Deregulated signalling networks in human brain tumours

Biochimica et Biophysica Acta - Proteins and Proteomics

Volumn 1804, Issue 3, 2010, Pages 476-483

  Grzmil, Michal ^a   Hemmings, Brian A ^a  

^a FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH   (Switzerland)

Author keywords

Glioblastoma; Kinase inhibitor; Signalling pathways

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; 2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; 4 DIALLYLAMINOMETHYLENE 1,3,4,7,10,11,12,13,14,15,16,17 DODECAHYDRO 6 HYDROXY 1 METHOXYMETHYL 10,13 DIMETHYL 3,7,17 TRIOXO 2 OXACYCLOPENTA[A]PHENANTHREN 11 YL ACETATE; 6 [4 (4 ETHYL 1 PIPERAZINYLMETHYL)PHENYL] 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; CETUXIMAB; DASATINIB; ENZASTAURIN; ERLOTINIB; EVEROLIMUS; GEFITINIB; IMATINIB; LAPATINIB; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; PAZOPANIB; PERIFOSINE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN KINASE C; RAPAMYCIN; RAS PROTEIN; SORAFENIB; TANDUTINIB; TEMOZOLOMIDE; TEMSIROLIMUS; VANDETANIB;

BRAIN CANCER; CANCER GRADING; CANCER GROWTH; CANCER SURVIVAL; CARCINOGENESIS; CELL ACTIVATION; CELL CYCLE PROGRESSION; CLINICAL TRIAL; DRUG TARGETING; GENE OVEREXPRESSION; GLIOBLASTOMA; HUMAN; MONOTHERAPY; MUTATION; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

BRAIN NEOPLASMS; ENZYME ACTIVATION; GLIOBLASTOMA; HUMANS; NEOPLASM PROTEINS; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; SIGNAL TRANSDUCTION;

EID: 75349095750     PISSN: 15709639     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbapap.2009.10.018     Document Type: Review

References (102)

1. CBTRUS. Statistical report: primary brain tumors in the United States, 1998-2002. Central Brain Tumor Registry of the United States, Hinsdale, IL, USA (2005)
2. Grossman S.A., and Batara J.F. Current management of glioblastoma multiforme. Semin. Oncol. 31 (2004) 635-644
3. Ohgaki H., Dessen P., Jourde B., Horstmann S., Nishikawa T., Di Patre P.L., Burkhard C., Schüler D., Probst-Hensch N.M., Maiorka P.C., Baeza N., Pisani P., Yonekawa Y., Yasargil M.G., Lütolf U.M., and Kleihues P. Genetic pathways to glioblastoma: a population-based study. Cancer Res. 64 (2004) 6892-6899
4. Stupp R., Mason W.P., van den Bent M.J., Weller M., Fisher B., Taphoorn M.J., Belanger K., Brandes A.A., Marosi C., Bogdahn U., Curschmann J., Janzer R.C., Ludwin S.K., Gorlia T., Allgeier A., Lacombe D., Cairncross J.G., Eisenhauer E., and Mirimanoff R.O. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352 (2005) 987-996
5. Taphoorn M.J., Stupp R., Coens C., Osoba D., Kortmann R., van den Bent M.J., Mason W., Mirimanoff R.O., Baumert B.G., Eisenhauer E., Forsyth P., and Bottomley A. Health-related quality of life in patients with glioblastoma: a randomised controlled trial. Lancet Oncol. 6 (2005) 937-944
6. Gerson S.L. Clinical relevance of MGMT in the treatment of cancer. J. Clin. Oncol. 20 (2002) 2388-2399
7. Hegi M.E., Liu L., Herman J.G., Stupp R., Wick W., Weller M., Mehta M.P., and Gilbert M.R. Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J. Clin. Oncol. 26 (2008) 4189-4199
8. Everhard S., Kaloshi G., Crinière E., Benouaich-Amiel A., Lejeune J., Marie Y., Sanson M., Kujas M., Mokhtari K., Hoang-Xuan K., Delattre J.Y., and Thillet J. MGMT methylation: a marker of response to temozolomide in low-grade gliomas. Ann. Neurol. 60 (2006) 740-743
9. Louis D.N., Ohgaki H., Wiestler O.D., Cavenee W.K., Burger P.C., Jouvet A., Scheithauer B.W., and Kleihues P. The 2007 WHO classification of tumours of the central nervous system (2007), IARC Press, Lyon, France
10. Arjona D., Rey J.A., and Taylor S.M. Early genetic changes involved in low-grade astrocytic tumor development. Curr. Mol. Med. 6 (2006) 645-650
11. Furnari F.B., Fenton T., Bachoo R.M., Mukasa A., Stommel J.M., Stegh A., Hahn W.C., Ligon K.L., Louis D.N., Brennan C., Chin L., DePinho R.A., and Cavenee W.K. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 21 (2007) 2683-2710
12. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455 (2008) 1061-1068
13. Parsons D.W., Jones S., Zhang X., Lin J.C., Leary R.J., Angenendt P., Mankoo P., Carter H., Siu I.M., Gallia G.L., Olivi A., McLendon R., Rasheed B.A., Keir S., Nikolskaya T., Nikolsky Y., Busam D.A., Tekleab H., Diaz L.A., Hartigan J., Smith D.R., Strausberg R.L., Marie S.K., Shinjo S.M., Yan H., Riggins G.J., Bigner D.D., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E., and Kinzler K.W. An integrated genomic analysis of human glioblastoma multiforme. Science 321 (2008) 1807-1812
14. Maher E.A., Furnari F.B., Bachoo R.M., Rowitch D.H., Louis D.N., Cavenee W.K., and DePinho R.A. Malignant glioma: genetics and biology of a grave matter. Genes Dev. 15 (2001) 1311-1333
15. Chakravarti A., Dicker A., and Mehta M. The contribution of epidermal growth factor receptor (EGFR) signaling pathway to radioresistance in human gliomas: a review of preclinical and correlative clinical data. Int. J. Radiat. Oncol. Biol. Phys. 58 (2004) 927-931
16. Sonabend A.M., Dana K., and Lesniak M.S. Targeting epidermal growth factor receptor variant III: a novel strategy for the therapy of malignant glioma. Genes Dev. 15 (2001) 1311-1333
17. Ramnarain D.B., Park S., Lee D.Y., Hatanpaa K.J., Scoggin S.O., Otu H., Libermann T.A., Raisanen J.M., Ashfaq R., Wong E.T., Wu J., Elliott R., and Habib A.A. Differential gene expression analysis reveals generation of an autocrine loop by a mutant epidermal growth factor receptor in glioma cells. Cancer Res. 66 (2006) 867-874
18. Weller M., Malipiero U., Aguzzi A., Reed J.C., and Fontana A. Protooncogene bcl-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation. J. Clin. Invest. 95 (1995) 2633-2643
19. Rieger L., Weller M., Bornemann A., Schabet M., Dichgans J., and Meyermann R. BCL-2 family protein expression in human malignant glioma: a clinical-pathological correlative study. J. Neurol. Sci. 155 (1998) 68-75
20. Nagane M., Levitzki A., Gazit A., Cavenee W.K., and Huang H.J. Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like proteases. Proc. Natl. Acad. Sci. U. S. A. 95 (1998) 5724-5729
21. Hermanson M., Funa K., Hartman M., Claesson-Welsh L., Heldin C.H., Westermark B., and Nistér M. Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res. 52 (1992) 3213-3219
22. Plate K.H., Breier G., Farrell C.L., and Risau W. Platelet-derived growth factor receptor-beta is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas. Lab. Invest. 67 (1992) 529-534
23. Di Rocco F., Carroll R.S., Zhang J., and Black P.M. Platelet-derived growth factor and its receptor expression in human oligodendrogliomas. Neurosurgery 42 (1998) 341-346
24. Hynes N.E., and MacDonald G. ErbB receptors and signaling pathways in cancer. Curr. Opin. Cell. Biol. 21 (2009) 177-184
25. Ross J.S., Slodkowska E.A., Symmans W.F., Pusztai L., Ravdin P.M., and Hortobagyi G.N. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 14 (2009) 320-368
26. Kim E.S., and Salgia R. MET pathway as a therapeutic target. J. Thorac. Oncol. 4 (2009) 444-447
27. Karamouzis M.V., Konstantinopoulos P.A., and Papavassiliou A.G. Targeting MET as a strategy to overcome crosstalk-related resistance to EGFR inhibitors. Lancet Oncol. 10 (2009) 709-717
28. Jensen R.L., Ragel B.T., Whang K., and Gillespie D. Inhibition of hypoxia inducible factor-1alpha (HIF-1alpha) decreases vascular endothelial growth factor (VEGF) secretion and tumor growth in malignant gliomas. J. Neurooncol. 78 (2006) 233-247
29. Sonoda Y., Kanamori M., Deen D.F., Cheng S.Y., Berger M.S., and Pieper R.O. Overexpression of vascular endothelial growth factor isoforms drives oxygenation and growth but not progression to glioblastoma multiforme in a human model of gliomagenesis. Cancer Res. 63 (2003) 1962-1968
30. Gomez-Manzano C., Fueyo J., Jiang H., Glass T.L., Lee H.Y., Hu M., Liu J.L., Jasti S.L., Liu T.J., Conrad C.A., and Yung W.K. Mechanisms underlying PTEN regulation of vascular endothelial growth factor and angiogenesis. Ann. Neurol. 53 (2003) 109-117
31. Yoshino Y., Aoyagi M., Tamaki M., Duan L., Morimoto T., and Ohno K. Activation of p38 MAPK and/or JNK contributes to increased levels of VEGF secretion in human malignant glioma cells. Int. J. Oncol. 29 (2006) 981-987
32. Saino M., Maruyama T., Sekiya T., Kayama T., and Murakami Y. Inhibition of angiogenesis in human glioma cell lines by antisense RNA from the soluble guanylate cyclase genes, GUCY1A3 and GUCY1B3. Oncol. Rep. 12 (2004) 47-52
33. Tsai J.C., Goldman C.K., and Gillespie G.Y. Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF. J. Neurosurg. 82 (1995) 864-873
34. Yan H., Parsons D.W., Jin G., McLendon R., Rasheed B.A., Yuan W., Kos I., Batinic-Haberle I., Jones S., Riggins G.J., Friedman H., Friedman A., Reardon D., Herndon J., Kinzler K.W., Velculescu V.E., Vogelstein B., and Bigner D.D. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 360 (2009) 765-773
35. Zhao S., Lin Y., Xu W., Jiang W., Zha Z., Wang P., Yu W., Li Z., Gong L., Peng Y., Ding J., Lei Q., Guan K.L., and Xiong Y. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science 324 (2009) 261-265
36. Gschwind A., Fischer O.M., and Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat. Rev. Cancer 4 (2004) 361-370
37. McKay M.M., and Morrison D.K. Integrating signals from RTKs to ERK/MAPK. Oncogene 26 (2007) 3113-3121
38. Guha A. Ras activation in astrocytomas and neurofibromas. Can. J. Neurol. Sci. 25 (1998) 267-281
39. Martin G.A., Viskoohil D., Bollag G., McCabe P.C., Crosier W.J., Haubruck H., Conroy L., Clark R., O'Connell P., Cawthon R.M., Innis M.A., and McCormick F. The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell 63 (1990) 843-849
40. Xu G., O'Connell P., Viskochil D., Cawthon R., Robertson M., Culver M., Dunn D., Stevens J., Gesteland R., White R., and Weiss R. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62 (1990) 599-608
41. McGillicuddy L.T., Fromm J.A., Hollstein P.E., Kubek S., Beroukhim R., De Raedt T., Johnson B.W., Williams S.M., Nghiemphu P., Liau L.M., Cloughesy T.F., Mischel P.S., Parret A., Seiler J., Moldenhauer G., Scheffzek K., Stemmer-Rachamimov A.O., Sawyers C.L., Brennan C., Messiaen L., Mellinghoff I.K., and Cichowski K. Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis. Cancer Cell. 16 (2009) 44-54
42. Hawkins P.T., Anderson K.E., Davidson K., and Stephens L.R. Signalling through Class I PI3Ks in mammalian cells. Biochem. Soc. Trans. 34 (2006) 647-662
43. Knobbe C.B., and Reifenberger G. Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-3′-kinase/protein kinase B (Akt) signal transduction pathway in glioblastomas. Brain Pathol. 13 (2003) 507-518
44. Maehama T., and Dixon J.E. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J. Biol. Chem. 73 (1998) 13375-13378
45. Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie R., Bigner S.H., Giovanella B.C., Ittmann M., Tycko B., Hibshoosh H., Wigler M.H., and Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275 (1997) 1943-1947
46. Boström J., Cobbers J.M., Wolter M., Tabatabai G., Weber R.G., Lichter P., Collins V.P., and Reifenberger G. Mutation of the PTEN (MMAC1) tumor suppressor gene in a subset of glioblastomas but not in meningiomas with loss of chromosome arm 10q. Cancer Res. 58 (1998) 29-33
47. Wiencke J.K., Zheng S., Jelluma N., Tihan T., Vandenberg S., Tamgüney T., Baumber R., Parsons R., Lamborn K.R., Berger M.S., Wrensch M.R., Haas-Kogan D.A., and Stokoe D. Methylation of the PTEN promoter defines low-grade gliomas and secondary glioblastoma. Neuro. Oncol. 9 (2007) 271-279
48. Fayard E., Tintignac L.A., Baudry A., and Hemmings B.A. Protein kinase B/Akt at a glance. J. Cell. Sci. 118 (2005) 5675-5678
49. Averous J., and Proud C.G. When translation meets transformation: the mTOR story. Oncogene 25 (2006) 6423-6435
50. Fan Q.W., and Weiss W.A. Isoform specific inhibitors of PI3 kinase in glioma. Cell. Cycle 20 (2006) 2301-2305
51. Angileri F.F., Aguennouz M., Conti A., La Torre D., Cardali S., Crupi R., Tomasello C., Germanò A., Vita G., and Tomasello F. Nuclear factor-kappaB activation and differential expression of survivin and Bcl-2 in human grade 2-4 astrocytomas. Cancer 112 (2008) 2258-2266
52. Wang H., Wang H., Zhang W., Huang H.J., Liao W.S., and Fuller G.N. Analysis of the activation status of Akt, NFkappaB, and Stat3 in human diffuse gliomas. Lab. Invest. 84 (2004) 941-951
53. Medema R.H., Kops G.J., Bos J.L., and Burgering B.M. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 404 (2000) 782-787
54. Seoane J., Le H.V., Shen L., Anderson S.A., and Massagué J. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 117 (2004) 211-223
55. Stegh A.H., Kim H., Bachoo R.M., Forloney K.L., Zhang J., Schulze H., Park K., Hannon G.J., Yuan J., Louis D.N., DePinho R.A., and Chin L. Bcl2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma. Genes Dev. 21 (2007) 98-111
56. da Rocha A.B., Mans D.R., Regner A., and Schwartsmann G. Targeting protein kinase C: new therapeutic opportunities against high-grade malignant gliomas?. Oncologist 7 (2002) 17-33
57. Aeder S.E., Martin P.M., Soh J.W., and Hussaini I.M. PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene 23 (2004) 9062-9069
58. Levine A.J., Hu W., and Feng Z. The P53 pathway: what questions remain to be explored?. Cell. Death Differ. 13 (2006) 1027-1036
59. Ohgaki H., and Kleihues P. Genetic pathways to primary and secondary glioblastoma. Am. J. Pathol. 170 (2007) 1445-1453
60. Shvarts A., Steegenga W.T., Riteco N., van Laar T., Dekker P., Bazuine M., van Ham R.C., van der Houven van Oordt W., Hateboer G., van der Eb A.J., and Jochemsen A.G. MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J. 15 (1996) 5349-5357
61. Riemenschneider M.J., Büschges R., Wolter M., Reifenberger J., Boström J., Kraus J.A., Schlegel U., and Reifenberger G. Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification. Cancer Res. 59 (1999) 6091-6096
62. Gu J., Kawai H., Nie L., Kitao H., Wiederschain D., Jochemsen A.G., Parant J., Lozano G., and Yuan Z.M. Mutual dependence of MDM2 and MDMX in their functional inactivation of p53. J. Biol. Chem. 277 (2002) 19251-19254
63. Linares L.K., Hengstermann A., Ciechanover A., Müller S., and Scheffner M. HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 12009-12014
64. Quelle D.E., Zindy F., Ashmun R.A., and Sherr C.J. Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell 83 (1995) 993-1000
65. Kamiryo T., Tada K., Shiraishi S., Shinojima N., Nakamura H., Kochi M., Kuratsu J., Saya H., and Ushio Y. Analysis of homozygous deletion of the p16 gene and correlation with survival in patients with glioblastoma multiforme. J. Neurosurg. 96 (2002) 815-822
66. Sharpless N.E. INK4a/ARF: a multifunctional tumor suppressor locus. Mutat. Res. 576 (2005) 22-38
67. Henson J.W., Schnitker B.L., Correa K.M., von Deimling A., Fassbender F., Xu H.J., Benedict W.F., Yandell D.W., and Louis D.N. The retinoblastoma gene is involved in malignant progression of astrocytomas. Ann. Neurol. 36 (1994) 714-721
68. Nakamura M., Yonekawa Y., Kleihues P., and Ohgaki H. Promoter hypermethylation of the RB1 gene in glioblastomas. Lab. Invest. 81 (2001) 77-82
69. Costello J.F., Plass C., Arap W., Chapman V.M., Held W.A., Berger M.S., Huang H.J.S., and Cavenee W.K. Cyclin-dependent kinase 6 (CDK6) amplification in human gliomas identified using two-dimensional separation of genomic DNA. Cancer Res. 57 (1997) 1250-1254
70. Lam P.Y., Di Tomaso E., Ng H.K., Pang J.C., Roussel M.F., and Hjelm N.M. Expression of p19INK4d, CDK4, CDK6 in glioblastoma multiforme. Br. J. Neurosurg. 14 (2000) 28-32
71. Büschges R., Weber R.G., Actor B., Lichter P., Collins V.P., and Reifenberger G. Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas. Brain Pathol. 9 (1999) 435-442
72. Sathornsumetee S., and Reardon D.A. Targeting multiple kinases in glioblastoma multiforme. Expert. Opin. Investig. Drugs 18 (2009) 277-292
73. Penas-Prado M., and Gilbert M.R. Molecularly targeted therapies for malignant gliomas: advances and challenges. Expert. Rev. Anticancer Ther. 7 (2007) 641-661
74. Chakravarti A., Tyndall E., Palanichamy K., Mehta M., Aldape K., and Loeffler J. Impact of molecular profiling on clinical trial design for glioblastoma. Curr. Oncol. Rep. 9 (2007) 71-79
75. Manning G., Whyte D.B., Martinez R., Hunter T., and Sudarsanam S. The protein kinase complement of the human genome. Science 298 (2002) 1912-1934
76. Wesche H., Xiao S.H., and Young S.W. High throughput screening for protein kinase inhibitors. Comb. Chem. High Throughput Screen 8 (2005) 181-195
77. Fischer H., Gottschlich R., and Seelig A. Blood-brain barrier permeation: molecular parameters governing passive diffusion. J. Membr. Biol. 165 (1998) 201-211
78. Pardridge W.M. Brain Drug Targeting; The Future of Brain Drug Development (2001), Cambridge University Press
79. Pardridge W.M. Drug targeting to the brain. Pharm. Res. 24 (2007) 1733-1744
80. Pardridge W.M. Molecular Trojan horses for blood-brain barrier drug delivery. Curr. Opin. Pharmacol. 6 (2006) 494-500
81. Stommel J.M., Kimmelman A.C., Ying H., Nabioullin R., Ponugoti A.H., Wiedemeyer R., Stegh A.H., Bradner J.E., Ligon K.L., Brennan C., Chin L., and DePinho R.A. Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318 (2007) 287-290
82. Lino M., and Merlo A. Translating biology into clinic: the case of glioblastoma. Curr. Opin. Cell. Biol. 21 (2009) 311-316
83. Mellinghoff I.K., Wang M.Y., Vivanco I., Haas-Kogan D.A., Zhu S., Dia E.Q., Lu K.V., Yoshimoto K., Huang J.H., Chute D.J., Riggs B.L., Horvath S., Liau L.M., Cavenee W.K., Rao P.N., Beroukhim R., Peck T.C., Lee J.C., Sellers W.R., Stokoe D., Prados M., Cloughesy T.F., Sawyers C.L., and Mischel P.S. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N. Engl. J. Med. 353 (2005) 2012-2024
84. 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., and 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. 4 (2005) 101-112
85. Thiessen B., Stewart C., Tsao M., Kamel-Reid S., Schaiquevich P., Mason W., Easaw J., Belanger K., Forsyth P., McIntosh L., and Eisenhauer E. A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation. Cancer Chemother. Pharmacol. 65 (2010) 353-361
86. Sathornsumetee S., Reardon D.A., Desjardins A., Quinn J.A., Vredenburgh J.J., and Rich J.N. Molecularly targeted therapy for malignant glioma. Cancer 110 (2007) 13-24
87. Fan Q.W., Knight Z.A., Goldenberg D.D., Yu W., Mostov K.E., Stokoe D., Shokat K.M., and Weiss W.A. A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell. 9 (2006) 341-349
88. Westhoff M.A., Kandenwein J.A., Karl S., Vellanki S.H., Braun V., Eramo A., Antoniadis G., Debatin K.M., and Fulda S. The pyridinylfuranopyrimidine inhibitor, PI-103, chemosensitizes glioblastoma cells for apoptosis by inhibiting DNA repair. Oncogene 28 (2009) 3586-3596
89. Belda-Iniesta C., Carpeno-Jde C., Saenz E.C., Gutierrez M., Perona R., and Baron M.G. Long term responses with cetuximab therapy in glioblastoma multiforme. Cancer Biol. Ther. 5 (2006) 912-914
90. Sandström M., Johansson M., Andersson U., Bergh A., Bergenheim A.T., and Henriksson R. The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model. Br. J. Cancer 91 (2004) 1174-1180
91. Sathornsumetee S., and Rich J.N. Vandetanib, a novel multitargeted kinase inhibitor, in cancer therapy. Drugs Today (Barc) 42 (2006) 657-670
92. Cheng Y., and Paz K. Tandutinib, an oral, small-molecule inhibitor of FLT3 for the treatment of AML and other cancer indications. IDrugs 11 (2008) 46-56
93. Dresemann G. Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: a patient series. Ann. Oncol. 16 (2005) 1702-1708
94. Jane E.P., Premkumar D.R., and Pollack I.F. Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. J. Pharmacol. Exp. Ther. 319 (2006) 1070-1080
95. Sloan B., and Scheinfeld N.S. Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy. Curr. Opin. Investig. Drugs 9 (2008) 1324-1335
96. Milano V., Piao Y., LaFortune T., and de Groot J. Dasatinib-induced autophagy is enhanced in combination with temozolomide in glioma. Mol. Cancer Ther. 8 (2009) 394-406
97. Howes A.L., Chiang G.G., Lang E.S., Ho C.B., Powis G., Vuori K., and Abraham R.T. The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures. Mol. Cancer Ther. 6 (2007) 2505-2514
98. Liu T.J., Koul D., LaFortune T., Tiao N., Shen R.J., Maira S.M., Garcia-Echevrria C., and Yung W.K. NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas. Mol. Cancer Ther. 8 (2009) 2204-2210
99. Momota H., Nerio E., and Holland E.C. Perifosine inhibits multiple signaling pathways in glial progenitors and cooperates with temozolomide to arrest cell proliferation in gliomas in vivo. Cancer Res. 65 (2005) 7429-7435
100. Guertin D.A., and Sabatini D.M. The pharmacology of mTOR inhibition. Sci. Signal. 2 (2009) 24
101. Rieger J., Lemke D., Maurer G., Weiler M., Frank B., Tabatabai G., Weller M., and Wick W. Enzastaurin-induced apoptosis in glioma cells is caspase-dependent and inhibited by BCL-XL. J. Neurochem. 106 (2008) 2436-2448
102. Thompson N., and Lyons J. Recent progress in targeting the Raf/MEK/ERK pathway with inhibitors in cancer drug discovery. Curr. Opin. Pharmacol. 5 (2005) 350-356