet Neurol., 2007, 6, 1073-1085.
3. Katsetos, C.D.; Del Valle, L.; Legido, A.; de Chadarevian, J.P.; Perentes, E.; Mork, S.J. On the neuronal/neuroblastic nature of medulloblastomas: a tribute to Pio del Rio Hortega and Moises Polak. Acta Neuropathol. (Berl.), 2003, 105, 1-13.
4. Schüller, U.; Heine, V.M.; Mao, J.; Kho, A.T.; Dillon, A.K.; Han, Y.G.; Huillard, E.; Sun, T.; Ligon, A.H.; Qian, Y.; Ma, Q.; Alvarez-Buylla, A.; McMahon, A.P.; Rowitch, D.H.; Ligon, K.L. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Hedgehog-induced medulloblastoma. Cancer Cell, 2008, 12, 123-134.
5. Eberhart, C.G. In search of the medulloblast: neural stem cells and embryonal brain tumors. Neurosurg. Clin. N. Am., 2007, 18(1), 59-69.
6. Yang, Z.J.; Ellis, T.; Markant, S.L.; Read, T.A.; Kessler, J.D.; Bourboulas, M.; Schüller, U.; Machold, R.; Fishell, G.; Rowitch, D.H.; Wainwright, B.J.; Wechsler-Reya, R.J. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell, 2008, 14, 135-145.
7. Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.; Burger, P.C.; Jouvet, A.; Scheithauer, B.W.; Kleihues, P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol., 2007, 114, 97-109.
8. de Bont, J.M.; Packer, R.J.; Michiels, E.M.; den Boer, M.L.; Pieters, R. Biological background of pediatric medulloblastoma and ependymoma: a review from a translational research perspective. Neurol. Oncol., 2008, 10(6), 1040-1060.
9. Packer, R.J.; Vezina, G. Management of and prognosis with medulloblastoma:therapy at a crossroads. Arch Neurol., 2008, 65(11), 1419-1424.
10. Carlotti, C.G. Jr.; Smith, C.; Rutka, J.T. The molecular genetics of medulloblastoma: an assessment of new therapeutic targets. Neurosurg. Rev., 2008, 31(4), 359-369.
11. Wrensch, M.; Minn, Y.; Chew, T.; Bondy, M.; Berger, M.S. Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol., 2002, 4, 278-299.
12. Fouladi, M.; Chintagumpala, M.; Ashley, D.; Kellie, S.; Gururangan, S.; Hassall, T.; Gronewold, L.; Stewart, C.F.; Wallace, D.; Broniscer, A.; Hale, G.A.; Kasow, K.A.; Merchant, T.E.; Morris, B.; Krasin, M.; Kun, L.E.; Boyett, J.M.; Gajjar, A. Amifostine protects against cisplatin-induced ototoxicity in children with average-risk medulloblastoma. J. Clin. Oncol., 2008, 26(22), 3749-3755.
13. Merchant, T.E.; Kun, L.E.; Krasin, M.J.; Wallace, D.; Chintagumpala, M.M.; Woo, S.Y.; Ashley, D.M.; Sexton, M.; Kellie, S.J.; Ahern, V.; Gajjar, A. Multi-institution prospective trial of reduced-dose craniospinal irradiation (23.4 Gy) followed by conformal posterior fossa (36 Gy) and primary site irradiation (55.8 Gy) and dose-intensive chemotherapy for average-risk medulloblastoma. Int. J. Radiat. Oncol. Biol. Phys., 2008, 70(3), 782-787.
14. Taylor, R.E.; Bailey, C.C.; Robinson, K.; Weston, C.L.; Ellison, D.; Ironside, J.; Lucraft, H.; Gilbertson, R.; Tait, D.M.; Walker, D.A.; Pizer, B.L.; Imeson, J.; Lashford, L.S.; International Society of Paediatric Oncology; United Kingdom Children's Cancer Study Group. Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children's Cancer Study Group PNET-3 Study. J. Clin. Oncol., 2003, 21(8), 1582-1591.
15. Packer, R.J.; Gajjar, A.; Vezina, G.; Rorke-Adams, L.; Burger, P.C.; Robertson, P.L.; Bayer, L.; LaFond, D.; Donahue, B.R.; Marymont, M.H.; Muraszko, K.; Langston, J.; Sposto, R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J. Clin. Oncol., 2006, 24, 4202-4208.
16. Bouffet, E.; Doz, F.; Demaille, M.C.; Tron, P.; Roche, H.; Plantaz, D.; Thyss, A.; Stephan, J.L.; Lejars, O.; Sariban, E.; Buclon, M.; Zücker, J.M.; Brunat-Mentigny, M.; Bernard, J.L.; Gentet, J.C. Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse? Br. J. Cancer, 1998, 77(8), 1321-1326.
17. Palmer, S.L.; Reddick, W.E.; Gajjar, A. Understanding the cognitive impact on children who are treated for medulloblastoma. J. Pediatr. Psychol., 2007, 32, 1040-1049.
18. Ris, M.D.; Packer, R.; Goldwein, J.; Jones-Wallace, D.; Boyett, J.M. Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children's Cancer Group study. J. Clin. Oncol., 2001, 19, 3470-3476.
19. Radcliffe, J.; Packer, R.J.; Atkins, T.E.; Bunin, G.R.; Schut, L.; Goldwein, J.W.; Sutton, L.N. Three-and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain radiotherapy. Ann. Neurol., 1992, 32, 551-554.
20. Packer, R.J.; Boyett, J.M.; Janss, A.J.; Stavrou, T.; Kun, L.; Wisoff, J.; Russo, C.; Geyer, R.; Phillips, P.; Kieran, M.; Greenberg, M.; Goldman, S.; Hyder, D.; Heideman, R.; Jones-Wallace, D.; August, G.P.; Smith, S.H.; Moshang, T. Jr. Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. J. Clin. Oncol., 2001, 19, 480-487.
21. Gessi, M.; Maderna, E.; Guzzetti, S.; Cefalo, G.; Massimino, M.; Solero, C.L.; Finocchiaro, G.; Pollo, B. Radiation-induced glioblastoma in a medulloblastoma patient: a case report with molecular features. Neuropathology, 2008, 28, 633-639.
22. Perez-Martinez, A.; Lassaletta, A.; Gonzalez-Vicent, M.; Sevilla, J.; Diaz, M.A.; Madero, L. High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors. J. Neurooncol., 2005, 71, 33-38.
23. MacDonald, T.J.; Rood, B.R.; Santi, M.R.; Vezina, G.; Bingaman K.; Cogen, P.H.; Packer, R.J. Advances in the diagnosis, molecular genetics, and treatment of pediatric embryonal CNS tumors. Oncologist, 2003, 8,174-186.
24. Taylor, R.E.; Bailey, C.C.; Robinson, K.J.; Weston, C.L.; Walker, D.A.; Ellison, D.; Ironside, J.; Pizer, B.L.; Lashford, L.S. Outcome for patients with metastatic (M2-3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy. Eur. J. Cancer, 2005, 41(5), 727-734.
25. von Hoff, K.; Hinkes, B.; Gerber, N.U.; Deinlein, F.; Mittler, U.; Urban, C.; Benesch, M.; Warmuth-Metz, M.; Soerensen, N.; Zwiener, I.; Goette, H.; Schlegel, P.G.; Pietsch, T.; Kortmann, R.D.; Kuehl, J.; Rutkowski, S. Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT'91. Eur. J. Cancer, 2009, 45(7), 1209-1217.
26. Grodman, H.; Wolfe, L.; Kretschmar, C. Outcome of patients with recurrent medulloblastoma or central nervous system germinoma treated with low dose continuous intravenous etoposide along with dose-intensive chemotherapy followed by autologous hematopoietic stem cell rescue. Pediatr. Blood Cancer, 2009, 53(1), 33-36.
27. Skowrońska-Gardas, A. A literature review of the recent radiotherapy clinical trials in pediatric brain tumors. Rev. Recent Clin. Trials, 2009, 4(1), 42-55.
28. Garrè, M.L.; Cama, A.; Bagnasco, F.; Morana, G.; Giangaspero, F.; Brisigotti, M.; Gambini, C.; Forni, M.; Rossi, A.; Haupt, R.; Nozza, P.; Barra, S.; Piatelli, G.; Viglizzo, G.; Capra, V.; Bruno, W.; Pastorino, L.; Massimino, M.; Tumolo, M.; Fidani, P.; Dallorso, S.; Schumacher, R.F.; Milanaccio, C.; Pietsch, T. Medulloblastoma variants: age-dependent occurrence and relation to Gorlin syndrome-a new clinical perspective. Clin. Cancer Res., 2009, 15(7), 2463-2471.
29. Gilbertson, R.J.; Gajjar, A. Molecular biology of medulloblastoma: will it ever make a difference to clinical management? J. Neurooncol., 2005, 75(3), 273-278.
30. Zurawel, R.H.; Allen, C.; Wechsler-Reya, R.; Scott, M.P.; Raffel, C. Evidence that haploinsufficiency of Ptch leads to medulloblastoma in mice. Genes Chromosomes Cancer, 2000, 28, 77-81.
31. Dong, J.; Gailani, M.R.; Pomeroy, SL.; Reardon, D.; Bale, A.E. Identification of PATCHED mutations in medulloblastomas by direct sequencing. Hum. Mutat., 2000, 16, 89-90.
32. Pomeroy, S.L.; Tamayo, P.; Gaasenbeek, M.; Sturla, L.M.; Angelo, M.; McLaughlin, M.E.; Kim, J.Y.; Goumnerova L.C.; Black, P.M.; Lau, C.; Allen, J.C.; Zagzag, D.; Olson, J.M.; Curran, T.; Wetmore, C.; Biegel, J.A.; Poggio, T.; Mukherjee, S.; Rifkin, R.; Califano, A.; Stolovitzky, G.; Louis, D.N.; Mesirov, J.P.; Lander, E.S.; Golub, T.R. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature, 2002, 415, 436-442.
33. Raffel, C.; Jenkins, R.B.; Frederick, L.; Hebrink, D.; Alderete, B.; Fults, D.W.; James, C.D. Sporadic medulloblastomas contain PTCH mutation. Cancer Res., 1997, 57, 842-845.
34. Taylor, M.D.; Liu, L.; Raffel, C.; Hui, C.C.; Mainprize, T.G.; Zhang, X.; Agatep, R.; Chiappa, S.; Gao, L.; Lowrance, A.; Hao, A.; Goldstein, A.M.; Stavrou, T.; Scherer, S.W.; Dura, W.T.; Wainwright, B.; Squire, J.A.; Rutka, J.T.; Hogg, D. Mutations in SUFU predispose to medulloblastoma. Nat. Genet., 2002, 31, 306-310.
35. Dakubo, G.D.; Mazerolle, C.J.; Wallace, V.A. Expression of Notch and Wnt pathway components and activation of Notch signaling in medulloblastomas from heterozygous patched mice. J. Neurooncol., 2006, 79(3), 221-227.
36. Romer, J.T.; Kimura, H.; Magdaleno, S.; Sasai, K.; Fuller, C.; Baines, H.; Connelly, M.; Stewart, C.F.; Gould, S.; Rubin, L.L.; Curran, T. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/-)p53(-/-) mice. Cancer Cell, 2004, 6(3), 229-240.
37. Yauch, R.L.; Dijkgraaf G.J.; Alicke, B.; Januario, T.; Ahn, C.P.; Holcomb, T.; Pujara, K.; Stinson, J.; Callahan, C.A.; Tang, T.; Bazan, J.F.; Kan, Z.; Seshagiri, S.; Hann, C.L.; Gould, S.E.; Low, J.A.; Rudin, C.M.; de Sauvage, F.J. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science, 2009, 326(5952), 572-574.
38. Rudin, C.M.; Hann, C.L.; Laterra, J.; Yauch, R.L.; Callahan, C.A.; Fu, L.; Holcomb, T.; Stinson, J.; Gould, S.E.; Coleman, B.; LoRusso, P.M.; Von Hoff, D.D.; de Sauvage, F.J.; Low, J.A. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N. Engl. J. Med., 2009, 361(12), 1173-1178.
39. Sasai, K.; Romer, J.T.; Kimura, H.; Eberhart, D.E.; Rice, D.S.; Curran, T. Medulloblastomas derived from Cxcr6 mutant mice respond to treatment with a smoothened inhibitor. Cancer Res., 2007, 67, 3871-3877.
40. Berman, D.M.; Karhadkar, S.S.; Hallahan, A.R.; Pritchard, J.I.; Eberhart, C.G.; Watkins, D.N.; Chen, J.K.; Cooper, M.K.; Taipale, J.; Olson, J.M.; Beachy, P.A. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science, 2002, 297, 1559-1561.
41. Kimura, H.; Stephen, D.; Joyner, A.; Curran, T. Gli1 is important for medulloblastoma formation in Ptc1p/-mice. Oncogene, 2005, 24, 4026-4036.
42. Chen, J.K.; Taipale, J.; Young, K.E.; Maiti, T.; Beachy, P.A. Small molecule modulation of smoothened activity. Proc. Natl. Acad. Sci. USA, 2002, 99, 14071-14076.
43. Bradbury, J. Hitting the target in medulloblastoma therapy. Drug Discov. Today, 2004, 9(23), 994-995.
44. Polakis, P. Wnt signaling and cancer. Genes Dev., 2000, 14(15), 1837-1851.
45. Novak, A.; Dedhar, S. Signaling through beta-catenin and Lef/Tcf. Cell Mol. Life Sci., 1999, 56(5-6), 523-537.
46. Clifford, S.C.; Lusher, M.E.; Lindsey, J.C.; Langdon, J.A.; Gilbertson, R.J.; Straughton, D.; Ellison, D.W. Wnt/Wingless pathway activation and chromosome 6 loss characterize a distinct molecular subgroup of medulloblastomas associated with a favorable prognosis. Cell Cycle, 2006, 5(22), 2666-2670.
47. Thompson, M.C.; Fuller, C.; Hogg, T.L.; Dalton, J.; Finkelstein, D.; Lau, C.C.; Chintagumpala, M.; Adesina, A.; Ashley, D.M.; Kellie, S.J.; Taylor, M.D.; Curran, T.; Gajjar, A.; Gilbertson, R.J. Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J. Clin. Oncol., 2006, 24, 1924-1931.
48. Ellison, D.W.; Onilude, O.E.; Lindsey, J.C.; Lusher, M.E.; Weston, C.L.; Taylor, R.E.; Pearson, A.D.; Clifford, S.C. Beta-Catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children's Cancer Study Group Brain Tumour Committee. J. Clin Oncol., 2005, 23(31), 7951-7957.
49. Haberler, C.; Slavc, I.; Czech, T.; Gelpi, E.; Heinzl, H.; Budka, H.; Urban, C.; Scarpatetti, M.; Ebetsberger-Dachs, G.; Schindler, C.; Jones, N.; Klein-Franke, A.; Maier, H.; Jauk, B.; Kiefer, A.; Hainfellner, J.A. Histopathological prognostic factors in medulloblastoma: high expression of survivin is related to unfavourable outcome. Eur. J. Cancer, 2006, 42(17), 2996-3003.
50. Bodey, B.; Bodey, V.; Siegel, S.E.; Kaiser, H.E. Survivin expression in childhood medulloblastomas: a possible diagnostic and prognostic marker. In Vivo, 2004, 18(6), 713-718.
51. Pizem, J.; Cört, A.; Zadravec-Zaletel, L.; Popovic, M. Survivin is a negative prognostic marker in medulloblastoma. Neuropathol. Appl. Neurobiol., 2005, 31(4), 422-428.
52. Fangusaro, J.R.; Jiang, Y.; Holloway, M.P.; Caldas, H.; Singh, V.; Boué, D.R.; Hayes, J.; Altura, R.A. Survivin, Survivin-2B, and Survivin-deltaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcome. Br. J. Cancer, 2005, 92(2), 359-365.
53. Zorn, A.M.; Barish, G.D.; Williams, B.O.; Lavender, P.; Klymkowsky, M.W.; Varmus, H.E. Regulation of Wnt signaling by Sox proteins: XSox17 alpha/beta and XSox3 physically interact with beta-catenin. Mol. Cell, 1999, 4(4), 487-498.
54. de Bont, J.M.; Kros, J.M.; Passier, M.M.; Reddingius, R.E.; Sillevis Smitt, P.A.; Luider, T.M.; den Boer, M.L.; Pieters, R. Differential expression and prognostic significance of SOX genes in pediatric medulloblastoma and ependymoma identified by microarray analysis. Neurooncology, 2008, 10(5), 648-660.
55. Lee, C.J.; Appleby, V.J.; Orme, A.T.; Chan, W.I.; Scotting, P.J. Differential expression of SOX4 and SOX11 in medulloblastoma. J. Neurooncol., 2002, 57(3), 201-214.
56. Neben, K.; Korshunov, A. Benner, A.; Wrobel, G.; Hahn, M.; Kokocinski, F.; Golanov, A.; Joos, S.; Lichter, P. Microarray-based screening for molecular markers in medulloblastoma revealed STK15 as independent predictor for survival. Cancer Res., 2004, 64(9), 3103-3111.
57. Baron, M. An overview of the Notch signalling pathway. Semin. Cell Dev. Biol., 2003, 14(2), 113-119.
58. Adesina, A.M.; Nguyen, Y.; Mehta, V.; Takey, H.; Stangeby, P.; Crabtree, S.; Chintagumpala, M.; Gumerlock, M.K. FOXG1 dysregulation is a frequent event in medulloblastoma. J. Neurooncol., 2007, 85(2), 111-122.
59. Hallahan, A.R.; Pritchard, J.I.; Hansen, S.; Benson, M.; Stoeck, J.; Hatton, B.A.; Russell, T.L.; Ellenbogen, R.G.; Bernstein, I.D.; Beachy, P.A.; Olson, J.M. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res., 2004, 64(21), 7794-7800.
60. Marino, S. Medulloblastoma: developmental mechanisms out of control. Trends Mol. Med., 2005, 11(1), 17-22.
61. MacDonald, T.J.; Rood, B.R.; Santi, M.R.; Vezina, G.; Bingaman, K.; Cogen, P.H.; Packer, R.J. Advances in the diagnosis, molecular genetics, and treatment of pediatric embryonal CNS tumors. Oncologist, 2003, 8(2), 174-186.
62. Gilbertson, R.; Wickramasinghe, C.; Hernan, R.; Balaji, V.; Hunt, D.; Jones-Wallace, D.; Crolla, J.; Perry, R.; Lunec, J.; Pearson, A.; Ellison, D. Clinical and molecular stratification of disease risk in medulloblastoma. Br. J. Cancer, 2001, 85(5), 705-712.
63. Segal, R.A.; Goumnerova, L.C.; Kwon, Y.K.; Stiles, C.D.; Pomeroy, S.L. Expression of the neurotrophin receptor TrkC is linked to a favorable outcome in medulloblastoma. Proc. Natl. Acad. Sci. USA, 1994, 91, 12867-12871.
64. Grotzer, M.A.; Janss, A.J.; Fung, K.; Biegel, J.A.; Sutton, L.N.; Rorke, L.B.; Zhao, H.; Cnaan, A.; Phillips, P.C.; Lee, V.M.; Trojanowski, J.Q. TrkC expression predicts good clinical outcome in primitive neuroectodermal brain tumors. J. Clin. Oncol., 2000, 18, 1027-1035.
65. Kim, J.Y.; Sutton, M.E.; Lu, D.J.; Cho, T.A.; Goumnerova, L.C.; Goritchenko, L.; Kaufman, J.R.; Lam, K.K.; Billet, A.L.; Tarbell, N.J.; Wu, J.; Allen, J.C.; Stiles, C.D.; Segal, R.A.; Pomeroy, S.L. Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas. Cancer Res., 1999, 59, 711-719.
66. Marchetti, D.; Mrak, R.E.; Paulsen, D.D.; Sinnappah-Kang, N.D. Neurotrophin receptors and heparanase: a functional axis in human medulloblastoma invasion. J. Exp. Clin. Cancer Res., 2007, 26(1), 5-23.
67. Ohta, T.; Watanabe, T.; Katayama, Y.; Kurihara, J.; Yoshino, A.; Nishimoto, H.; Kishimoto, H. TrkA expression is associated with an elevated level of apoptosis in classic medulloblastomas. Neuropathology, 2006, 26(3), 170-177.
68. Antonelli, A.; Lenzi, L.; Nakagawara, A.; Osaki, T.; Chiaretti, A.; Aloe, L. Tumor suppressor proteins are differentially affected in human ependymoblastoma and medulloblastoma cells exposed to nerve growth factor. Cancer Invest., 2007, 25(2), 94-101.
69. Muragaki, Y.; Chou, T.T.; Kaplan, D.R.; Trojanowski, J.Q.; Lee, V.M. Nerve growth factor induces apoptosis in human medulloblastoma cell lines that express TrkA receptors. J. Neurosci., 1997, 17(2), 530-542.
70. Valderrama, X.; Rapin, N.; Verge, V.M.; Misra, V. Zhangfei induces the expression of the nerve growth factor receptor, trkA, in medulloblastoma cells and causes their differentiation or apoptosis. J. Neurooncol., 2009, 91(1), 7-17.
71. Antonelli, A.; Lenzi, L.; Nakagawara, A.; Osaki, T.; Chiaretti, A.; Aloe, L. Tumor suppressor proteins are differentially affected in human ependymoblastoma and medulloblastoma cells exposed to nerve growth factor. Cancer Invest., 2007, 25(2), 94-101.
72. Li, Y.; Lal, B.; Kwon, S.; Fan, X.; Saldanha, U.; Reznik, T.E.; Kuchner, E.B.; Eberhart, C.; Laterra, J.; Abounader, R. The scatter factor/hepatocyte growth factor: c-met pathway in human embryonal central nervous system tumor malignancy. Cancer Res., 2005, 65(20), 9355-9362.
73. Kongkham, P.N.; Northcott, P.A.; Ra, Y.S.; Nakahara, Y.; Mainprize, T.G.; Croul, S.E.; Smith, C.A.; Taylor, M.D.; Rutka, J.T. An epigenetic genome-wide screen identifies SPINT2 as a novel tumor suppressor gene in pediatric medulloblastoma. Cancer Res., 2008, 68(23), 9945-9953.
74. Li, Y.; Guessous, F.; Johnson, E.B.; Eberhart, C.G.; Li, X.N.; Shu, Q.; Fan, S.; Lal, B.; Laterra, J.; Schiff, D.; Abounader, R. Functional and molecular interactions between the HGF/c-Met pathway and cmyc in large-cell medulloblastoma. Lab. Invest., 2008, 88(2), 98-111.
75. Stearns, D.; Chaudhry, A.; Abel, T.W.; Burger, P.C.; Dang, C.V.; Eberhart, C.G. c-myc overexpression causes anaplasia in medulloblastoma. Cancer Res., 2006, 66(2), 673-681.
76. Provençal, M.; Labbé, D.; Veitch, R.; Boivin, D.; Rivard, G.E.; Sartelet, H.; Robitaille, Y.; Gingras, D.; Béliveau, R. C-met activation in medulloblastoma induces tissue factor expression and activity: effects on cell migration. Carcinogenesis, 2009, 30(7), 1089-1096.
77. Li, Y.; Fan, X.; Goodwin, C.R.; Laterra, J.; Xia, S. Hepatocyte growth factor enhances death receptor-induced apoptosis by upregulating DR5. BMC Cancer, 2008, 8, 325.
78. Binning, M.J.; Niazi, T.; Pedone, C.A.; Lal, B.; Eberhart, C.G.; Kim, K.J.; Laterra, J.; Fults, D.W. Hepatocyte growth factor and sonic Hedgehog expression in cerebellar neural progenitor cells costimulate medulloblastoma initiation and growth. Cancer Res., 2008, 68(19), 7838-7845.
79. Miettinen, P.J.; Berger, J.E.; Meneses, J.; Phung, Y.; Pedersen, R.A.; Werb, Z.; Derynck, R. Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature, 1995, 376(6538), 337-341.
80. Sibilia, M.; Wagner, E.F. Strain-dependent epithelial defects in mice lacking the EGF receptor. Science, 1995, 269(5221), 234-238.
81. Threadgill, D.W.; Dlugosz, A.A.; Hansen, L.A.; Tennenbaum, T.; Lichti, U.; Yee, D.; LaMantia, C.; Mourton, T.; Herrup, K.; Harris, R.C.; Barnard, J.A.; Yuspa, S.H.; Coffey, R.J.; Magnuson, T. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science, 1995, 269(5221), 230-234.
82. Gilbertson, R.J.; Pearson, A.D.; Perry, R.H.; Jaros, E.; Kelly, P.J. Prognostic significance of the c-erbB-2 oncogene product in childhood medulloblastoma. Br. J. Cancer, 1995, 71, 473-477.
83. Bal, M.M.; Das Rodotra, B.; Srinivasan, R.; Sharma, S.C. Expression of c-erbB-4 in medulloblastoma and its correlation with prognosis. Histopathology, 2006, 49(1), 92-93.
84. Hernan, R.; Fasheh, R.; Calabrese, C.; Frank, A.J.; Maclean, K.H.; Allard, D.; Barraclough, R.; Gilbertson, R.J. ERBB2 up-regulates S100A4 and several other prometastatic genes in medulloblastoma. Cancer Res., 2003, 63(1), 140-148.
85. Ferretti, E.; Di Marcotullio, L.; Gessi, M.; Mattei, T.; Greco, A.; Po, A.; De Smaele, E.; Giangaspero, F.; Riccardi, R.; Di Rocco, C.; Pazzaglia, S.; Maroder, M.; Alimandi, M.; Screpanti, I.; Gulino, A. Alternative splicing of the ErbB-4 cytoplasmic domain and its regulation by hedgehog signaling identify distinct medulloblastoma subsets. Oncogene, 2006, 25(55), 7267-7273.
86. Gilbertson, R.J.; Perry, R.H.; Kelly, P.J.; Pearson, A.D.; Lunec, J. Prognostic significance of her2 and her4 coexpression in childhood medulloblastoma. Cancer Res., 1997, 57, 3272-3280.
87. Elenius, K.; Choi, C.J.; Paul, S.; Santiestevan, E.; Nishi, E.; Klagsbrun, M. Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase. Oncogene, 1999, 18(16), 2607-2615.
88. Sell, C.; Rubini, M.; Rubin, R.; Liu, J.P.; Efstratiadis, A.; Baserga, R. Simian virus 40 large tumor antigen is unable to transform mouse embryonic fibroblasts lacking type 1 insulin-like growth factor receptor. Proc. Natl. Acad. Sci. USA, 1993, 90(23), 11217-11221.
89. Carboni, J.M.; Lee, A.V.; Hadsell, D.L.; Rowley, B.R.; Lee, F.Y.; Bol, D.K.; Camuso, A.E.; Gottardis, M.; Greer, A.F.; Ho, C.P.; Hurlburt, W.; Li, A.; Saulnier, M.; Velaparthi, U.; Wang, C.; Wen, M.L.; Westhouse, R.A.; Wittman, M.; Zimmermann, K.; Rupnow, B.A.; Wong, T.W. Tumor development by transgenic expression of a constitutively active insulin-like growth factor I receptor. Cancer Res., 2005, 65(9). 3781-3787.
90. Lopez, T.; Hanahan, D. Elevated levels of IGF-1 receptor convey invasive and metastatic capability in a mouse model of pancreatic islet tumorigenesis. Cancer Cell, 2002, 1(4), 339-353.
91. Yakar, S.; Leroith, D.; Brodt, P. The role of the growth hormone/insulin-like growth factor axis in tumor growth and progression: Lessons from animal models. Cytokine Growth Factor Rev., 2005, 16(4-5), 407-420.
92. Del Valle, L.; Enam, S.; Lassak, A.; Wang, J.Y.; Croul, S.; Khalili, K.; Reiss, K. Insulin-like growth factor I receptor activity in human medulloblastomas. Clin. Cancer Res., 2002, 8, 1822-1830.
93. Ogino, S.; Kubo, S.; Abdul-Karim, F.W.; Cohen, M.L. Comparative immunohistochemical study of insulin-like growth factor II and insulin-like growth factor receptor type 1 in pediatric brain tumors. Pediatr. Dev. Pathol., 2001, 4(1), 23-31.
94. Hartmann, W.; Koch, A.; Brune, H.; Waha, A.; Schüller, U.; Dani, I.; Denkhaus, D.; Langmann, W.; Bode, U.; Wiestler, O.D.; Schilling, K.; Pietsch, T. Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells. Am. J. Pathol., 2005, 166(4), 1153-1162.
95. Patti, R.; Reddy, C.D.; Geoerger, B.; Grotzer, M.A.; Raghunath, M.; Sutton, L.N.; Phillips, P.C. Autocrine secreted insulin-like growth factor-I stimulates MAP kinase-dependent mitogenic effects in human primitive neuroectodermal tumor/medulloblastoma. Int. J. Oncol., 2000, 16(3), 577-584.
96. Hahn, H.; Wojnowski, L.; Specht, K.; Kappler, R.; Calzada-Wack, J.; Potter, D.; Zimmer, A.; Müller, U.; Samson, E.; Quintanilla-Martinez, L.; Zimmer, A. Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosarcoma. J. Biol. Chem., 2000, 275(37), 28341-28344.
97. Wang, J.Y.; Del Valle, L.; Gordon, J.; Rubini, M.; Romano, G.; Croul, S.; Peruzzi, F.; Khalili, K.; Reiss, K. Activation of the IGF-IR system contributes to malignant growth of human and mouse medulloblastomas. Oncogene, 2001, 20(29), 3857-3868.
98. Haluska, P.; Shaw, H.M.; Batzel, G.N.; Yin, D.; Molina, J.R.; Molife, L.R.; Yap, T.A.; Roberts, M.L.; Sharma, A.; Gualberto, A.; Adjei, A.A.; de Bono, J.S. Phase I dose escalation study of the anti insulinlike growth factor-I receptor monoclonal antibody CP-751,871 in patients with refractory solid tumors. Clin. Cancer Res., 2007, 13, 5834-5840.
99. Karp, D.D.; Paz-Ares, L.G.; Novello, S.; Haluska, P.; Garland, L.; Cardenal, F.; Blakely, L.J.; Eisenberg, P.D.; Gualberto, A.; Langer, C.J. High activity of the anti-IGF-IR antibody CP-751,871 in combination with paclitaxel and carboplatin in squamous NSCLC. J. Clin. Oncol., 2008, 26, 8015.
100. Weroha, S.J.; Haluska, P. IGF-1 receptor inhibitors in clinical trials-early lessons. J. Mammary Gland Biol. Neoplasia, 2008, 13(4), 471-483.
101. Gilbertson, R.J.; Clifford, S.C. PDGFRB is overexpressed in metastatic medulloblastoma. Nat. Genet., 2003, 35(3), 197-198.
102. Edling, C.E.; Hallberg, B. c-Kit-a hematopoietic cell essential receptor tyrosine kinase. Int. J. Biochem. Cell Biol., 2007, 39(11), 1995-1998.
103. Chilton-Macneill, S.; Ho, M.; Hawkins, C.; Gassas, A.; Zielenska, M.; Baruchel, S. C-kit expression and mutational analysis in medulloblastoma. Pediatr. Dev. Pathol., 2004, 7(5), 493-498.
104. Demetri, G.D. Targeting the molecular pathophysiology of gastrointestinal stromal tumors with imatinib. Mechanisms, successes, and challenges to rational drug development. Hematol. Oncol. Clin. North Am., 2002, 16(5), 1115-1124.
105. Abouantoun, T.J.; MacDonald, T.J. Imatinib blocks migration and invasion of medulloblastoma cells by concurrently inhibiting activation of platelet-derived growth factor receptor and transactivation of epidermal growth factor receptor. Mol. Cancer Ther., 2009, 8, 1137-1147.
106. MacDonald, T.J.; Brown, K.M.; LaFleur, B.; Peterson, K.; Lawlor, C.; Chen, Y.; Packer, R.J.; Cogen, P.; Stephan, D.A. Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat. Genet., 2001, 29(2), 143-152.[Erratum in: Nat. Genet., 2003, 35(3), 287].
107. Gilbertson, R.J.; Langdon, J.A.; Hollander, A.; Hernan, R.; Hogg, T.L.; Gajjar, A.; Fuller, C.; Clifford, S.C. Mutational analysis of PDGFR-RAS/MAPK pathway activation in childhood medulloblastoma. Eur. J. Cancer, 2006, 42(5), 646-649.
108. Downward, J. Targeting RAS signalling pathways in cancer therapy. Nat. Rev. Cancer, 2003, 3(1), 11-22.
109. Pietras, K.; Sjöblom, T.; Rubin, K.; Heldin, C.H.; Östman, A. PDGF receptors as cancer drug targets. Cancer Cell, 2003, 3(5), 439-443.
110. Henriksson, M.; Lüscher, B. Proteins of the Myc network: essential regulators of cell growth and differentiation. Adv. Cancer Res., 1996, 68, 109-182.
111. Bishop, J.M. The molecular genetics of cancer. Science, 1987, 235(4786), 305-311.
112. Guérin, M.; Barrois, M.; Terrier, M.J.; Spielmann, M.; Riou, G. Overexpression of either c-myc or c-erbB-2/neu proto-oncogenes in human breast carcinomas: correlation with poor prognosis. Oncogene Res., 1988, 3(1), 21-31.
113. Kohl, N.E.; Kanda, N.; Schreck, R.R.; Bruns, G.; Latt, S.A; Gilbert, F.; Alt. F.W. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell, 1983, 35, 359-367.
114. Schwab, M.; Alitalo, K.; Klempnauer, K.H.; Varmus, H.E.; Bishop, J.M.; Gilbert, F.; Brodeur, G.; Goldstein, M.; Trent, J. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature, 1983, 305, 245-248.
115. Nau, M.M.; Brooks, B.J.; Battey, J.; Sausville, E.; Gazdar, A.F.; Kirsch, I.R.; McBride, O.W.; Bertness, V.; Hollis, G.F.; Minna, J.D. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature, 1985, 318(6041), 69-73.
116. Pfister, S.; Remke, M.; Benner, A.; Mendrzyk, F.; Toedt, G.; Felsberg, J.; Wittmann, A.; Devens, F.; Gerber, N.U.; Joos, S.; Kulozik, A.; Reifenberger, G.; Rutkowski, S.; Wiestler, O.D.; Radlwimmer, B.; Scheurlen, W.; Lichter, P.; Korshunov, A. Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci. J. Clin. Oncol., 2009, 27(10), 1627-1636.
117. Stearns, D.; Chaudhry, A.; Abel, T.W.; Burger, P.C.; Dang, C.V.; Eberhart, C.G. c-myc overexpression causes anaplasia in medulloblastoma. Cancer Res., 2006, 66(2), 673-681.
118. Rao, G.; Pedone, C.A.; Coffin, C.M.; Holland, E.C.; Fults, D.W. cmyc enhances sonic hedgehog-induced medulloblastoma formation from nestin-expressing neural progenitors in mice. Neoplasia, 2003, 5(3), 198-204.
119. Thomas, W.D.; Chen, J.; Gao, Y.R.; Cheung, B.; Koach, J.; Sekyere, E.; Norris, M.D.; Haber, M.; Ellis, T.; Wainwright, B.; Marshall, G.M. Patched1 deletion increases N-myc protein stability as a mechanism of medulloblastoma initiation and progression. Oncogene, 2009, 28(13), 1605-1615.
120. Vita, M.; Henriksson, M. The Myc oncoprotein as a therapeutic target for human cancer. Semin. Cancer Biol., 2006, 16(4), 318-330.
121. Johnsen, J.I.; Kogner, P.; Albihn, A.; Henriksson, M.A. Embryonal neural tumours and cell death. Apoptosis, 2009, 14(4), 424-438.
122. Soucek, L.; Whitfield, J.; Martins, C.P.; Finch, A.J.; Murphy, D.J.; Sodir, N.M.; Karnezis, A.N.; Swigart, L.B.; Nasi, S.; Evan, G.I. Modelling Myc inhibition as a cancer therapy. Nature, 2008, 455(7213), 679-683.
123. Berg, T.; Cohen, S.B.; Desharnais, J.; Sonderegger, C.; Maslyar, D.J.; Goldberg, J.; Boger, D.L.; Vogt, P.K. Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts. Proc. Natl. Acad. Sci. USA, 2002, 99(6), 3830-3835.
124. Yin, X.; Giap, C.; Lazo, J.S.; Prochownik, E.V. Low molecular weight inhibitors of Myc-Max interaction and function. Oncogene, 2003, 22(40), 6151-6159.
125. Mo, H.; Henriksson, M. Identification of small molecules that induce apoptosis in a Myc-dependent manner and inhibit Myc-driven transformation. Proc. Natl. Acad. Sci. USA, 2006, 103(16), 6344-6349.
126. Mo, H.; Vita, M.; Crespin, M.; Henriksson, M. Myc overexpression enhances apoptosis induced by small molecules. Cell Cycle, 2006, 5(19), 2191-2194.
127. Xu, Y.; Shi, J.; Yamamoto, N.; Moss, J.A.; Vogt, P.K.; Janda, K.D. A credit-card library approach for disrupting protein-protein interactions. Bioorg. Med. Chem., 2006, 14(8), 2660-2673.
128. Lu, X.; Pearson, A.; Lunec, J. The MYCN oncoprotein as a drug development target. Cancer Lett., 2003, 197(1-2), 125-130.
129. Huang, M.J.; Cheng, Y.C.; Liu, C.R.; Lin, S.; Liu, H.E. A smallmolecule c-myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Exp. Hematol., 2006, 34(11), 1480-1489.
130. Lin, C.P.; Liu, J.D.; Chow, J.M.; Liu, C.R.; Liu, H.E. Small-molecule c-myc inhibitor, 10058-F4, inhibits proliferation, downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells. Anticancer Drugs, 2007, 18(2), 161-170.
131. Wang, H.; Hammoudeh, D.I.; Follis, A.V.; Reese, B.E.; Lazo, J.S.; Metallo, S.J.; Prochownik, E.V. Improved low molecular weight Myc-Max inhibitors. Mol. Cancer Ther., 2007, 6(9), 2399-2408.
132. Guo, J.; Parise, R.A.; Joseph, E.; Egorin, M.J.; Lazo, J.S.; Prochownik, E.V.; Eiseman, J.L. Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice. Cancer Chemother. Pharmacol., 2009, 63(4), 615-625.
133. Chang, Q.; Chen, Z.; You, J.; McNutt, M.A.; Zhang, T.; Han, Z.; Zhang, X.; Gong, E.; Gu, J. All-trans-retinoic acid induces cell growth arrest in a human medulloblastoma cell line. J. Neurooncol., 2007, 84(3), 263-267.
134. Hallahan, A.R.; Pritchard, J.I. Chandraratna, R.A.; Ellenbogen, R.G.; Geyer, J.R.; Overland, R.P.; Strand, A.D.; Tapscott, S.J.; Olson, J.M. BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect. Nat. Med., 2003, 9(8), 1033-1038.
135. Gumireddy, K.; Sutton, L.N.; Phillips, P.C.; Reddy, C.D. All-transretinoic acid-induced apoptosis in human medulloblastoma: activation of caspase-3/poly(ADP-ribose) polymerase 1 pathway. Clin. Cancer Res., 2003, 9(11), 4052-4059.
136. Liu, J.; Guo, L.; Luo, Y.; Li, J.W.; Li, H. All trans-retinoic acid suppresses in vitro growth and down-regulates LIF gene expression as well as telomerase activity of human medulloblastoma cells. Anticancer Res., 2000, 20(4), 2659-2664.
137. Read, A.P.; Strachan, T. Cancer Genetics. Chapter 18, In: Human Molecular Genetics 2. Wiley; New York, 1999.
138. Saylors, R.L., 3rd.; Sidransky, D.; Friedman, H.S.; Bigner, S.H.; Bigner, D.D.; Vogelstein, B.; Brodeur, G.M. Infrequent p53 gene mutations in medulloblastomas. Cancer Res., 1991, 51(17), 4721-4723.
139. Badiali, M.; Iolascon, A.; Loda, M.; Scheithauer, B.W.; Basso, G.; Trentini, G.P.; Giangaspero, F. p53 gene mutations in medulloblastoma. Immunohistochemistry, gel shift analysis, and sequencing. Diagn. Mol. Pathol., 1993, 2(1), 23-28.
140. Adesina, A.M.; Nalbantoglu, J.; Cavenee, W.K. p53 gene mutation and mdm2 gene amplification are uncommon in medulloblastoma. Cancer Res., 1994, 54(21), 5649-5651.
141. Wang, W.; Kumar, P.; Wang, W.; Whalley, J.; Schwarz, M.; Malone, G.; Haworth, A.; Kumar, S. The mutation status of PAX3 and p53 genes in medulloblastoma. Anticancer Res., 1998, 18(2A), 849-853.
142. Wetmore, C.; Eberhart, D.E.; Curran, T. Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched. Cancer Res., 2001, 61(2), 513-516.
143. Burnett, M.E.; White, E.C.; Sih, S.; von Haken, M.S.; Cogen, P.H.Chromosome arm 17p deletion analysis reveals molecular genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumors of the central nervous system. Cancer Genet. Cytogenet., 1997, 97(1), 25-31.
144. Ray, A.; Ho, M.; Ma, J.; Parkes, R.K.; Mainprize, T.G.; Ueda, S.; McLaughlin, J.; Eric Bouffet, E.; James T.; Rutka, J.T.; Hawkins, C.E. A clinicobiological model predicting survival in medulloblastoma. Clin. Cancer Res., 2004, 10(22), 7613-7620.
145. Kato, J.Y.; Matsuoka, M.; Polyak, K.; Massagué, J.; Sherr, C.J. Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation. Cell, 1994, 79(3), 487-496.
146. Harada, H.; Becknell, B.; Wilm, M.; Mann, M.; Huang, L.J.; Taylor, S.S.; Scott, J.D.; Korsmeyer, S.J. Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A. Mol. Cell, 1999, 3(4), 413-422.
147. Lelievre, V.; Seksenyan, A.; Nobuta, H.; Yong, W.H.; Chhith, S.; Niewiadomski, P.; Cohen, J.R.; Dong, H.; Flores, A.; Liau, L.M.; Kornblum, H.I.; Scott, M.P.; Waschek, J.A. Disruption of the PACAP gene promotes medulloblastoma in ptc1 mutant mice. Dev. Biol., 2008, 313(1), 359-370.
148. Yang, L.; Jackson, E.; Woerner, B.M.; Perry, A.; Piwnica-Worms, D.; Rubin, J.B.Blocking CXCR4-mediated cyclic AMP suppression inhibits brain tumor growth in vivo. Cancer Res., 2007, 67(2), 651-658.
149. Schmidt, A.L.; de Farias, C.B.; Abujamra, A.L.; Kapczinski, F., Schwartsmann, G.; Brunetto, A.L.; Roesler, R. BDNF and PDE4, but not the GRPR, regulate viability of human medulloblastoma cells. J. Mol. Neurosci., 2010, 40(3), 303-310.
150. Goldhoff, P.; Warrington, N.M.; Limbrick, D.D. Jr; Hope, A.; Woerner, B.M.; Jackson, E.; Perry, A.; Piwnica-Worms, D.; Rubin, J.B. Targeted inhibition of cyclic AMP phosphodiesterase-4 promotes brain tumor regression. Clin. Cancer Res., 2008, 14, 7717-7725.
151. Hartmann, W.; Digon-Söntgerath, B.; Koch, A.; Waha, A.; Endl, E.; Dani, I.; Denkhaus, D.; Goodyer, C.G.; Sörensen, N.; Wiestler, O.D.; Pietsch, T. Phosphatidylinositol 3¢-kinase/AKT signaling is activated in medulloblastoma cell proliferation and is associated with reduced expression of PTEN. Clin. Cancer Res., 2006, 12(10), 3019-3027.
152. Włodarski, P.; Grajkowska, W.;Łojek, M.; Rainko, K.; Jóźwiak, J. Activation of Akt and Erk pathways in medulloblastoma. Folia Neuropathol., 2006, 44(3), 214-220.
153. Patapoutian, A.; Reichardt, L.F. Trk receptors: mediators of neurotrophin action. Curr. Opin. Neurobiol., 2001, 11(3), 272-280.
154. McCall, T.D.; Pedone, C.A.; Fults, D.W. Apoptosis suppression by somatic cell transfer of Bcl-2 promotes Sonic hedgehog-dependent medulloblastoma formation in mice. Cancer Res., 2007, 67(11), 5179-5185.
155. Hambardzumyan, D.; Becher, O.J.; Rosenblum, M.K.; Pandolfi, P.P.; Manova-Todorova, K.; Holland, E.C. PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo. Genes Dev., 2008, 22, 436-448.
156. Lauth, M.; Bergström, A.; Shimokawa, T.; Toftgård, R. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc. Natl. Acad. Sci. USA, 2007, 104(20), 8455-8460.
157. Aifa, S.; Rebai, A. ErbB antagonists patenting: playing chess with cancer. Recent Pat. Biotechnol., 2008, 2(3), 181-187.
158. Entz-Werle, N.; Velasco, V.; Neuville, A.; Geoerger, B.; Mathieu, M.C.; Guerin, E.; Kehrli, P.; Gaub, M.P.; Vassal, G.; Grill, J. Do medulloblastoma tumors meet the Food and Drug Administration criteria for anti-erbB2 therapy with trastuzumab? Pediatr. Blood Cancer, 2008, 50(1), 163-166.
159. Yang, F.; Van Meter, T.E.; Buettner, R.; Hedvat, M.; Liang, W.; Kowolik, C.M.; Mepani, N.; Mirosevich, J.; Nam, S.; Chen, M.Y.; Tye, G.; Kirschbaum, M.; Jove, R. Sorafenib inhibits signal transducer and activator of transcription 3 signaling associated with growth arrest and apoptosis of medulloblastomas. Mol. Cancer Ther., 2008, 7(11), 3519-3526.
160. Capdeville, R.; Buchdunger, E.; Zimmermann, J.; Matter, A. Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat. Rev. Drug Discov., 2002, 1(7), 493-502.
161. Abouantoun, T.J.; MacDonald, T.J. Imatinib blocks migration and invasion of medulloblastoma cells by concurrently inhibiting activation of platelet-derived growth factor receptor and transactivation of epidermal growth factor receptor. Mol. Cancer Ther., 2009, 8, 1137-1147.
162. Östman, A.; Heldin, C.H. Involvement of platelet-derived growth factor in disease: development of specific antagonists. Adv. Cancer Res., 2001, 80, 1-38.
163. Mendel, D.B.; Laird, A.D.; Xin, X.; Louie, S.G.; Christensen, J.G.; Li, G.; Schreck, R.E.; Abrams, T.J.; Ngai, T.J.; Lee, L.B.; Murray, L.J.; Carver, J.; Chan, E.; Moss, K.G.; Haznedar, J.O.; Sukbuntherng, J.; Blake, R.A.; Sun, L.; Tang, C.; Miller, T.; Shirazian, S.; McMahon, G.; Cherrington, J.M. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin. Cancer Res., 2003, 9(1), 327-337.
164. Rixe, O.; Bukowski, R.M.; Michaelson, M.D.; Wilding, G.; Hudes, G.R.; Bolte, O.; Motzer, R.J.; Bycott, P.; Liau, K.F.; Freddo, J.; Trask, P.C.; Kim, S.; Rini, B.I. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol., 2007, 8(11), 975-984.
165. End, D.W.; Smets, G.; Todd, A.V.; Applegate, T.L.; Fuery, C.J.; Angibaud, P.; Venet, M.; Sanz, G.; Poignet, H.; Skrzat, S.; Devine, A.; Wouters, W.; Bowden C. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res., 2001, 61(1), 131-137.
166. Sebolt-Leopold, J.S.; Dudley, D.T.; Herrera, R.; Van Becelaere, K.; Wiland, A.; Gowan, R.C.; Tecle, H.; Barrett, S.D.; Bridges, A.; Przybranowski, S.; Leopold, W.R.; Saltiel, A.R. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat. Med., 1999, 5(7), 810-816.
167. Yap, T.A.; Garrett, M.D.; Walton, M.I.; Raynaud, F.; de Bono, J.S.; Workman, P. Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr. Opin. Pharmacol., 2008, 8(4), 393-412.
168. Collins, I. Targeted small-molecule inhibitors of Protein Kinase B as anticancer agents. Med. Chem., 2009, 9(1), 32-50.
169. Dancey, J.; Sausville, E.A. Issues and progress with protein kinase inhibitors for cancer treatment. Nat. Rev. Drug Discov., 2003, 2, 296-313.
170. Miller, T.W.; Forbes, J.T.; Shah, C.; Wyatt, S.K.; Manning, H.C.; Olivares, M.G.; Sanchez, V.; Dugger, T.C.; de Matos Granja, N.; Narasanna, A.; Cook, R.S.; Kennedy, J.P.; Lindsley, C.W.; Arteaga, C.L. Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells. Clin. Cancer Res., 2009, 15(23), 7266-7276.
171. Fan, Q.W.; Cheng, C.; Knight, Z.A.; Haas-Kogan, D.; Stokoe, D.; James, C.D.; McCormick, F.; Shokat, K.M.; Weiss, W.A. EGFR signals to mTOR through PKC and independently of Akt in glioma. Sci. Signal., 2009, 2(55), ra4.
172. Goudar, R.K.; Shi, Q.; Hjelmeland, M.D.; Keir, S.T.; McLendon, R.E.; Wikstrand, C.J.; Reese, E.D.; Conrad, C.A.; Traxler, P.; Lane, H.A.; Reardon, D.A.; Cavenee, W.K.; Wang, X.F.; Bigner, D.D.; Friedman, H.S.; Rich, J.N. Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamycin (RAD001) offers improved glioblastoma tumor growth inhibition. Mol. Cancer Ther., 2005, 4(1), 101-112.
173. Galanis, E.; Buckner, J.C.; Maurer, M.J.; Kreisberg, J.I.; Ballman, K.; Boni, J.; Peralba, J.M.; Jenkins, R.B.; Dakhil, S.R.; Morton, R.F.; Jaeckle, K.A.; Scheithauer, B.W.; Dancey, J.; Hidalgo, M.; Walsh, D.J. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J. Clin. Oncol., 2005, 23(23), 5294-5304.
174. Haluska, P.; Shaw, H.; Batzel, G.N.; Molife, L.R.; Adjei, A.A.; Yap, T.A.; Roberts, M.L.; Gualberto, A.; de Bono, J.S. Phase I dose escalation study of the anti-IGF-IR monoclonal antibody CP-751,871 in patients with refractory solid tumors. ASCO Annu. Meeting Proc. Part I, 2007, 25(18S), 3586.
175. Northcott, P.A.; Nakahara, Y.; Wu, X.; Feuk, L.; Ellison, D.W.; Croul, S.; Mack, S.; Kongkham, P.N.; Peacock, J.; Dubuc, A.; Ra, Y.S.; Zilberberg, K.; McLeod, J.; Scherer, S.W.; Sunil Rao, J.; Eberhart, C.G.; Grajkowska, W.; Gillespie, Y.; Lach, B.; Grundy, R.; Pollack, I.F.; Hamilton, R.L.; Van Meter, T.; Carlotti, C.G.; Boop, F.; Bigner, D.; Gilbertson, R.J.; Rutka, J.T.; Taylor, M.D. Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nat. Genet., 2009, 41(4), 465-472.
176. Sonnemann, J.; Kumar, K.S.; Heesch, S.; Müller, C.; Hartwig, C.; Maass, M.; Bader, P.; Beck, J.F. Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells. Int. J. Oncol., 2006, 28(3), 755-766.
177. Li, X.N.; Shu, Q.; Su, J.M.; Perlaky, L.; Blaney, S.M.; Lau, C.C. Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC. Mol. Cancer Ther., 2005, 4(12), 1912-1922.
178. Shu, Q.; Antalffy, B.; Su, J.M.; Adesina, A.; Ou, C.N.; Pietsch, T.; Blaney, S.M.; Lau, C.C.; Li, X.N. Valproic Acid prolongs survival time of severe combined immunodeficient mice bearing intracerebellar orthotopic medulloblastoma xenografts. Clin. Cancer Res., 2006, 12(15), 4687-4694.
179. Spiller, S.E.; Ditzler, S.H.; Pullar, B.J.; Olson, J.M. Response of preclinical medulloblastoma models to combination therapy with 13-cis retinoic acid and suberoylanilide hydroxamic acid (SAHA). J. Neurooncol., 2008, 87(2), 133-141.
180. Su, X.; Gopalakrishnan, V.; Stearns, D.; Aldape, K.; Lang, F.F.; Fuller, G.; Snyder, E.; Eberhart, C.G.; Majumder, S. Abnormal expression of REST/NRSF and Myc in neural stem/progenitor cells causes cerebellar tumors by blocking neuronal differentiation. Mol. Cell Biol., 2006, 26(5), 1666-1678.
181. Kagalwala, M.N.; Singh, S.K.; Majumder, S. Stemness is only a state of the cell. Cold Spring Harb. Symp. Quant. Biol., 2008, 73, 227-234.
182. Fuller, G.N.; Su, X.; Price, R.E.; Cohen, Z.R.; Lang, F.F.; Sawaya, R.; Majumder, S. Many human medulloblastoma tumors overexpress repressor element-1 silencing transcription (REST)/neuron-restrictive silencer factor, which can be functionally countered by REST-VP16. Mol. Cancer Ther., 2005, 4(3), 343-349.
183. Damodar, R.C.; Guttapalli, A.; Adamson, P.C.; Vemuri, M.C.; O'Rourke, D.; Sutton, L.N.; Phillips, P.C. Anticancer effects of fenretinide in human medulloblastoma. Cancer Lett., 2006, 231(2), 262-269.