Molecularly targeted therapies for malignant gliomas: advances and challenges

References

• American Cancer Society. Cancer Facts and Figures 2005. American Cancer Society, Atlanta, GA, USA (2005).
   Google Scholar
• CBTRUS. Statistical Report: Primary Brain Tumors in the United States, 1998–2002. Central Brain Tumor Registry of the United States, Hinsdale, IL, USA (2005).
   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, 987–996 (2005).
   PubMed Web of Science ®Google Scholar
• Butowski NA, Sneed PK, Chang SM. Diagnosis and treatment of recurrent high-grade astrocytoma. J. Clin. Oncol.24, 1273–1280 (2006).
   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
• 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
• Costa J. Pathology confronts molecular targeted therapies. Nat. Clin. Pract. Oncol.3(3), 113 (2006).
   PubMedGoogle Scholar
• Ichimura K, Ohgaki H, Kleihues P, Collins VP. Molecular pathogenesis of astrocytic tumours. J. Neurooncol.70, 137–160 (2004).
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. The hallmarks of cancer. Cell100, 57–70 (2000).
   PubMed Web of Science ®Google Scholar
• Newton HB. Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 1: growth factor and Ras signaling pathways. Expert Rev. Anticancer Ther.3(5), 595–614 (2003).
   PubMedGoogle Scholar
• Newton HB. Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 2: PI3K/Akt/PTEN, mTOR, SHH/PTCH and angiogenesis. Expert Rev. Anticancer Ther.4(1), 105–128 (2004).
   PubMedGoogle Scholar
• Newton HB. Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 3: brain tumor invasiveness. Expert Rev. Anticancer Ther.4(5), 803–821 (2004).
   PubMedGoogle Scholar
• Newton HB. Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 4: p53 signaling pathway. Expert Rev. Anticancer Ther.5(1), 177–191 (2005).
   PubMed Web of Science ®Google Scholar
• Newton HB. Molecular neuro-oncology and 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
• 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, 927–931 (2004).
   PubMed Web of Science ®Google Scholar
• Morabito A, De Maio E, Di Maio M, Normanno N, Perronea F. Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions. Oncologist11, 753–764 (2006).
   PubMed Web of Science ®Google Scholar
• Singh SK, Hawkins C, Clarke ID et al. Identification of human brain tumour initiating cells. Nature432(7015), 396–401 (2004).
   PubMed Web of Science ®Google Scholar
• Sledge GW. What is targeted therapy? J. Clin. Oncol.23(8), 1614–1615 (2005).
   PubMed Web of Science ®Google Scholar
• Burgess T, Coxon A, Meyer S et al. Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic potential against hepatocyte growth factor/c-Met-dependent human tumors. Cancer Res.66(3), 1721–1729 (2006).
   PubMed Web of Science ®Google Scholar
• Morrison RS, Yamaguchi F, Saya H et al. Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas. J. Neurooncol.18(3), 207–216 (1994).
   PubMed Web of Science ®Google 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 immunogenecity 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(12), 937–947 (2004).
   PubMedGoogle Scholar
• Koul D, Shen R, Bergh S et al. Inhibition of Akt survival pathway by a small-molecule inhibitor in human glioblastoma. Mol. Cancer Ther.5(3), 637–644 (2006).
   PubMed Web of Science ®Google Scholar
• Fen QW, Knight ZA, Goldenberg DD et al. A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell9, 341–349 (2006).
   PubMedGoogle 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
• Edwards LA, Verreault M, Thiesen B et al. Combined inhibition of the phosphatidylinositol 3-kinase/Akt and Ras/mitogen-activated protein kinase pathways results in synergistic effects in glioblastoma cells. Mol. Cancer Ther.5(3), 645–654 (2006).
   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
• Oltersdorf T, Elmore SW, Shoemaker AR et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumors. 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
• 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(23), 13513–13518 (2003).
   PubMed Web of Science ®Google Scholar
• Pollack IF, Erff M, Ashkenazi A. Direct stimulation of apoptotic signaling by soluble Apo2L/tumor necrosis factor-related apoptosis-inducing ligand leads to selective killing of glioma cells. Clin. Cancer Res.7, 1362–1369 (2001).
   PubMed Web of Science ®Google Scholar
• Wen PY, Kesari S, Drappatz J. Malignant gliomas: strategies to increase the effectiveness of targeted molecular treatment. Expert Rev. Anticancer Ther.6, 733–754 (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
• Rich JN, Reardon DA, Peery T et al. Phase II trial of gefitinib in recurrent glioblastoma. J. Clin. Oncol.22(1), 133–142 (2004).
   PubMed Web of Science ®Google 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, 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, 880–887 (2005).
   PubMed Web of Science ®Google Scholar
• Halatsch ME, Schmidt U, Benhke-Mursch J, Unterberg A, Wirtz CR. Epidermal growth factor receptor inhibition for the treatment of glioblastoma multiforme and other malignant brain tumors. Cancer Treat. Rev.32, 74–89 (2006).
   PubMed Web of Science ®Google Scholar
• Tremont-Lukats IW, Gilbert MR. Advances in molecular therapies in patients with brain tumors. Cancer Control10, 125–137 (2003).
   PubMedGoogle Scholar
• Board R, Jayson GC. Platelet-derived growth factor receptor (PDGFR): a target for anticancer therapeutics. Drug Resist. Updat.8, 75–83 (2005).
   PubMed Web of Science ®Google Scholar
• Wen PY, Yung WKA, Lamborn KR. Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium study 99–108. Clin. Cancer Res.12(16), 4899–4907 (2006).
   PubMed Web of Science ®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. J. Clin. Oncol.22(Suppl. 14), 1501 (2004).
   PubMedGoogle Scholar
• van den Bent M, Stupp R, Brandes AA. Current and future trials of the EORTC Brain Tumor Group. Onkologie27, 246–250 (2004).
   PubMedGoogle 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 [abstract 1517]. J. Clin. Oncol.23, S118 (2005).
   Google Scholar
• Mesa R. Tipifarnib: farnesyl transferase inhibition at a crossroads. Expert Rev. Anticancer Ther.6(3), 313–319 (2006).
   PubMed Web of Science ®Google Scholar
• Cloughesy TF, Wen PY, Robins HI et al. Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium study. J. Clin. Oncol.24, 3651–3656 (2006).
   PubMed Web of Science ®Google Scholar
• Adjei AA, Erlichman C, Davis JN et al. A Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity. Cancer Res.60(7), 1871–1877 (2000).
   PubMed Web of Science ®Google Scholar
• Eskens FA, Awada A, Cutler DL et al. Phase I and pharmacokinetic study of the oral farnesyl transferase inhibitor SCH 66336 given twice daily to patients with advanced solid tumors. J. Clin. Oncol.19(4), 1167–1175 (2001).
   PubMed Web of Science ®Google Scholar
• Awada A, Eskens FA, Piccart M et al. Phase I and pharmacological study of the oral farnesyltransferase inhibitor SCH 66336 given once daily to patients with advanced solid tumours. Eur. J. Cancer38(17), 2272–2278 (2002).
   PubMed Web of Science ®Google Scholar
• Wen PY. Targeted molecular therapies with single agents for malignant gliomas. In: American Society of Clinical Oncology 2005 Educational Book. Perry M (Ed). ASCO, VA, USA 161–167 (2005).
   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(4), 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
• 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
• Sathornsumetee S, Rich JN. New strategies for malignant gliomas. Expert Rev. Anticancer Ther.6(7), 1087–1106 (2006).
   PubMed Web of Science ®Google Scholar
• Conrad C, Friedman H, Reardon D et al. A Phase I/II trial of single-agent PTK 787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor, in patients with resurrent glioblastoma multiforme (GBM). Proc. Am. Soc. Clin. Oncol.22(14), (Suppl. 110), 1512 (2004).
   Web of Science ®Google Scholar
• Fine HA, Kim L, Royce C et al. Results from Phase II trial of enzastaurin (LY317615) in patients with recurrent high grade gliomas. J. Clin. Oncol.23(Suppl. 16), 1504 (2005).
   Google Scholar
• Nabors LB, Rosenfeld SS, Mikkelsen T et al. NABTT 9911: a Phase I trial of EMD 121974 for treatment of patients with recurrent malignant gliomas. Neuro-Oncology6(4), 379 (2004).
   Web of Science ®Google Scholar
• Levin VA, Phuphanich S, Yung WK et al. Randomized, double-blind, placebo-controlled trial of marimastat in glioblastoma multiforme patients following surgery and irradiation. J. Neurooncol.78(3), 295–302 (2006).
   PubMed Web of Science ®Google Scholar
• Boccadoro M, Morgan G, Cavenagh J. Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int.5, 18 (2005).
   PubMed Web of Science ®Google Scholar
• Marks P, Rifkind RA, Richon VM et al. Histone deacetylases and cancer: causes and therapies. Nat. Rev. Cancer1, 194–202 (2001).
   PubMed Web of Science ®Google Scholar
• Reardon DA. Combinatorial approaches using targeted therapeutics for patients with malignant glioma. In: American Society of Clinical Oncology 2005 Educational Book. Perry M (Ed). ASCO, VA, USA 168–173 (2005).
   Google Scholar
• Dancey JE, Chen HX. Strategies for optimizing combinations of molecularly targeted anticancer agents. Nat. Rev. Drug Discov.5, 649–659 (2006).
   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
• Wen PY, Chang SM, Khun J et al. Phase I study of erlotinib (Tarceva) and temsirolimus (CCI-779) from patients with recurrent malignant gliomas (NABTC 04–02). Neuro-Oncology8(4) (2006).
   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, 1383–1388 (2002).
   PubMed Web of Science ®Google Scholar
• Groves MD, Puduvalli VK, Gilbert MR et al. A Phase II study of temozolomide plus marimastat for recurrent anaplastic glioma (AG). Neuro-Oncology4, S369 (2002).
   Google Scholar
• Groves MD, Puduvalli VK, Conrad CA et al. Phase II trial of temozolomide plus marimastat for recurrent anaplastic gliomas: a relationship among efficacy, joint toxicity and anticonvulsant status. J. Neurooncol.80(1), 83–90 (2006).
   PubMed Web of Science ®Google Scholar
• Dresemann G. Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: a patient series. Ann. Oncol.16, 1702–1708 (2005).
   PubMed Web of Science ®Google Scholar
• Reardon DA, Egorin MJ, Quinn JA et al. Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme. J. Clin. Oncol.23, 9359–9368 (2005).
   PubMed Web of Science ®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). Proceedings of the Society for Neuro-oncology 9th Annual Meeting. Neuro-Oncology6, 381 (2004).
   Google Scholar
• Chakravarti A, Berkey B, Robins I et al. An update of Phase II results from RTOG 0211: a Phase I/II study of gefitinib with radiotherapy in newly diagnosed glioblastoma multiforme. Neuro-Oncology8(4), 439 (2006).
   Google Scholar
• Pereboom DM, Brewer CJ, Suh GH et al. Phase II trial of erlotinib with temozolomide and concurrent radiation therapy in patients with newly diagnosed glioblastoma multiforme: final results. Neuro-Oncology8(4) 448 (2006).
   Google Scholar
• Jimeno A, Hidalgo M. Multitargeted therapy: can promiscuity be praised in an era of political correctness? Crit. Rev. Oncol. Hematol.59, 150–158 (2006).
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Hoosen S, Bello CL, Christensen JG. Sunitinib malate for the treatment of solid tumours: a review of current clinical data. Expert Opin. Investig. Drugs15(5), 553–561 (2006).
   PubMed Web of Science ®Google Scholar
• Vredenburgh JJ, Desjardins A, Herndon JE et al. Bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), and irinotecan for treatment of malignant gliomas. J. Clin. Oncol.24(Suppl. 18), 1506 (2006).
   Google Scholar
• Nguyen TD, Lassman AB, Lis E et al. A pilot study to assess the tolerability and efficacy of RAD-001 (everolimus) with gefitinib in patients with recurrent glioblastoma multiforme. J. Clin. Oncol.24(Suppl. 18), 1507 (2006).
   PubMedGoogle Scholar
• Ross BD, Hamstra DA, Chenevert TL et al. Assessment of the functional diffusion map (fDM) as an imaging biomarker for early stratification of glioma clinical response. J. Clin. Oncol.24(Suppl. 18), 1518 (2006).
   Google Scholar
• Pannullo SC, Burton J, Serventi J et al. Phase I/II trial of twice-daily temozolomide and celecoxib for treatment of relapsed malignant glioma: final data. J. Clin. Oncol.24(Suppl. 18), 1519 (2006).
   Google Scholar
• Bode U, Buchen S, Janssen G et al. Results of a Phase II trial of h-R3 monoclonal antibody (nimotuzumab) in the treatment of resistant or relapsed high-grade gliomas in children and adolescents. J. Clin. Oncol.24(Suppl. 18), 1522 (2006).
   PubMedGoogle Scholar
• Marosi C, Vedadinejad M, Haberler C et al. Imatinib mesylate in the treatment of patients with recurrent high grade gliomas expressing PDGF-R. J. Clin. Oncol.24(Suppl. 18), 1526 (2006).
   Google Scholar
• Chakravarti A, Berkey B, Robins HI et al. An update of Phase II results from RTOG 0211: a Phase I/II study of gefitinib with radiotherapy in newly diagnosed glioblastoma. J. Clin. Oncol.24(Suppl. 18), 1527 (2006).
   Google Scholar
• Bogdahn U, Oliushine VE, Parfenov VE et al. Results of G004, a Phase IIb study in recurrent glioblastoma patients with the TGF-β2 targeted compound AP 12009. J. Clin. Oncol.24(Suppl. 18), 1553 (2006).
   Google Scholar
• Gilbert MR, Gaupp P, Liu V et al. A Phase I study of temozolomide (TMZ) and the farnesyltransferase inhibitor (FTI), lonafarnib (Sarazar, SCH66336) in recurrent glioblastoma. J. Clin. Oncol.24(Suppl. 18), 1556 (2006).
   Google Scholar
• Sadones J, Chaskis C, Joosens EJ et al. A stratified Phase II study of cetuximab for the treatment of recurrent glioblastoma multiforme: preliminary results. J. Clin. Oncol.24(Suppl. 18), 1558 (2006).
   Google Scholar
• Sathornsumetee S, Reardon DA, Quinn JA et al. An update on Phase I study of dose-escalating imatinib mesylate plus standard-dosed temozolomide for the treatment of patients with malignant glioma. J. Clin. Oncol.24(Suppl. 18), 1560 (2006).
   Google Scholar
• Puduvalli VK, Giglio P, Groves MD et al. Phase II study of the combination of thalidomide and irinotecan in patients with recurrent anaplastic gliomas not on enzyme inducing anticonvulsants. J. Clin. Oncol.24(Suppl. 18), 1564 (2006).
   Google Scholar
• Hau P, Stockhammer G, Kunst M et al. Results of G004, a Phase IIb actively controlled clinical trial with the TGF-β2 targeted compound AP 12009 for recurrent anaplastic astrocytoma. J. Clin. Oncol.24(Suppl. 18), 1566 (2006).
   Google Scholar
• Phuphanich S, Supko J, Carson KA et al. Phase I trial of bortezomib in adults with recurrent malignant glioma. J. Clin. Oncol.24(Suppl. 18), 1567 (2006).
   Google Scholar
• Desjardins A, Reardon DA, Quinn JA et al. Phase II trial of imatinib mesylate and hydroxyurea for grade III malignant gliomas. J. Clin. Oncol.24(Suppl. 18), 1573 (2006).
   Google Scholar
• Gondi CS, Kandhukuri N, Yanamandra N, Reddy M, Reddy E, Rao JS. Regression of pre-established intracranial tumor growth by ON 01910.Na, a selective anticancer agent currently in Phase I trials. J. Clin. Oncol.24(Suppl. 18), 1576 (2006).
   Google Scholar
• Reardon D, Quinn JA, Rich JN et al. A Phase I trial of imatinib, hydroxyurea and RAD001 for patients with recurrent malignant glioma. J. Clin. Oncol.24(Suppl. 18), 1580 (2006).
   Google Scholar
• Dresemann G, Hosius C, Nikolova Z, Letvak L. Imatinib plus hydroxyurea in pretreated non-progressive glioblastoma (GBM) – a single center Phase II study. J. Clin. Oncol.24(Suppl. 18), 1583 (2006).
   Google Scholar
• Rich JN, Shi Q, Hjelmeland AB et al. A novel low molecular weight inhibitor of focal adhesion kinase and insulin-like growth factor-1 receptor, TAE226, inhibits glioma growth. J. Clin. Oncol.24(Suppl. 18), 11505 (2006).
   Google Scholar
• Eastman A, Perez RP. New targets and challenges in the molecular therapeutics of cancer. Br. J. Clin. Pharmacol.62(1), 5–14 (2006).
   PubMed Web of Science ®Google Scholar
• Lesniak MS, Langer R, Brem H. Drug delivery to tumors of the central nervous system. Curr. Neurol. Neurosci. Rep.1, 210–216 (2001).
   PubMedGoogle 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
• Dai H, Marbach P, Lemaire M, Hayes M, Elmquist WF. Distribution of STI-571 to the brain is limited by P-glycoprotein-mediated efflux. J. Pharmacol. Exp. Ther.304(3), 1085–1092 (2003).
   PubMed Web of Science ®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 (2002).
   PubMedGoogle Scholar
• Gilbert MR. Molecularly targeted therapy for malignant gliomas: an introduction. In: American Society of Clinical Oncology 2005 Educational Book. Perry M (Ed). ASCO, VA, USA 155–160 (2005).
   Google Scholar
• Macdonald DR, Cascino TL, Schold SC, Cairncross JG. Response criteria for Phase II studies of supratentorial malignant glioma. J. Clin. Oncol.8, 1277–1280 (1990).
   PubMed Web of Science ®Google Scholar
• Ballman KV, Buckner JC, Brown PD et al. The relationship between six-month progression-free survival and 12-month overall survival end points for Phase II trials in patients with glioblastoma multiforme. Neuro-Oncology9(1), 29–38 (2007).
   PubMed Web of Science ®Google Scholar
• Moffat BA, Chenevert TL, Lawrence TS et al. Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response. Proc. Natl Acad. Sci. USA102(15), 5524–5529 (2005).
   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
• Barthel H, Cleij MC, Collingridge DR et al. 3´-deoxy-3´-[18F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography. Cancer Res.63(13), 3791–3798 (2003).
   PubMed Web of Science ®Google Scholar
• Leyton J, Alao JP, Da Costa M et al. In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3´-deoxy-3´-[18F]fluorothymidine positron emission tomography. Cancer Res.66(15), 7621–7629 (2006).
   PubMed Web of Science ®Google Scholar
• Pal A, Glekas A, Doubrovin M et al. Molecular imaging of EGFR kinase activity in tumors with 124I-labeled small molecular tracer and positron emission tomography. Mol. Imaging Biol.8(5), 262–277 (2006).
   PubMedGoogle Scholar
• Brunner M, Muller M. Microdialysis: an in vivo approach for measuring drug delivery in oncology. Eur. J. Clin. Pharmacol.58, 227–234 (2002).
   PubMed Web of Science ®Google Scholar
• De Lange E, Danhof M, de Boer AG, Breimer DD. Methodological considerations of intracerebral microdialysis in pharmacokinetic studies on drug transport across the blood–brain barrier. Brain Res. Rev.25, 27–49 (1997).
   PubMed Web of Science ®Google Scholar
• Benjamin RK, Hochberg FH, Fox E et al. Review of microdialysis in brain tumors, from concept to application: First Annual Carolyn Frye-Halloran Symposium. Neuro-Oncology6, 65–74 (2004).
   PubMed Web of Science ®Google Scholar
• Thall PF. Ethical issues in oncology biostatistics. Stat. Methods Med. Res.11, 429–448 (2002).
   PubMedGoogle Scholar
• Berry DA, Eick SG: Adaptive assignment versus balanced randomization in clinical trials: a decision analysis. Stat. Med.14, 231–246 (1994).
   Web of Science ®Google Scholar
• Thall PF, Inoue L, Berry DA. Seamlessly expanding a randomized Phase II trial to Phase III. Biometrics58, 823–831 (2002).
   PubMedGoogle Scholar
• Phillips HS, Kharbanda S, Chen R et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell9, 157–173 (2006).
   PubMed Web of Science ®Google Scholar
• Aldape KL, Zhang L, Phillips H et al. Meta-analysis of gene expression profiling data from glioblastoma tumor samples identifies a robust multigene classifier predictive of survival. Neuro-Oncology8(4) (2006).
   Google Scholar