Malignant gliomas: strategies to increase the effectiveness of targeted molecular treatment

References

• Statistical report: primary brain tumors in the United States, 1998–2002. Central Brain Tumor Registry of the United States, (2005).
   Google Scholar
• World Health Organization classification of tumors. In: Pathology and Genetics of Tumours of the Nervous System. Kleihues P, Cavenee WK (Eds). IARC Press, Lyon, France (2000).
   Google Scholar
• Behin A, Hoang-Xuan K, Carpentier AF, Delattre JY. Primary brain tumors in adults. Lancet361, 323–331 (2003).
   PubMed Web of Science ®Google Scholar
• Wong ET, Hess KR, Gleason MJ et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto Phase II clinical trials. J. Clin. Oncol.17, 2572–2578 (1999).
   PubMed Web of Science ®Google Scholar
• Adjei AA, Hidalgo M. Intracellular signal transduction pathway proteins as targets for cancer therapy. J. Clin. Oncol.23, 5386–5403 (2005).
   PubMed Web of Science ®Google Scholar
• Dy GK, Adjei AA. Obstacles and opportunities in the clinical development of targeted therapeutics. Prog. Drug. Res.63, 19–41 (2005).
   PubMedGoogle Scholar
• Kesari S, Ramakrishna N, Sauvageot C, Stiles C, Wen PY. Targeted molecular therapies for recurrent malignant glioma. Curr. Oncol. Rep.8, 58–70 (2006).
   PubMedGoogle Scholar
• Mrugala M, Kesari S, Ramakrishna N, Wen PY. Therapy for recurrent malignant gliomas in adults. Expert Rev. Anticancer Ther.4, 759–782 (2004).
   PubMedGoogle Scholar
• Reardon DA, Wen PY. Therapeutic advances in the treatment of glioblastoma: rationale and potential role of targeted agents. Oncologist11, 152–164 (2006).
   PubMed Web of Science ®Google Scholar
• Raizer JJ. HER1/EGFR tyrosine kinase inhibitors for the treatment of glioblastoma multiforme. J. Neurooncol.74, 77–86 (2005).
   PubMed Web of Science ®Google Scholar
• Butowski N, Chang SM. Small molecule and monoclonal antibody therapies in neurooncology. Cancer Control12, 116–124 (2005).
   PubMedGoogle Scholar
• Reardon DA, Rich JN, Friedman HS, Bigner DD. Recent advances in the treatment of malignant astrocytoma. J. Clin. Oncol.24(8), 1253–1265 (2006).
   PubMed Web of Science ®Google Scholar
• Van Meir EG, Bellail A, Phuphanich S. Emerging molecular therapies for brain tumors. Semin. Oncol.31(2 Suppl. 4), 38–46 (2004).
   PubMedGoogle Scholar
• Arora A, Scholar EM. Role of tyrosine kinase inhibitors in cancer therapy. J. Pharmacol. Exp. Ther.315(3), 971–979 (2005).
   PubMed Web of Science ®Google Scholar
• Newton HB. Molecular neuro-oncology and the development of ‘targeted’ therapeutic strategies for brain tumors. Part 1 – growth factor and ras signaling pathways. Expert Rev. Anticancer Ther.3, 595–614 (2003).
   PubMedGoogle Scholar
• Newton HB. Molecular neuro-oncology and the development of ‘targeted’ therapeutic strategies for brain tumors. Part 2 – PI3K/Akt/PTEN, mTOR, SHH/PTCH, and angiogenesis. Expert Rev. Anticancer Ther.4, 105–128 (2004).
   PubMedGoogle Scholar
• Rich JN, Bigner DD. Development of novel targeted therapies in the treatment of malignant glioma. Nat. Rev. Drug Discov.3, 430–446 (2004).
   PubMed Web of Science ®Google Scholar
• Maher EA, Furnari FB, Bachoo RM et al. Malignant glioma: genetics and biology of a grave matter. Genes Dev.15(11), 1311–1333 (2001).
   PubMed Web of Science ®Google Scholar
• Kitange GJ, Templeton KL, Jenkins RB. Recent advances in the molecular genetics of primary gliomas. Curr. Opin. Oncol.15(3), 197–203 (2003).
   PubMed Web of Science ®Google Scholar
• Rao RD, James CD. Altered molecular pathways in gliomas: an overview of clinically relevant issues. Semin. Oncol.31(5), 595–604 (2004).
   PubMed Web of Science ®Google Scholar
• Sanson M, Thillet J, Hoang-Xuan K. Molecular changes in gliomas. Curr. Opin. Oncol.16, 607–613 (2004).
   PubMed Web of Science ®Google Scholar
• Ichimura K, Ohgaki H, Kleihues P, Collins VP. Molecular pathogenesis of astrocytic tumours. J. Neurooncol.70(2), 137–160 (2004).
   PubMed Web of Science ®Google Scholar
• Kleihues P, Ohgaki H. Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-oncol.1(1), 44–51 (1999).
   PubMedGoogle Scholar
• Tso CL, Freije WA, Day A et al. Distinct transcription profiles of primary and secondary glioblastoma subgroups. Cancer Res.66(1), 159–167 (2006).
   PubMed Web of Science ®Google Scholar
• van den Boom J, Wolter M, Kuick R et al. Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction. Am. J. Pathol.163, 1033–1043 (2003).
   PubMed Web of Science ®Google Scholar
• Mischel PS, Nelson SF, Cloughesy TF. Molecular analysis of glioblastoma: pathway profiling and its implications for patient therapy. Cancer Biol. Ther.2, 242–247 (2003).
   PubMed Web of Science ®Google Scholar
• Rao RD, Uhm JH, Krishnan S, James CD. Genetic and signaling pathway alterations in glioblastoma: relevance to novel targeted therapies. Front. Biosci.8, 270–280 (2003).
   Web of Science ®Google Scholar
• Shai R, Shi T, Kremen TJ, Horvath S et al. Gene expression profiling identifies molecular subtypes of gliomas. Oncogene22, 4918–4923 (2003).
   PubMed Web of Science ®Google Scholar
• Nutt CL, Mani DR, Betensky RA et al. Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res.63, 1602–1607 (2003).
   PubMed Web of Science ®Google Scholar
• Drucker BJ. Perspectives on the development of a molecularly targeted agent. Cancer Cell1, 31–36 (2002).
   PubMed Web of Science ®Google Scholar
• Rich J, Reardon DA, Peery TS et al. Phase II trial of ZD1839 for patients with first relapse glioblastoma. J. Clin. Oncol.22, 133–142 (2004).
   PubMed Web of Science ®Google Scholar
• Lieberman F, Cloughesy T, Deangelis LM et al. Phase I–II study of ZD-1839 for recurrent malignant gliomas and meningiomas progressing after radiation therapy. Proc. Am. Soc. Clin. Oncol. (2004) (Abstract 1510).
   Google Scholar
• Uhm JH, Ballman KV, Giannini JC et al. Phase II study of ZD1839/Iressa® in patients with newly diagnosed grade 4 astrocytoma. Proc. Am. Soc. Clin. Oncol. (2004) (Abstract 1505).
   Google Scholar
• Raizer JJ, Abrey L, Wen P et al. A Phase II trial of OSI-774 (Tarceva) in patients (pts) with recurrent malignant gliomas (MG) not on EIAEDs. Proc. Am. Soc. Clin. Oncol. (2004) (Abstract 1502).
   Google Scholar
• Prados M, Chang S, Burton E et al. Phase I study of erlotinib HCL alone and combined with temozolomide in patients with stable or recurrent malignant glioma. Neuro-oncology8, 67–78 (2006).
   PubMed Web of Science ®Google Scholar
• Vogelbaum MA, Peereboom D, Stevens G et al. Phase II trial of the EGFR tyrosine kinase inhibitor erlotinib for single agent therapy of recurrent glioblastoma multiforme: interim results. Proc. Am. Soc. Clin. Oncol. (2004) (Abstract 1558).
   Google Scholar
• Yung A, Vrendenburgh J, Cloughsey T et al. Erlotinib HCL for glioblastoma multiforme in first relapse, a Phase II trial. Proc. Am. Soc. Clin. Oncol. (2004) (Abstract 1555).
   PubMedGoogle Scholar
• Cloughesy T, Yung A, Vrendenberg J et al. Phase II study of erlotinib in recurrent GBM: molecular predictors of outcome. Proc. Am. Soc. Clin. Oncol. (2005) (Abstract 1507).
   PubMedGoogle Scholar
• Mellinghoff IK, Wang MY, Vivanco I et al. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N. Engl. J. Med.353(19), 2012–2024 (2005).
   PubMed Web of Science ®Google Scholar
• Haas-Kogan DA, Prados MD, Tihan T et al. Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib. J. Natl Cancer Inst.97(12), 880–887 (2005).
   PubMed Web of Science ®Google Scholar
• Haas-Kogan DA, Prados MD, Lamborn KR, Tihan T, Berger MS, Stokoe D. Biomarkers to predict response to epidermal growth factor receptor inhibitors. Cell Cycle4(10), 1369–1372 (2005).
   PubMed Web of Science ®Google Scholar
• Lassman AB, Rossi MR, Razier JR et al. Molecular study of malignant gliomas treated with the EGFR inhibitor erlotinib (OSI-774): tissue analysis from a North American Brain Tumor Consortium (NABTC) study. Clin. Cancer Res.11, 7841–7850 (2005).
   PubMed Web of Science ®Google Scholar
• Barber TD, Vogelstein B, Kinzler KW, Velculescu VE. Somatic mutations of EGFR in colorectal cancers and glioblastomas. N. Engl. J. Med.351(27), 2883 (2004).
   PubMed Web of Science ®Google Scholar
• Guha A, Dashner K, Black PM et al.In vivo expression of PDGF and PDGF receptors in human astrocytomas. Int. J. Cancer60, 168–173 (1995).
   PubMed Web of Science ®Google Scholar
• Kilic T, Alberta J, Zdunek PR et al. Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res.60, 5143–5150 (2000).
   PubMed Web of Science ®Google Scholar
• Wen PY, Yung WKA, Lamborn KR et al. Phase I/II study of imatinib mesylate (Gleevec) for recurrent malignant gliomas North American Brain Tumor Consortium Study 99–08. Society for neuro-oncology 9th annual meeting. Toronto, Canada, 18–21 November 2004 (Abstract TA-63).
   Google Scholar
• Raymond E, Brandes A, Van Oosterom A et al. Multicentre Phase II study of imatinib mesylate in patients with recurrent glioblastoma: an EORTC: NDDG/BTG Intergroup Study. Proceedings of the American Society of Clinical Oncology. New Orleans, LA, USA, 5–8 June 2004 (Abstract 1501).
   Google Scholar
• van den Bent M, Brandes AA, Van Oosterom A et al. Multicentre Phase II study of imatinib mesylate in patients with recurrent anaplastic oligodendroglioma (AOD)/mixed oligoastrocytoma (MOA) and anaplastic astrocytoma (AA)/low grade astrocytoma (LGA): an EORTC New Drug Development Group (NDDG) and Brain Tumor Group (BTG) study. Proceedings of the American Society of Clinical Oncology. Orlando, FL, USA, 13–17 May 2005 (Abstract 1517).
   Google Scholar
• Adjei AA. Farnesyltransferase inhibitors. Cancer Chemother. Biol. Response Modif.22, 123–133 (2005).
   PubMedGoogle Scholar
• Cloughesy TF, Kuhn J, Robins HI et al. A Phase I trial of R115777 in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs (EIAEDs): a North American Brain Tumor Consortium Study. J. Clin. Oncol.23, 6647–6656 (2005).
   PubMed Web of Science ®Google Scholar
• Cloughesy TFKuhn J, Wen PY, et al. Two Phase II trials of R115777 (Zarnestra) in patients with recurrrent glioblastoma multiforme: a comparison of patients on enzyme-inducing anti-epileptic drugs (EIAED)and not on eiaed at maximum tolerated dose respectively: a North American Brain Tumor Consortium (NABTC) report. Society For Neuro-Oncology 8th Annual Meeting.Neuro-Oncology5, 349(2003) (Abstract TA-10).
   Google Scholar
• Mita MM, Mita A, Rowinsky EK. The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Cancer Biol. Ther.2(4 Suppl. 1), S169–S177 (2003).
   PubMed Web of Science ®Google Scholar
• Chang S, Kuhn J, Wen P et al. Phase I/Pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme inducing antiepileptic drugs. Invest. New Drugs22, 427–435 (2004).
   PubMed Web of Science ®Google Scholar
• Chang SM, Wen P, Cloughesy T et al. Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme. Invest. New Drugs23, 357–361 (2005).
   PubMed Web of Science ®Google Scholar
• Galanis E, Buckner JC, Maurer MJ et al. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J. Clin. Oncol.23(23), 5294–5304 (2005).
   PubMed Web of Science ®Google Scholar
• Conrad C, Friedman H, Reardon D et al. A Phase I/II trial of single-agent PTK787/ZK222584, a novel oral angiogenesis inhibitor, in patients with recurrent GBM. Proceedings of the American Society of Clinical Oncology New Orleans, LA, USA, 5–8 June 2004 (Abstract 1512).
   Google Scholar
• Reardon D, Friedman H, Brada M et al. A Phase I/II trial of PTK787/ZK 222584 (PTK/ZK), a multi-VEGF receptor tyrosine kinase inhibitor, in combination with either temozolomide or lomustine for patients with recurrent glioblastoma multiforme (GBM). Society for neuro-oncology 9th annual meeting. Toronto, Canada, 18–21 November 2004 (Abstract TA–48).
   Google Scholar
• Stark-Vance V. Bevacizumab and CPT-11 in the treatement of relapsed malignant lioma. Proceedings of the World Federation of Neuro-oncology 2nd Quadrennial Meeting. Edinburgh, UK, 5–8 May 2005 (Abstract 342).
   Google Scholar
• Holash J, Davis S, Papadopoulos N et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc. Natl Acad. Sci. USA99(17), 11393–11398 (2002).
   PubMed Web of Science ®Google Scholar
• Graff JR, McNulty AM, Hanna KR et al. The protein kinase C β-selective inhibitor, enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts. Cancer Res.65(16), 7462–7469 (2005).
   PubMed Web of Science ®Google Scholar
• Fine HA, Kim L, Royce C et al. A Phase II trial of LY317615 in patients with recurrent high grade gliomas. Proc. Am. Soc. Clin. Oncol. (2004) (Abstract 1504).
   Google Scholar
• Joki T, Heese O, Nikas DC et al. Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398. Cancer Res.60, 4926–4931 (2000).
   PubMed Web of Science ®Google Scholar
• Shono T, Tofilon PJ, Bruner JM, Owolabi O, Lang FF. Cyclooxygenase-2 expression in human gliomas: prognostic significance and molecular correlations. Cancer Res.61, 4375–4381 (2001).
   PubMed Web of Science ®Google Scholar
• Lefranc F, Brotchi J, Kiss R. Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis. J. Clin. Oncol.23, 2411–2422 (2005).
   PubMed Web of Science ®Google Scholar
• Groves MD, Puduvalli VK, Hess KR et al. Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme. J. Clin. Oncol.20(5), 1383–1388 (2002).
   PubMed Web of Science ®Google Scholar
• MacDonald TJ, Taga T, Shimada H et al. Preferential susceptibility of brain tumors to the antiangiogenic effects of an α(v) integrin antagonist. Neurosurgery48, 151–157 (2001).
   PubMed Web of Science ®Google Scholar
• Nabors LB, Rosenfeld SS, Mikkelsen T et al. NABTT9911: a Phase I trial of EMD 121974 for treatment of patients with recurrent malignant gliomas. Society for neuro-oncology 9th annual meeting. Toronto, Canada, 18–21 November 2004 (Abstract TA-39).
   Google Scholar
• Marks PA, Richon VM, Miller T, Kelly WK. Histone deacetylase inhibitors. Adv. Cancer Res.91, 137–168 (2004).
   PubMed Web of Science ®Google Scholar
• Marks PA, Rifkind RA, Richon VM et al. Histone deacetylases and cancer: causes and therapies. Nat. Cancer Rev.1, 194–202 (2001).
   PubMed Web of Science ®Google Scholar
• Adams J. The proteasome: a suitable antineoplastic target. Nat. Rev. Cancer4(5), 349–360 (2004).
   PubMed Web of Science ®Google Scholar
• Yin D, Zhou H, Kumagai T et al. Proteasome inhibitor PS-341 causes cell growth arrest and apoptosis in human glioblastoma multiforme (GBM). Oncogene24(3), 344–354 (2005).
   PubMed Web of Science ®Google Scholar
• Nakanishi C, Toi M. Nuclear factor-κB inhibitors as sensitizers to anticancer drugs. Nat. Rev. Cancer.5(4), 297–309 (2005).
   PubMed Web of Science ®Google Scholar
• Mischel PS, Cloughesy TF, Nelson SF. DNA-microarray analysis of brain cancer: molecular classification for therapy. Nat. Rev. Neurosci.5(10), 782–792 (2004).
   PubMed Web of Science ®Google Scholar
• Rual JF, Venkatesan K, Hao T et al. Towards a proteome-scale map of the human protein–protein interaction network. Nature437(7062), 1173–1178 (2005).
   PubMed Web of Science ®Google Scholar
• Barabasi AL, Oltvai ZN. Network biology: understanding the cell's functional organization. Nat. Rev. Genet.5, 101–113 (2004).
   PubMed Web of Science ®Google Scholar
• Bredel M, Bredel C, Juric D et al. Tumor necrosis factor-α-induced protein 3 as a putative regulator of nuclear factor-α B-mediated resistance to 06-alkylating agents in human glioblastomas. J. Clin. Oncol.24, 274–287 (2006).
   PubMed Web of Science ®Google Scholar
• Bredel M, Bredel C, Juric D et al. Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas. Cancer Res.65(19), 8679–8689 (2005).
   PubMedGoogle Scholar
• Robe PA, Bentires-Alj M, Bonif M et al.In vitro and in vivo activity of the nuclear factor-κ B inhibitor sulfasalazine in human glioblastomas. Clin. Cancer Res.10(16), 5595–5603 (2004).
   PubMed Web of Science ®Google Scholar
• Steinbach JP, Eisenmann C, Klumpp A, Weller M. Co-inhibition of epidermal growth factor receptor and type 1 insulin-like growth factor receptor synergistically sensitizes human malignant glioma cells to CD95L-induced apoptosis. Biochem. Biophys. Res. Commun.321(3), 524–530 (2004).
   PubMed Web of Science ®Google Scholar
• Lu D, Zhang H, Ludwig D et al. Simultaneous blockade of both the epidermal growth factor receptor and the insulin-like growth factor receptor signaling pathways in cancer cells with a fully human recombinant bispecific antibody. J. Biol. Chem.279(4), 2856–2865 (2004).
   PubMed Web of Science ®Google Scholar
• Abounader R, Laterra J. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro-oncology7(4), 436–451 (2005).
   PubMed Web of Science ®Google Scholar
• Lamszus K, Heese O, Westphal M. Angiogenesis-related growth factors in brain tumors. Cancer Treat. Res.117, 169–190 (2004).
   PubMedGoogle Scholar
• Hjelmeland MD, Hjelmeland AB, Sathornsumetee S et al. SB-431542, a small molecule transforming growth factor-β-receptor antagonist, inhibits human glioma cell line proliferation and motility. Mol. Cancer Ther.3(6), 737–745 (2004).
   PubMed Web of Science ®Google Scholar
• Uhl M, Aulwurm S, Wischhusen J et al. SD-208, a novel transforming growth factor β receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo.Cancer Res.64(21), 7954–7961 (2004).
   PubMed Web of Science ®Google Scholar
• Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat. Cancer Rev.4, 937–947 (2004).
   PubMed Web of Science ®Google Scholar
• Premkumar DR, Arnold B, Jane EP, Pollack IF. Synergistic interaction between 17-AAG and phosphatidylinositol 3-kinase inhibition in human malignant glioma cells. Mol. Carcinog.45(1), 47–59 (2006).
   PubMed Web of Science ®Google Scholar
• Nakada M, Niska JA, Miyamori H et al. The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells. Cancer Res.64(9), 3179–3185 (2004).
   PubMedGoogle Scholar
• Edwards LA, Thiessen B, Dragowska WH, Daynard T, Bally MB, Dedhar S. Inhibition of ILK in PTEN-mutant human glioblastomas inhibits PKB/Akt activation, induces apoptosis, and delays tumor growth. Oncogene24(22), 3596–3605 (2005).
   PubMedGoogle Scholar
• Koul D, Shen R, Bergh S et al. Targeting integrin-linked kinase inhibits Akt signaling pathways and decreases tumor progression of human glioblastoma. Mol. Cancer Ther.4(11), 1681–1688 (2005).
   PubMed Web of Science ®Google Scholar
• Angers-Loustau A, Hering R, Werbowetski TE, Kaplan DR, Del Maestro RF. SRC regulates actin dynamics and invasion of malignant glial cells in three dimensions. Mol. Cancer Res.2(11), 595–605 (2004).
   PubMed Web of Science ®Google Scholar
• Stettner MR, Wang W, Nabors LB et al. Lyn kinase activity is the predominant cellular SRC kinase activity in glioblastoma tumor cells. Cancer Res.65(13), 5535–5543 (2005).
   PubMed Web of Science ®Google Scholar
• Natarajan M, Stewart JE, Golemis EA et al. HEF1 is a necessary and specific downstream effector of FAK that promotes the migration of glioblastoma cells. Oncogene25, 1721–1732 (2005).
   Google Scholar
• Pulford K, Lamant L, Espinos E et al. The emerging normal and disease-related roles of anaplastic lymphoma kinase. Cell. Mol. Life Sci.61(23), 2939–2953 (2004).
   PubMed Web of Science ®Google Scholar
• Kaur B, Khwaja FW, Severson EA et al. Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro-oncology7(2), 134–153 (2005).
   PubMed Web of Science ®Google Scholar
• Swanton C. Cell-cycle targeted therapies. Lancet Oncol.5(1), 27–36 (2004).
   PubMed Web of Science ®Google Scholar
• Newcomb EW, Tamasdan C, Entzminger Y et al. Flavopiridol inhibits the growth of GL261 gliomas in vivo: implications for malignant glioma therapy. Cell Cycle3(2), 230–234 (2004).
   PubMed Web of Science ®Google Scholar
• Kondo Y, Hollingsworth EF, Kondo S. Molecular targeting for malignant gliomas. Int. J. Oncol.24(5), 1101–1109 (2004).
   PubMed Web of Science ®Google Scholar
• Luo Y, Leverson JD. New opportunities in chemosensitization and radiosensitization: modulating the DNA-damage response. Expert Rev. Anticancer Ther.5(2), 333–342 (2005).
   PubMed Web of Science ®Google Scholar
• Oltersdorf T, Elmore SW, Shoemaker AR et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature435(7042), 677–681 (2005).
   PubMed Web of Science ®Google Scholar
• Liston P, Fong WG, Korneluk RG. The inhibitors of apoptosis: there is more to life than Bcl2. Oncogene22(53), 8568–8580 (2003).
   PubMed Web of Science ®Google Scholar
• Schimmer AD, Dalili S. Targeting the IAP family of caspase inhibitors as an emerging therapeutic strategy. Hematology (Am. Soc. Hematol. Educ. Program) 215–219 (2005).
   PubMedGoogle Scholar
• Schimmer AD, Dalili S, Batey RA, Riedl SJ. Targeting XIAP for the treatment of malignancy. Cell Death Differ.13(2), 179–188 (2006).
   PubMed Web of Science ®Google Scholar
• Ghobrial IM, Witzig TE, Adjei AA. Targeting apoptosis pathways in cancer therapy. CA Cancer J. Clin.55(3), 178–194 (2005).
   PubMed Web of Science ®Google Scholar
• Rubin JB, Kung AL, Klein RS et al. A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc. Natl Acad. Sci. USA100, 13513–13518 (2003)
   PubMedGoogle Scholar
• Guzman M. Cannabinoids: potential anticancer agents. Nat. Rev. Cancer3, 745–755 (2003)
   PubMedGoogle Scholar
• Sanchez C, de Ceballos ML, del Pulgar TG et al. Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. Cancer Res.61, 5784–5789 (2001)
   PubMedGoogle Scholar
• Senderowicz AM. Targeting cell cycle and apoptosis for the treatment of human malignancies. Curr. Opin. Cell Biol.16(6), 670–678 (2004).
   PubMed Web of Science ®Google Scholar
• Senderowicz AM. Inhibitors of cyclin-dependent kinase modulators for cancer therapy. Prog. Drug Res.63, 183–206 (2005).
   PubMedGoogle Scholar
• Schwartz GK, Shah MA. Targeting the cell cycle: a new approach to cancer therapy. J. Clin. Oncol.23(36), 9408–9421 (2005).
   PubMed Web of Science ®Google Scholar
• Newton HB. Molecular neuro-oncology and the development of targeted therapeutic strategies for brain tumors. Part 5: apoptosis and cell cycle. Expert Rev. Anticancer Ther.5(2), 355–378 (2005).
   PubMed Web of Science ®Google Scholar
• Reed JC. Apoptosis-targeted therapies for cancer. Cancer Cell3, 17–22 (2003).
   PubMed Web of Science ®Google Scholar
• Rowinsky EK. Targeted induction of apoptosis in cancer management: the emerging role of tumor necrosis factor-related apoptosis-inducing ligand receptor activating agents. J. Clin. Oncol.23, 9394–9407 (2005).
   PubMed Web of Science ®Google Scholar
• Piro LD. Apoptosis, Bcl-2 antisense, and cancer therapy. Oncology18(13 Suppl. 10), 5–10 (2004).
   PubMedGoogle Scholar
• Letai A, Bassik MC, Walensky LD et al. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell.2(3), 183–192 (2002).
   PubMed Web of Science ®Google Scholar
• Ehtesham M, Winston JA, Kabos P, Thompson RC. CXCR4 expression mediates glioma cell invasiveness. Oncogene (2006) [Epub ahead of print].
   PubMedGoogle Scholar
• Yang SX, Chen JH, Jiang XF et al. Activation of chemokine receptor CXCR4 in malignant glioma cells promotes the production of vascular endothelial growth factor. Biochem. Biophys. Res. Commun.335(2), 523–528 (2005).
   PubMedGoogle Scholar
• McAllister SD, Chan C, Taft RJ et al. Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. J. Neurooncol.74(1), 31–40 (2005).
   PubMedGoogle Scholar
• Hu X, Holland EC. Application of mouse gliomas models in preclinical trials. Mut. Res.576, 54–65 (2005).
   PubMed Web of Science ®Google Scholar
• Giannini C, Sarkaria JN, Saito A et al. Patient tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme. Neuro-oncology7(2), 164–176 (2005).
   PubMed Web of Science ®Google Scholar
• Frantz S. Playing dirty. Nature437, 942–943 (2005).
   PubMed Web of Science ®Google Scholar
• Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat. Rev. Cancer.5(10), 761–772 (2005).
   PubMed Web of Science ®Google Scholar
• Yang J, Yang JM, Iannone M. Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin. Cancer Res.61(10), 4010–4016 (2001).
   PubMed Web of Science ®Google Scholar
• Camphausen K, Tofilon PJ. Combining radiation and molecular targeting in cancer therapy. Cancer Biol. Ther.3, 247–250 (2004).
   PubMed Web of Science ®Google Scholar
• Reardon DA, Quinn JA, Vredenburgh JJ et al. Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma. Clin. Cancer Res.12(3 Pt 1), 860–868 (2006).
   PubMed Web of Science ®Google Scholar
• Doherty L, Gigas D, Kesari S et al. Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas. Neurology (2006) (In press).
   Google Scholar
• Camirand A, Zakikhani M, Young F, Pollak M. Inhibition of insulin-like growth factor-1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer cells. Breast Cancer Res.7(4), R570–R579 (2005).
   PubMed Web of Science ®Google Scholar
• Premkumar DR, Arnold B, Jane EP, Pollack IF. Synergistic interaction between 17-AAG and phosphatidylinositol 3-kinase inhibition in human malignant glioma cells. Mol. Carcinog.45(1), 47–59 (2006).
   PubMed Web of Science ®Google Scholar
• Hui AM, Zhang W, Chen W et al. Agents with selective estrogen receptor (ER) modulator activity induce apoptosis in vitro and in vivo in ER-negative glioma cells. Cancer Res.64(24), 9115–9123 (2004).
   PubMed Web of Science ®Google Scholar
• Zhang M, Chakravarti A. Novel radiation-enhancing agents in malignant gliomas. Semin. Radiat. Oncol.16(1), 29–37 (2006).
   PubMed Web of Science ®Google Scholar
• Chinnaiyan P, Allen GW, Harari PM. Radiation and new molecular agents, part II: targeting HDAC, HSP90, IGF-1R, PI3K, and Ras. Semin. Radiat. Oncol.16(1), 59–64 (2006).
   PubMed Web of Science ®Google Scholar
• Stupp R, Mason WP, van den Bent MJ et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med.352(10), 987–996 (2005).
   PubMed Web of Science ®Google Scholar
• Chakravarti A, Dicker A, 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(3), 927–931 (2004).
   PubMed Web of Science ®Google Scholar
• Kim DW, Huamani J, Fu A et al. Molecular strategies targeting the host component of cancer to enhance tumor response to radiationtherapy. Int. J. Radiat. Oncol. Biol. Phys.64, 38–46 (2006).
   PubMed Web of Science ®Google Scholar
• Horsman MR, Bohm L, Margison GP et al. Tumor radiosensitizers-current status of development of various approaches: report of an International Atomic Energy Agency meeting. Int. J. Radiat. Oncol. Biol. Phys.64(2), 551–561 (2006).
   PubMed Web of Science ®Google Scholar
• Sartor CI. Mechanisms of disease: radiosensitization by epidermal growth factor receptor inhibitors. Nat. Clin. Pract. Oncol.1, 80–87 (2004).
   PubMedGoogle Scholar
• Chakravarti A, Loeffler JS, Dyson NJ. Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res.62(1), 200–207 (2002).
   PubMed Web of Science ®Google Scholar
• Holdhoff M, Kreuzer KA, Appelt C. Imatinib mesylate radiosensitizes human glioblastoma cells through inhibition of platelet-derived growth factor receptor. Blood Cells Mol. Dis.34(2), 181–185 (2005).
   PubMedGoogle Scholar
• Russell JS, Brady K, Burgan WE et al. Gleevec-mediated inhibition of Rad51 expression and enhancement of tumor cell radiosensitivity. Cancer Res.63(21), 7377–7383 (2003).
   PubMed Web of Science ®Google Scholar
• Geng L, Shinohara ET, Kim D et al. STI571 (Gleevec) improves tumor growth delay and survival in irradiated mouse models of glioblastoma. Int. J. Radiat. Oncol. Biol. Phys.64, 263–271 (2006).
   PubMed Web of Science ®Google Scholar
• Delmas C, Heliez C, Cohen-Jonathan E et al. Farnesyltransferase inhibitor, R115777, reverses the resistance of human glioma cell lines to ionizing radiation. Int. J. Cancer100(1), 43–48 (2002).
   PubMed Web of Science ®Google Scholar
• Shinohara ET, Cao C, Niermann K et al. Enhanced radiation damage of tumor vasculature by mTOR inhibitors. Oncogene24(35), 5414–5422 (2005).
   PubMed Web of Science ®Google Scholar
• Eshleman JS, Carlson BL, Mladek AC, Kastner BD, Shide KL, Sarkaria JN. Inhibition of the mammalian target of rapamycin sensitizes U87 xenografts to fractionated radiation therapy. Cancer Res.62(24), 7291–7297 (2002).
   PubMed Web of Science ®Google Scholar
• Russell JS, Burgan W, Oswald KA, Camphausen K, Tofilon PJ. Enhanced cell killing induced by the combination of radiation and the heat shock protein 90 inhibitor 17-allylamino-17- demethoxygeldanamycin: a multitarget approach to radiosensitization. Clin. Cancer Res.9(10 Pt 1), 3749–3755 (2003).
   PubMed Web of Science ®Google Scholar
• Citrin D, Menard C, Camphausen K. Combining radiotherapy and angiogenesis inhibitors: clinical trial design. Int. J. Radiat. Oncol. Biol. Phys.64(1), 15–25 (2006).
   PubMed Web of Science ®Google Scholar
• Geng L, Donnelly E, McMahon G et al. Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy. Cancer Res.61(6), 2413–2419 (2001).
   PubMed Web of Science ®Google Scholar
• Winkler F, Kozin SV, Tong RT et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell6(6), 553–563 (2004).
   PubMed Web of Science ®Google Scholar
• Damiano V, Melisi D, Bianco C et al. Cooperative antitumor effect of multitargeted kinase inhibitor ZD6474 and ionizing radiation in glioblastoma. Clin. Cancer Res.11(15), 5639–5644 (2005).
   PubMed Web of Science ®Google Scholar
• Frederick B, Gustafson D, Bianco C et al. ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinase activity in combination with radiotherapy. Int. J. Radiat. Oncol. Biol. Phys.64(1), 33–37 (2006).
   PubMed Web of Science ®Google Scholar
• Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med.350(23), 2335–2342 (2004).
   PubMed Web of Science ®Google Scholar
• Herbst RS, Prager D, Hermann R et al. TRIBUTE: a Phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J. Clin. Oncol.23(25), 5892–5899 (2005).
   PubMed Web of Science ®Google Scholar
• Gilbert MR, Hess K, Gaupp P et al. A Phase I study of temozolomide (TMZ) and the farnesyltransferase inhibitor (FTI), tipifarnib (ZARNESTRA, R115777) in recurrent glioblastoma: a dose and schedule intensive regimen. Society for neuro-oncology9th annual meeting. Toronto, Canada, 18–21 November 2004 (Abstract TA-23).
   Google Scholar
• Dresemann G. Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: a patient series. Ann. Oncol.16(10), 1702–1708 (2005).
   PubMed Web of Science ®Google Scholar
• Reardon DA, Egorin MJ, Quinn J et al. Phase II study of imatinib mesylate plus hydroxyurea is adults with recurrent glioblastoma multiforme. J. Clin. Oncol.23, 9359–9368 (2005).
   PubMed Web of Science ®Google Scholar
• Quinn JA, Desjardins A, Weingart J et al. Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J. Clin. Oncol.23(28), 7178–7187 (2005).
   PubMed Web of Science ®Google Scholar
• Barvaux VA, Ranson M, Brown R et al. Dual repair modulation reverses Temozolomide resistance in vitro.Mol. Cancer Ther.3(2), 123–127 (2004).
   PubMed Web of Science ®Google Scholar
• Woolford LB, Southgate TD, Margison GP et al. The P140K mutant of human O(6)-methylguanine-DNA-methyltransferase (MGMT) confers resistance in vitro and in vivo to temozolomide in combination with the novel MGMT inactivator O(6)-(4-bromothenyl)guanine. J. Gene Med.8(1), 29–34 (2006).
   PubMed Web of Science ®Google Scholar
• Plummer R, Middleton M, Wilson R et al. Final clinical, pharmacokinetic and pharmacodynamic results of the Phase I study of the novel poly(ADP-ribose)polymerase (PARP) inhibitor, AGO14699, in combination with temozolomide. AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. CA, USA, 14–18 November 2005 (Abstract B268).
   Google Scholar
• Tentori L, Graziani G. Chemopotentiation by PARP inhibitors in cancer therapy. Pharmacol. Res.52(1), 25–33 (2005).
   PubMed Web of Science ®Google Scholar
• Tentori L, Leonetti C, Scarsella M et al. Brain distribution and efficacy as chemosensitizer of an oral formulation of PARP-1 inhibitor GPI 15427 in experimental models of CNS tumors. Int. J. Oncol.26(2), 415–422 (2005).
   PubMedGoogle Scholar
• Weaver KD, Yeyeodu S, Cusack JC Jr, Baldwin AS Jr, Ewend MG. Potentiation of chemotherapeutic agents following antagonism of nuclear factor κ B in human gliomas. J. Neurooncol.61(3), 187–196 (2003).
   PubMed Web of Science ®Google Scholar
• Papadopoulos MC, Saadoun S, Binder DK et al. Molecular mechanisms of brain tumor edema. Neuroscience129, 1011–1020 (2004).
   PubMed Web of Science ®Google Scholar
• Breedveld P, Beijnen JH, Schellens JH. Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugs. Trends Pharmacol. Sci.27(1), 17–24 (2006).
   PubMed Web of Science ®Google Scholar
• Loscher W, Potschka H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat. Cancer Rev.6, 591–602 (2005).
   Google Scholar
• Peng B, Lloyd P, Schran H. Clinical pharmacokinetics of imatinib. Clin. Pharmacokinet.44(9), 879–894 (2005).
   PubMed Web of Science ®Google Scholar
• Kemper EM, Boogerd W, Thuis I, Beijnen JH, van Tellingen O. Modulation of the blood–brain barrier in oncology: therapeutic opportunities for the treatment of brain tumours? Cancer Treat Rev.30(5), 415–423 (2004).
   PubMed Web of Science ®Google Scholar
• Bauer B, Hartz AM, Fricker G, Miller DS. Modulation of p-glycoprotein transport function at the blood–brain barrier. Exp. Biol. Med.230(2), 118–27 (2005).
   PubMed Web of Science ®Google Scholar
• Fricker G, Miller DS. Modulation of drug transporters at the blood–brain-barrier. Pharmacology70, 169–176 (2004)
   PubMed Web of Science ®Google Scholar
• Westphal M, Hilt DC, Bortey E et al. A Phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel® wafers) in patients with primary malignant glioma. Neuro-oncology5, 79–88 (2003).
   PubMed Web of Science ®Google Scholar
• Husain SR, Puri RK. Interleukin-13 receptor-directed cytotoxin for malignant glioma therapy: from bench to bedside. J. Neurooncol.65, 37–48 (2003).
   PubMed Web of Science ®Google Scholar
• Kunwar S, Prados M, Chang S et al. Peritumoral convection-enhanced delivery of IL-13-PE38QQR in patients with recurrent malignant glioma-Phase I interim results. Neuro-oncol.5, 350 (2003) (Abstract TA-15).
   Google Scholar
• Prados M, Kunwar S, Lang FF et al. Final results of Phase I/II studies of IL13-PE38QQR administered intratumorally (IT) and/or peritumorally (PT) via convection-enhanced delivery (CED) in patients undergoing tumor resection for recurrent malignant gliomas. Proc. Am. Soc. Clin. Oncol. (2005) (Abstract 1504).
   Google Scholar
• Kawakami M, Kawakami K, Puri RK. Interleukin-4-Pseudomonas exotoxin chimeric fusion protein for malignant glioma therapy. J. Neurooncol.65(1), 15–25 (2003).
   PubMed Web of Science ®Google Scholar
• Weber F, Asher A, Bucholz R et al. Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma. J. Neurooncol.64, 125–137 (2003).
   PubMed Web of Science ®Google Scholar
• Rainov NG, Soling A. Technology evaluation: TransMID, KS Biomedix/ Nycomed/Sosei/PharmaEngine. Curr. Opin. Mol. Ther.7(5), 483–492 (2005).
   PubMedGoogle Scholar
• Sampson JH, Akabanai G, Archer GE et al. Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-α and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors. J. Neurooncol.65, 27–35 (2003).
   PubMed Web of Science ®Google Scholar
• Mamelak AN, Raubitschek A, Morgan R et al. A Phase I/II trail of intracavitary 131I-TM-601 in adult patients with recurrent high-grade-glioma. Society of Neuro-oncology 8th Annual Meeting. CO, USA, 13–16 November 2003 (Abstract RA-19).
   Google Scholar
• Lang FF, Gilbert MR, Puduvalli VK et al. Toward better early-Phase brain tumor clinical trials: a reappraisal of current methods and proposals for future strategies. Neuro-oncology4, 268–277 (2004).
   Google Scholar
• Puduvalli VK, Lang F, Levin L et al. Targeted therapies against malignant gliomas: approaches to trial design and correlative studies. Front. Biosci. (2006) (In press).
   Google Scholar
• Olson JJ, Supko J, Phuphanich S et al. Intratumoral pharmacokinetics determined with microdialysis in a patient with glioblastoma multiforme following administration of high dose methotrexate. Proceedings of the American Society of Clinical Oncology. Orlando, FL, USA, 13–17 May 2005 (Abstract1569).
   Google Scholar
• Kelloff GJ, Krohn KA, Larson SM et al. The progress and promise of molecular imaging probes in oncologic drug development. Clin. Cancer Res.11(22), 7967–7985 (2005).
   PubMed Web of Science ®Google Scholar
• Shah K, Weissleder R. Molecular optical imaging: applications leading to the development of present day therapeutics. NeuroRx2, 215–225 (2005).
   PubMedGoogle Scholar
• Jacobs AH, Kracht LW, Grossman A et al. Imaging in neuro-oncology NeuroRx2, 333–345 (2005).
   PubMedGoogle Scholar
• Chen W, Cloughesy T, Kamdar N et al. Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG. J. Nucl. Med.46(6), 945–952 (2005).
   PubMed Web of Science ®Google Scholar
• Lynch TJ, Bell DW, Sordella R et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med.350, 2129–2139 (2004).
   PubMed Web of Science ®Google Scholar
• Reardon DA, Wen P, Lyons P et al. A Phase I trial of AP23573, a novel mTOR inhibitor, in patients with recurrent malignant glioma. AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. CA, USA, 14–18 November 2005 (Abstract A195).
   Google Scholar
• Prados MD, Yung WK, Jaeckle KA et al. Phase 1 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study. Neuro-oncology6(1), 44–54 (2004).
   PubMed Web of Science ®Google Scholar
• Wen PY, Marks PW. Medical management of patients with brain tumors. Curr. Opin. Oncol.14, 299–307 (2002).
   PubMedGoogle Scholar
• Van den Abbeele AD, Badawi RD. Use of positron emission tomography in oncology and its potential role to assess response to imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs). Eur. J. Cancer38(Suppl. 5), S60–S65 (2002).
   PubMed Web of Science ®Google Scholar
• Hamstra DA, Chenevert TL, Moffat BA et al. Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma. Proc. Natl Acad. Sci. USA102(46), 16759–16764 (2005).
   PubMedGoogle Scholar
• Covarrubias DJ, Rosen BR, Lev MH. Dynamic magnetic resonance perfusion imaging of brain tumors. Oncologist9(5), 528–537 (2004).
   PubMed Web of Science ®Google Scholar
• Rehman S, Jayson GC. Molecular imaging of antiangiogenic agents. Oncologist10(2), 92–103 (2005).
   PubMed Web of Science ®Google Scholar
• Warmuth C, Gunther M, Zimmer C. Quantification of blood flow in brain tumors: comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging. Radiology228(2), 523–532 (2003).
   PubMed Web of Science ®Google Scholar
• Beaudry P, Force J, Naumov GN et al. Differential effects of vascular endothelial growth factor receptor-2 inhibitor ZD6474 on circulating endothelial progenitors and mature circulating endothelial cells: implications for use as a surrogate marker of antiangiogenic activity. Clin. Cancer Res.11(9), 3514–3522 (2005).
   PubMed Web of Science ®Google Scholar
• Pelloski CE, Mahajan A, Maor M et al. YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma. Clin. Cancer Res.11(9), 3326–3334 (2005).
   PubMed Web of Science ®Google Scholar
• Reardon DA, Wen PY. Therapeutic advances in the treatment of glioblastoma: rationale and potential role of targeted agents. Oncologist11, 152–164 (2006).
   Google Scholar