Investigational new drugs for brain cancer

References

• Ostrom QT, Gittleman H, Fulop J, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro Oncol. 2015;17(Suppl 4):iv1–iv62. doi:10.1093/neuonc/nov189.
   PubMed Web of Science ®Google Scholar
• Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109. doi:10.1007/s00401-007-0243-4.
   PubMed Web of Science ®Google Scholar
• Ohgaki H, Kleihues P. Genetic pathways to primary and secondary glioblastoma. Am J Pathol. 2007;170(5):1445–1453. doi:10.2353/ajpath.2007.070011.
   PubMed Web of Science ®Google Scholar
• Jenkins RB, Blair H, Ballman KV, et al. A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res. 2006;66(20):9852–9861. doi:10.1158/0008-5472.CAN-06-1796.
   PubMed Web of Science ®Google Scholar
• Ostrom QT, De Blank PM, Kruchko C, et al. Alex’s lemonade stand foundation infant and childhood primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro Oncol. 2015;16(Suppl 10):x1–x36. doi:10.1093/neuonc/nou327.
   PubMed Web of Science ®Google Scholar
• Fangusaro J. Pediatric high grade glioma: a review and update on tumor clinical characteristics and biology. Front Oncol. 2012;2:105. doi:10.3389/fonc.2012.00105.
   PubMedGoogle Scholar
• Warren KE. Diffuse intrinsic pontine glioma: poised for progress. Front Oncol. 2012;2:205. doi:10.3389/fonc.2012.00205.
   PubMedGoogle Scholar
• Jones C, Baker SJ. Unique genetic and epigenetic mechanisms driving paediatric diffuse high-grade glioma. Nat Rev Cancer. 2014;14(10). doi:10.1038/nrc3811.
   Web of Science ®Google Scholar
• Cage TA, Samagh SP, Mueller S, et al. Feasibility, safety, and indications for surgical biopsy of intrinsic brainstem tumors in children. Childs Nerv Syst . 2013;29(8):1313–1319. doi:10.1007/s00381-013-2101-0.
   PubMed Web of Science ®Google Scholar
• Farrell CJ, Plotkin SR. Genetic causes of brain tumors: neurofibromatosis, tuberous sclerosis, von Hippel-Lindau, and other syndromes. Neurol Clin. 2007;25(4):925–46, viii. doi:10.1016/j.ncl.2007.07.008.
   PubMed Web of Science ®Google Scholar
• Cairncross JG, Wang M, Jenkins RB, et al. Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. J Clin Oncol. 2014;32(8):783–790. doi:10.1200/JCO.2013.49.3726.
   PubMed Web of Science ®Google Scholar
• van den Bent MJ, Brandes AA, Taphoorn MJ, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013;31(3):344–350. doi:10.1200/JCO.2012.43.2229.
   PubMed Web of Science ®Google Scholar
• Chaichana KL, Jusue-Torres I, Navarro-Ramirez R, et al. Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro Oncol. 2014;16(1):113–122. doi:10.1093/neuonc/not137.
   PubMed Web of Science ®Google Scholar
• Sanai N, Polley MY, McDermott MW, et al. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg. 2011;115(1):3–8. doi:10.3171/2011.2.JNS10998.
   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. 2005;352(10):987–996. doi:10.1056/NEJMoa043330.
   PubMed Web of Science ®Google Scholar
• Esteller M, Hamilton SR, Burger PC, et al. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res. 1999;59(4):793–797.
   PubMed Web of Science ®Google Scholar
• Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997–1003. doi:10.1056/NEJMoa043331.
   PubMed Web of Science ®Google Scholar
• Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):699–708. doi:10.1056/NEJMoa1308573.
   PubMed Web of Science ®Google Scholar
• Cohen MH, Shen YL, Keegan P, et al. FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist. 2009;14(11):1131–1138. doi:10.1634/theoncologist.2009-0121.
   PubMed Web of Science ®Google Scholar
• Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709–722. doi:10.1056/NEJMoa1308345.
   PubMed Web of Science ®Google Scholar
• Cohen KJ, Pollack IF, Zhou T, et al. Temozolomide in the treatment of high-grade gliomas in children: a report from the children’s oncology group. Neuro Oncol. 2011;13(3):317–323. doi:10.1093/neuonc/noq191.
   PubMed Web of Science ®Google Scholar
• van den Bent MJ, Brandes AA, Rampling R, et al. Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol. 2009;27(8):1268–1274. doi:10.1200/JCO.2008.17.5984.
   PubMed Web of Science ®Google Scholar
• Prados MD, Chang SM, Butowski N, et al. Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. J Clin Oncol. 2009;27(4):579–584. doi:10.1200/JCO.2008.18.9639.
   PubMed Web of Science ®Google Scholar
• Wen PY, Chang SM, Lamborn KR, et al. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American brain tumor consortium trial 04-02. Neuro Oncol. 2014;16(4):567–578. doi:10.1093/neuonc/not247.
   PubMed Web of Science ®Google Scholar
• Uhm JH, Ballman KV, Wu W, et al. Phase II evaluation of gefitinib in patients with newly diagnosed grade 4 astrocytoma: Mayo/North central cancer treatment group study N0074. Int J Radiat Oncol Biol Phys. 2011;80(2):347–353. doi:10.1016/j.ijrobp.2010.01.070.
   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. 2004;22(1):133–142. doi:10.1200/JCO.2004.08.110.
   PubMed Web of Science ®Google Scholar
• Chakravarti A, Wang M, Robins HI, et al. RTOG 0211: a phase 1/2 study of radiation therapy with concurrent gefitinib for newly diagnosed glioblastoma patients. Int J Radiat Oncol Biol Phys. 2013;85(5):1206–1211. doi:10.1016/j.ijrobp.2012.10.008.
   PubMed Web of Science ®Google Scholar
• Prados MD, Yung WK, Wen PY, et al. Phase-1 trial of gefitinib and temozolomide in patients with malignant glioma: a North American brain tumor consortium study. Cancer Chemother Pharmacol. 2008;61(6):1059–1067. doi:10.1007/s00280-007-0556-y.
   PubMed Web of Science ®Google Scholar
• Thiessen B, Stewart C, Tsao M, et al. A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation. Cancer Chemother Pharmacol. 2010;65(2):353–361. doi:10.1007/s00280-009-1041-6.
   PubMed Web of Science ®Google Scholar
• Fouladi M, Stewart CF, Blaney SM, et al. A molecular biology and phase II trial of lapatinib in children with refractory CNS malignancies: a pediatric brain tumor consortium study. J Neurooncol. 2013;114(2):173–179. doi:10.1007/s11060-013-1166-7.
   PubMed Web of Science ®Google Scholar
• Reardon DA, Groves MD, Wen PY, et al. A phase I/II trial of pazopanib in combination with lapatinib in adult patients with relapsed malignant glioma. Clin Cancer Res. 2013;19(4):900–908. doi:10.1158/1078-0432.CCR-12-1707.
   PubMed Web of Science ®Google Scholar
• Combs SE, Heeger S, Haselmann R, et al. Treatment of primary glioblastoma multiforme with cetuximab, radiotherapy and temozolomide (GERT)–phase I/II trial: study protocol. BMC Cancer. 2006;6:133. doi:10.1186/1471-2407-6-133.
   PubMed Web of Science ®Google Scholar
• Reardon DA, Nabors LB, Mason WP, et al. Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma. Neuro Oncol. 2015;17(3):430–439. doi:10.1093/neuonc/nou160.
   PubMed Web of Science ®Google Scholar
• Wen PY, Yung WK, Lamborn KR, et al. Phase I/II study of imatinib mesylate for recurrent malignant gliomas: north American brain tumor consortium study 99-08. Clin Cancer Res. 2006;12(16):4899–4907. doi:10.1158/1078-0432.CCR-06-0773.
   PubMed Web of Science ®Google Scholar
• Reardon DA, Desjardins A, Vredenburgh JJ, et al. Safety and pharmacokinetics of dose-intensive imatinib mesylate plus temozolomide: phase 1 trial in adults with malignant glioma. Neuro Oncol. 2008;10(3):330–340. doi:10.1215/15228517-2008-003.
   PubMed Web of Science ®Google Scholar
• Reardon DA, Dresemann G, Taillibert S, et al. Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma. Br J Cancer. 2009;101(12):1995–2004. doi:10.1038/sj.bjc.6605411.
   PubMed Web of Science ®Google Scholar
• Pan E, Yu D, Yue B, et al. A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. J Neurooncol. 2012;110(1):111–118. doi:10.1007/s11060-012-0943-z.
   PubMed Web of Science ®Google Scholar
• Balana C, Gil MJ, Perez P, et al. Sunitinib administered prior to radiotherapy in patients with non-resectable glioblastoma: results of a phase II study. Target Oncol. 2014;9(4):321–329. doi:10.1007/s11523-014-0305-1.
   PubMed Web of Science ®Google Scholar
• Reardon DA, Vredenburgh JJ, Desjardins A, et al. Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma. J Neurooncol. 2011;101(1):57–66. doi:10.1007/s11060-010-0217-6.
   PubMed Web of Science ®Google Scholar
• Hottinger AF, Aissa AB, Espeli V, et al. Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma. Br J Cancer. 2014;110(11):2655–2661. doi:10.1038/bjc.2014.209.
   PubMed Web of Science ®Google Scholar
• Galanis E, Anderson SK, Lafky JM, et al. Phase II study of bevacizumab in combination with sorafenib in recurrent glioblastoma (N0776): a north central cancer treatment group trial. Clin Cancer Res. 2013;19(17):4816–4823. doi:10.1158/1078-0432.CCR-13-0708.
   PubMed Web of Science ®Google Scholar
• Iwamoto FM, Lamborn KR, Robins HI, et al. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American brain tumor consortium study 06-02). Neuro Oncol. 2010;12(8):855–861. doi:10.1093/neuonc/noq025.
   PubMed Web of Science ®Google Scholar
• Gerstner ER, Eichler AF, Plotkin SR, et al. Phase I trial with biomarker studies of vatalanib (PTK787) in patients with newly diagnosed glioblastoma treated with enzyme inducing anti-epileptic drugs and standard radiation and temozolomide. J Neurooncol. 2011;103(2):325–332. doi:10.1007/s11060-010-0390-7.
   PubMed Web of Science ®Google Scholar
• Reardon DAPE, Fan J, Mink J, et al. A phase 2 trial of the multitargeted kinase inhibitor lenvatinib (E7080) in patients (pts) with recurrent glioblastoma (GBM) and disease progression [Internet]. ESMO Congress. 2012 [cited 2012 Sep 29]. Available from: http://oncologypro.esmo.org/Meeting-Resources/ESMO-2012/A-phase-2-trial-of-the-multitargeted-kinase-inhibitor-lenvatinib-E7080-in-patients-pts-with-recurrent-glioblastoma-GBM-and-disease-progression-following-prior-bevacizumab-treatment
   Google Scholar
• Lassman AB, Pugh SL, Gilbert MR, et al. Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627). Neuro Oncol. 2015;17(7):992–998. doi:10.1093/neuonc/nov011.
   PubMed Web of Science ®Google Scholar
• Laack NNGE, Anderson SK, Leinweber C, et al. Randomized, placebo-controlled, phase II study of dasatinib with standard chemo-radiotherapy for newly diagnosed glioblastoma (GBM), NCCTG N0877 (Alliance). ASCO Meeting abstract. J Clin Oncol. 2015;33(suppl; abstr 2013).
   Google Scholar
• Franceschi E, Stupp R, van den Bent MJ, et al. EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma. Neuro Oncol. 2012;14(12):1503–1510. doi:10.1093/neuonc/nos256.
   PubMed Web of Science ®Google Scholar
• Wen PY, Schiff D, Cloughesy TF, et al. A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastoma. Neuro Oncol. 2011;13(4):437–446. doi:10.1093/neuonc/noq198.
   PubMed Web of Science ®Google Scholar
• Wen PY. American Society of Clinical Oncology 2010: report of selected studies from the CNS tumors section. Expert Rev Anticancer Ther. 2010;10(9):1367–1369. doi:10.1586/era.10.117.
   PubMedGoogle Scholar
• Schiff D, Desjardins A, Cloughesy T, et al. Phase 1 dose escalation trial of the safety and pharmacokinetics of cabozantinib concurrent with temozolomide and radiotherapy or temozolomide after radiotherapy in newly diagnosed patients with high-grade gliomas. Cancer. 2015. DOI:10.1002/cncr.29798.
   Web of Science ®Google Scholar
• Fields EC, Damek D, Gaspar LE, et al. Phase I dose escalation trial of vandetanib with fractionated radiosurgery in patients with recurrent malignant gliomas. Int J Radiat Oncol Biol Phys. 2012;82(1):51–57. doi:10.1016/j.ijrobp.2010.09.008.
   PubMed Web of Science ®Google Scholar
• Broniscer A, Baker SD, Wetmore C, et al. Phase I trial, pharmacokinetics, and pharmacodynamics of vandetanib and dasatinib in children with newly diagnosed diffuse intrinsic pontine glioma. Clin Cancer Res. 2013;19(11):3050–3058. doi:10.1158/1078-0432.CCR-13-0306.
   PubMed Web of Science ®Google Scholar
• Drappatz J, Norden AD, Wong ET, et al. Phase I study of vandetanib with radiotherapy and temozolomide for newly diagnosed glioblastoma. Int J Radiat Oncol Biol Phys. 2010;78(1):85–90. doi:10.1016/j.ijrobp.2009.07.1741.
   PubMed Web of Science ®Google Scholar
• Neyns B, Duerinck J, Du Four S, et al. Randomized phase II study of axitinib versus standard of care in patients with recurrent glioblastoma. J Clin Oncol. 2014;(suppl; abstr 2018).
   PubMed Web of Science ®Google Scholar
• Sarkaria JN, Galanis E, Wu W, et al. Combination of temsirolimus (CCI-779) with chemoradiation in newly diagnosed glioblastoma multiforme (GBM) (NCCTG trial N027D) is associated with increased infectious risks. Clin Cancer Res. 2010;16(22):5573–5580. doi:10.1158/1078-0432.CCR-10-1453.
   PubMed Web of Science ®Google Scholar
• Lee EQ, Puduvalli VK, Reid JM, et al. Phase I study of vorinostat in combination with temozolomide in patients with high-grade gliomas: north American brain tumor consortium study 04-03. Clin Cancer Res. 2012;18(21):6032–6039. doi:10.1158/1078-0432.CCR-12-1841.
   PubMed Web of Science ®Google Scholar
• Weller M, Gorlia T, Cairncross JG, et al. Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma. Neurology. 2011;77(12):1156–1164. doi:10.1212/WNL.0b013e31822f02e1.
   PubMed Web of Science ®Google Scholar
• Heimberger A, Hussain S, Aldape K, et al. Tumor-specific peptide vaccination in newly-diagnosed patients with GBM. J Clin Oncol. 2006;24:107S–07S.
   Web of Science ®Google Scholar
• Sampson JH, Aldape KD, Archer GE, et al. Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. Neuro Oncol. 2011;13(3):324–333. doi:10.1093/neuonc/noq157.
   PubMed Web of Science ®Google Scholar
• Schuster J, Lai RK, Recht LD, et al. A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study. Neuro Oncol. 2015;17(6):854–861. doi:10.1093/neuonc/nou348.
   PubMed Web of Science ®Google Scholar
• Celldex. 2016. Data Safety and Monitoring Board Recommends Celldex’s Phase 3 Study of RINTEGA® (rindopepimut) in Newly Diagnosed Glioblastoma be Discontinued as it is Unlikely to Meet Primary Overall Survival Endpoint in Patients with Minimal Residual Disease. Secondary Data Safety and Monitoring Board Recommends Celldex’s Phase 3 Study of RINTEGA® (rindopepimut) in Newly Diagnosed Glioblastoma be Discontinued as it is Unlikely to Meet Primary Overall Survival Endpoint in Patients with Minimal Residual Disease. Available from: http://ir.celldex.com/releasedetail.cfm?ReleaseID=959021
   Google Scholar
• Reardon D, Schuster J, Tran DD, et al. ReACT: overall survival from a randomized phase II study of rindopepimut (CDX-110) plus bevacizumab in relapsed glioblastoma. J Clin Oncol. 2015;33(suppl; abstr 2009)
   Google Scholar
• Wen PY, Reardon D, Phuphanich S, et al. A randomized double blind placebo-controlled phase 2 trial of dendritic (DC) cell vaccine ICT-107 following standard treatment in newly diagnosed patients with GBM. Neuro Oncol. 2014;16(5):v22. doi:10.1093/neuonc/nou237.59
   Google Scholar
• Orin Bloch O, Raizer JJ, Lim M, et al. Newly diagnosed glioblastoma patients treated with an autologous heat shock protein peptide vaccine: PD-L1 expression and response to therapy. J Clin Oncol. 2015;33(suppl; abstr 2011).
   Google Scholar
• Bloch O, Crane CA, Fuks Y, et al. Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial. Neuro Oncol. 2014;16(2):274–279. doi:10.1093/neuonc/not203.
   PubMed Web of Science ®Google Scholar
• Xu LW, Chow KK, Lim M, et al. Current vaccine trials in glioblastoma: a review. J Immunol Res. 2014;2014:796856. doi:10.1155/2014/796856.
   PubMed Web of Science ®Google Scholar
• Lang F, Conrad C, Gomez-Manzano C, et al. Phase I clinical trial of oncolytic virus Delta-24-RGD (DNX-2401) with biological endpoints: implications for viro-immunotherapy. Neuro Oncol. 2014;16(3_suppl):iii39. doi:10.1093/neuonc/nou208.61.
   Google Scholar
• Markert JM, Medlock MD, Rabkin SD, et al. Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Ther. 2000;7(10):867–874. doi:10.1038/sj.gt.3301205.
   PubMed Web of Science ®Google Scholar
• Markert JM, Razdan SN, Kuo HC, et al. A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. Mol Ther. 2014;22(5):1048–1055. doi:10.1038/mt.2014.22.
   PubMed Web of Science ®Google Scholar
• Kicielinski KP, Chiocca EA, Yu JS, et al. Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. Mol Ther. 2014;22(5):1056–1062. doi:10.1038/mt.2014.21.
   PubMed Web of Science ®Google Scholar
• Desjardins A, Sampson JH, Peters KB, et al. Oncolytic polio/rhinovirus recombinant (pvsripo) in recurrent glioblastoma (gbm): first Phase I clinical trial evaluating the intratumoral administration. Neuro Oncol. 2014;16(3_suppl):iii43. doi:10.1093/neuonc/nou209.5
   Web of Science ®Google Scholar
• Cancer Genome Atlas Research N. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455(7216): 1061–1068. doi:10.1038/nature07385.
   PubMed Web of Science ®Google Scholar
• Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807–1812. doi:10.1126/science.1164382.
   PubMed Web of Science ®Google Scholar
• Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2000;103(2):211–225.
   PubMed Web of Science ®Google Scholar
• Carrasco-Garcia E, Saceda M, Martinez-Lacaci I. Role of receptor tyrosine kinases and their ligands in glioblastoma. Cells. 2014;3(2):199–235. doi:10.3390/cells3020199.
   PubMedGoogle Scholar
• Li Y, Li A, Glas M, et al. C-MET signaling induces a reprogramming network and supports the glioblastoma stem-like phenotype. Proc Natl Acad Sci U S A. 2011;108(24):9951–9956. doi:10.1073/pnas.1016912108.
   PubMed Web of Science ®Google Scholar
• Heimberger AB, Hlatky R, Suki D, et al. Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res. 2005;11(4):1462–1466. doi:10.1158/1078-0432.CCR-04-1737.
   PubMed Web of Science ®Google Scholar
• Siegelin MD, Borczuk AC. Epidermal growth factor receptor mutations in lung adenocarcinoma. Lab Invest. 2014;94(2):129–137. doi:10.1038/labinvest.2013.147.
   PubMed Web of Science ®Google Scholar
• De Witt Hamer PC. Small molecule kinase inhibitors in glioblastoma: a systematic review of clinical studies. Neuro Oncol. 2010;12(3):304–316. doi:10.1093/neuonc/nop068.
   PubMed Web of Science ®Google Scholar
• Reardon DA, Desjardins A, Vredenburgh JJ, et al. Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J Neurooncol. 2010;96(2):219–230. doi:10.1007/s11060-009-9950-0.
   PubMed Web of Science ®Google Scholar
• Lee JC, Vivanco I, Beroukhim R, et al. Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain. PLoS Med. 2006;3(12):e485. doi:10.1371/journal.pmed.0030485.
   PubMed Web of Science ®Google Scholar
• Karavasilis V, Kotoula V, Pentheroudakis G, et al. A phase I study of temozolomide and lapatinib combination in patients with recurrent high-grade gliomas. J Neurol. 2013;260(6):1469–1480. doi:10.1007/s00415-012-6812-z.
   PubMed Web of Science ®Google Scholar
• Greenall SA, Donoghue JF, Gottardo NG, et al. Glioma-specific Domain IV EGFR cysteine mutations promote ligand-induced covalent receptor dimerization and display enhanced sensitivity to dacomitinib in vivo. Oncogene. 2015;34(13):1658–1666. doi:10.1038/onc.2014.106.
   PubMed Web of Science ®Google Scholar
• Gan HKPK, Fichtel L, Lassman AB, et al. Phase I study of ABT-414 mono- or combination therapy with temozolomide (TMZ) in recurrent glioblastoma (GBM). J Clin Oncology, 2015 ASCO Annu Meet 2015. 2015;2016(15_suppl):33. May 20 Supplement.
   Google Scholar
• Brennan CW, Verhaak RG, McKenna A, et al. The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462–477. doi:10.1016/j.cell.2013.09.034.
   PubMed Web of Science ®Google Scholar
• Razis E, Selviaridis P, Labropoulos S, et al. Phase II study of neoadjuvant imatinib in glioblastoma: evaluation of clinical and molecular effects of the treatment. Clin Cancer Res. 2009;15(19):6258–6266. doi:10.1158/1078-0432.CCR-08-1867.
   PubMed Web of Science ®Google Scholar
• Lu-Emerson C, Norden AD, Drappatz J, et al. Retrospective study of dasatinib for recurrent glioblastoma after bevacizumab failure. J Neurooncol. 2011;104(1):287–291. doi:10.1007/s11060-010-0489-x.
   PubMed Web of Science ®Google Scholar
• Nehoff H, Parayath NN, McConnell MJ, et al. A combination of tyrosine kinase inhibitors, crizotinib and dasatinib for the treatment of glioblastoma multiforme. Oncotarget. 2015;6(35):37948–37964. doi:10.18632/oncotarget.5698.
   PubMed Web of Science ®Google Scholar
• Schiff D, Sarkaria J. Dasatinib in recurrent glioblastoma: failure as a teacher. Neuro Oncol. 2015;17(7):910–911. doi:10.1093/neuonc/nov086.
   PubMed Web of Science ®Google Scholar
• Chen Y, Agarwal S, Shaik NM, et al. P-glycoprotein and breast cancer resistance protein influence brain distribution of dasatinib. J Pharmacol Exp Ther. 2009;330(3):956–963. doi:10.1124/jpet.109.154781.
   PubMed Web of Science ®Google Scholar
• Agarwal S, Mittapalli RK, Zellmer DM, et al. Active efflux of Dasatinib from the brain limits efficacy against murine glioblastoma: broad implications for the clinical use of molecularly targeted agents. Mol Cancer Ther. 2012;11(10):2183–2192. doi:10.1158/1535-7163.MCT-12-0552.
   PubMed Web of Science ®Google Scholar
• Trusolino L, Bertotti A, Comoglio PM. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol. 2010;11(12):834–848. doi:10.1038/nrm3012.
   PubMed Web of Science ®Google Scholar
• Abounader R, Laterra J. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol. 2005;7(4):436–451. doi:10.1215/S1152851705000050.
   PubMed Web of Science ®Google Scholar
• Murray DW, Didier S, Chan A, et al. Guanine nucleotide exchange factor Dock7 mediates HGF-induced glioblastoma cell invasion via Rac activation. Br J Cancer. 2014;110(5):1307–1315. doi:10.1038/bjc.2014.39.
   PubMed Web of Science ®Google Scholar
• Kim KJ, Wang L, Su YC, et al. Systemic anti-hepatocyte growth factor monoclonal antibody therapy induces the regression of intracranial glioma xenografts. Clin Cancer Res. 2006;12(4):1292–1298. doi:10.1158/1078-0432.CCR-05-1793.
   PubMed Web of Science ®Google Scholar
• Chamberlain MC. Bevacizumab for the treatment of recurrent glioblastoma. Clin Med Insights Oncol. 2011;5:117–29. doi:10.4137/CMO.S7232.
   PubMedGoogle Scholar
• Wick WBA, Gorlia T, Bendszus M, et al. Phase III trial exploring the combination of bevacizumab and lomustine in patients with first recurrence of a glioblastoma: THE EORTC 26101 TRIAL. Neuro Oncol. 2015;17:(5_suppl):v1. doi:10.1093/neuonc/nov306.
   Google Scholar
• Zustovich F, Landi L, Lombardi G, et al. Sorafenib plus daily low-dose temozolomide for relapsed glioblastoma: a phase II study. Anticancer Res. 2013;33(8):3487–3494.
   PubMed Web of Science ®Google Scholar
• Lee EQ, Kuhn J, Lamborn KR, et al. Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: north American brain tumor consortium study 05-02. Neuro Oncol. 2012;14(12):1511–1518. doi:10.1093/neuonc/nos264.
   PubMed Web of Science ®Google Scholar
• Peereboom DM, Ahluwalia MS, Ye X, et al. NABTT 0502: a phase II and pharmacokinetic study of erlotinib and sorafenib for patients with progressive or recurrent glioblastoma multiforme. Neuro Oncol. 2013;15(4):490–496. doi:10.1093/neuonc/nos322.
   PubMed Web of Science ®Google Scholar
• Batchelor TT, Duda DG, Di Tomaso E, et al. Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol. 2010;28(17):2817–2823. doi:10.1200/JCO.2009.26.3988.
   PubMed Web of Science ®Google Scholar
• Batchelor TT, Mulholland P, Neyns B, et al. Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol. 2013;31(26):3212–3218. doi:10.1200/JCO.2012.47.2464.
   PubMed Web of Science ®Google Scholar
• Furnari FB, Cloughesy TF, Cavenee WK, et al. Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma. Nat Rev Cancer. 2015;15(5):302–310. doi:10.1038/nrc3918.
   PubMed Web of Science ®Google Scholar
• Szerlip NJ, Pedraza A, Chakravarty D, et al. Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. Proc Natl Acad Sci U S A. 2012;109(8):3041–3046. doi:10.1073/pnas.1114033109.
   PubMed Web of Science ®Google Scholar
• Cloughesy TF, Yoshimoto K, Nghiemphu P, et al. Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med. 2008;5(1):e8. doi:10.1371/journal.pmed.0050008.
   PubMed Web of Science ®Google Scholar
• Chinnaiyan P, Won M, Wen PY, et al. RTOG 0913: a phase 1 study of daily everolimus (RAD001) in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. Int J Radiat Oncol Biol Phys. 2013;86(5):880–884. doi:10.1016/j.ijrobp.2013.04.036.
   PubMed Web of Science ®Google Scholar
• Sarkaria JN, Galanis E, Wu W, et al. North Central Cancer Treatment Group Phase I trial N057K of everolimus (RAD001) and temozolomide in combination with radiation therapy in patients with newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2011;81(2):468–475. doi:10.1016/j.ijrobp.2010.05.064.
   PubMed Web of Science ®Google Scholar
• Hainsworth JD, Shih KC, Shepard GC, et al. Phase II study of concurrent radiation therapy, temozolomide, and bevacizumab followed by bevacizumab/everolimus as first-line treatment for patients with glioblastoma. Clin Adv Hematol Oncol. 2012;10(4):240–246.
   PubMedGoogle 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. 2005;23(23):5294–5304. doi:10.1200/JCO.2005.23.622.
   PubMed Web of Science ®Google Scholar
• Ma DJ, Galanis E, Anderson SK, et al. A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K. Neuro Oncol. 2015;17(9):1261–1269. doi:10.1093/neuonc/nou328.
   PubMed Web of Science ®Google Scholar
• Lassen U, Sorensen M, Gaziel TB, et al. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Anticancer Res. 2013;33(4):1657–1660.
   PubMed Web of Science ®Google Scholar
• Koul D, Fu J, Shen R, et al. Antitumor activity of NVP-BKM120–a selective pan class I PI3 kinase inhibitor showed differential forms of cell death based on p53 status of glioma cells. Clin Cancer Res. 2012;18(1):184–195. doi:10.1158/1078-0432.CCR-11-1558.
   PubMed Web of Science ®Google Scholar
• Koul D, Shen R, Kim YW, et al. Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma. Neuro Oncol. 2010;12(6):559–569. doi:10.1093/neuonc/nop058.
   PubMed Web of Science ®Google Scholar
• Nicolaides TP, Li H, Solomon DA, et al. Targeted therapy for BRAFV600E malignant astrocytoma. Clin Cancer Res. 2011;17(24):7595–7604. doi:10.1158/1078-0432.CCR-11-1456.
   PubMed Web of Science ®Google Scholar
• Penman CL, Faulkner C, Lowis SP, et al. Current understanding of BRAF alterations in diagnosis, prognosis, and therapeutic targeting in pediatric low-grade gliomas. Front Oncol. 2015;5:54. doi:10.3389/fonc.2015.00054.
   PubMed Web of Science ®Google Scholar
• Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–2516. doi:10.1056/NEJMoa1103782.
   PubMed Web of Science ®Google Scholar
• Rochet NM, Dronca RS, Kottschade LA, et al. Melanoma brain metastases and vemurafenib: need for further investigation. Mayo Clin Proc. 2012;87(10):976–981. doi:10.1016/j.mayocp.2012.07.006.
   PubMed Web of Science ®Google Scholar
• Robinson GW, Orr BA, Gajjar A. Complete clinical regression of a BRAF V600E-mutant pediatric glioblastoma multiforme after BRAF inhibitor therapy. BMC Cancer. 2014;14:258. doi:10.1186/1471-2407-14-258.
   PubMed Web of Science ®Google Scholar
• Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694–1703. doi:10.1056/NEJMoa1210093.
   PubMed Web of Science ®Google Scholar
• Nazarian R, Shi H, Wang Q, et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010;468(7326):973–977. doi:10.1038/nature09626.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Adjei AA. The clinical development of MEK inhibitors. Nat Rev Clin Oncol. 2014;11(7):385–400. doi:10.1038/nrclinonc.2014.83.
   PubMed Web of Science ®Google Scholar
• Widemann BCML, Fisher MJ, Weiss BA, et al., Phase I study of the MEK1/2 inhibitor selumetinib (AZD6244) hydrogen sulfate in children and young adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). J Clin Oncol. 2014;32:5s. (suppl; abstr 10018)
   Google Scholar
• Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765–773. doi:10.1056/NEJMoa0808710.
   PubMed Web of Science ®Google Scholar
• Hartmann C, Meyer J, Balss J, et al. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol. 2009;118(4):469–474. doi:10.1007/s00401-009-0561-9.
   PubMed Web of Science ®Google Scholar
• Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462(7274):739–744. doi:10.1038/nature08617.
   PubMed Web of Science ®Google Scholar
• Fathi AT, Abdel-Wahab O. Mutations in epigenetic modifiers in myeloid malignancies and the prospect of novel epigenetic-targeted therapy. Adv Hematol. 2012;2012:469592. doi:10.1155/2012/469592.
   PubMedGoogle Scholar
• Borodovsky A, Salmasi V, Turcan S, et al. 5-azacytidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft. Oncotarget. 2013;4(10):1737–1747. doi:10.18632/oncotarget.1408.
   PubMed Web of Science ®Google Scholar
• Turcan S, Fabius AW, Borodovsky A, et al. Efficient induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT Inhibitor Decitabine. Oncotarget. 2013;4(10):1729–1736. doi:10.18632/oncotarget.1412.
   PubMed Web of Science ®Google Scholar
• Rohle D, Popovici-Muller J, Palaskas N, et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013;340(6132):626–630. doi:10.1126/science.1236062.
   PubMed Web of Science ®Google Scholar
• Davis M, Pragani R, Popovici-Muller J, et al. ML309: a potent inhibitor of R132H mutant IDH1 capable of reducing 2-hydroxyglutarate production in U87 MG glioblastoma cells. Probe reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010 [updated 2013 May 8]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23905201
   Google Scholar
• AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. The premier international meeting featuring novel cancer therapeutics; 2015 Nov 5–9; Boston, MA.
   Google Scholar
• Ferriero R, Iannuzzi C, Manco G, et al. Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate. J Inherit Metab Dis. 2015;38(5):895–904. doi:10.1007/s10545-014-9808-2.
   PubMed Web of Science ®Google Scholar
• Michelakis ED, Sutendra G, Dromparis P, et al. Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med. 2010;2(31):31ra34. doi:10.1126/scitranslmed.3000677.
   PubMed Web of Science ®Google Scholar
• Tonjes M, Barbus S, Park YJ, et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat Med. 2013;19(7):901–908. doi:10.1038/nm.3217.
   PubMed Web of Science ®Google Scholar
• Sokolovic M, Wehkamp D, Sokolovic A, et al. Fasting induces a biphasic adaptive metabolic response in murine small intestine. BMC Genomics. 2007;8:361. doi:10.1186/1471-2164-8-361.
   PubMed Web of Science ®Google Scholar
• Champ CE, Palmer JD, Volek JS, et al. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J Neurooncol. 2014;117(1):125–131. doi:10.1007/s11060-014-1362-0.
   PubMed Web of Science ®Google Scholar
• Schwartz K, Chang HT, Nikolai M, et al. Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature. Cancer Metab. 2015;3:3. doi:10.1186/s40170-015-0129-1.
   PubMed Web of Science ®Google Scholar
• Rieger J, Bahr O, Maurer GD, et al. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma. Int J Oncol. 2014;44(6):1843–1852. doi:10.3892/ijo.2014.2382.
   PubMed Web of Science ®Google Scholar
• Mashimo T, Pichumani K, Vemireddy V, et al. Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. Cell. 2014;159(7):1603–1614. doi:10.1016/j.cell.2014.11.025.
   PubMed Web of Science ®Google Scholar
• Comerford SA, Huang Z, Du X, et al. Acetate dependence of tumors. Cell. 2014;159(7):1591–1602. doi:10.1016/j.cell.2014.11.020.
   PubMed Web of Science ®Google Scholar
• Wade PA. Transcriptional control at regulatory checkpoints by histone deacetylases: molecular connections between cancer and chromatin. Hum Mol Genet. 2001;10(7):693–698.
   PubMed Web of Science ®Google Scholar
• Lin HY, Chen CS, Lin SP, et al. Targeting histone deacetylase in cancer therapy. Med Res Rev. 2006;26(4):397–413. doi:10.1002/med.20056.
   PubMed Web of Science ®Google Scholar
• Eyupoglu IY, Hahnen E, Buslei R, et al. Suberoylanilide hydroxamic acid (SAHA) has potent anti-glioma properties in vitro, ex vivo and in vivo. J Neurochem. 2005;93(4):992–999. doi:10.1111/j.1471-4159.2005.03098.x.
   PubMed Web of Science ®Google Scholar
• Yin D, Ong JM, Hu J, et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor: effects on gene expression and growth of glioma cells in vitro and in vivo. Clin Cancer Res. 2007;13(3):1045–1052. doi:10.1158/1078-0432.CCR-06-1261.
   PubMed Web of Science ®Google Scholar
• Lucio-Eterovic AK, Cortez MA, Valera ET, et al. Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas. BMC Cancer. 2008;8:243. doi:10.1186/1471-2407-8-243.
   PubMed Web of Science ®Google Scholar
• Drappatz J, Lee EQ, Hammond S, et al. Phase I study of panobinostat in combination with bevacizumab for recurrent high-grade glioma. J Neurooncol. 2012;107(1):133–138. doi:10.1007/s11060-011-0717-z.
   PubMed Web of Science ®Google Scholar
• Friday BB, Anderson SK, Buckner J, et al. Phase II trial of vorinostat in combination with bortezomib in recurrent glioblastoma: a north central cancer treatment group study. Neuro Oncol. 2012;14(2):215–221. doi:10.1093/neuonc/nor198.
   PubMed Web of Science ®Google Scholar
• Wu G, Broniscer A, McEachron TA, et al. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet. 2012;44(3):251–253. doi:10.1038/ng.1102.
   PubMed Web of Science ®Google Scholar
• Schwartzentruber J, Korshunov A, Liu XY, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012;482(7384):226–231. doi:10.1038/nature10833.
   PubMed Web of Science ®Google Scholar
• Wu G, Diaz AK, Paugh BS, et al. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet. 2014;46(5):444–450. doi:10.1038/ng.2938.
   PubMed Web of Science ®Google Scholar
• Lewis PW, Allis CD. Poisoning the “histone code” in pediatric gliomagenesis. Cell Cycle. 2013;12(20):3241–3242. doi:10.4161/cc.26356.
   PubMed Web of Science ®Google Scholar
• Lewis PW, Muller MM, Koletsky MS, et al. Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science. 2013;340(6134):857–861. doi:10.1126/science.1232245.
   PubMed Web of Science ®Google Scholar
• Grasso CS, Tang Y, Truffaux N, et al. Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat Med. 2015;21(7):827. doi:10.1038/nm0715-827a.
   PubMed Web of Science ®Google Scholar
• Hashizume R, Andor N, Ihara Y, et al. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat Med. 2014;20(12):1394–1396. doi:10.1038/nm.3716.
   PubMed Web of Science ®Google Scholar
• Bagcchi S. Panobinostat active against diffuse intrinsic pontine glioma. Lancet Oncol. 2015;16(6):e267. doi:10.1016/S1470-2045(15)70230-5.
   Google Scholar
• Rk Rl L, Reardon DA, Paleologos N, et al. Long-term follow-up of act III: a phase II trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma. Neuro Oncol. 2011;13:34–34.
   Web of Science ®Google Scholar
• Shrimali RK, Yu Z, Theoret MR, et al. Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res. 2010;70(15):6171–6180. doi:10.1158/0008-5472.CAN-10-0153.
   PubMed Web of Science ®Google Scholar
• Li G, Mitra SS, Monje M, et al. Expression of epidermal growth factor variant III (EGFRvIII) in pediatric diffuse intrinsic pontine gliomas. J Neurooncol. 2012;108(3):395–402. doi:10.1007/s11060-012-0842-3.
   PubMed Web of Science ®Google Scholar
• Schumacher T, Bunse L, Pusch S, et al. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature. 2014;512(7514):324–327. doi:10.1038/nature13387.
   PubMed Web of Science ®Google Scholar
• Ampie L, Choy W, Lamano JB, et al. Heat shock protein vaccines against glioblastoma: from bench to bedside. J Neurooncol. 2015;123(3):441–448. doi:10.1007/s11060-015-1837-7.
   PubMed Web of Science ®Google Scholar
• Phuphanich SWC, Rudnick J. Long-term remission over 5 years in patients with newly diagnosed glioblastoma (GBM) treated with ICT-107 vaccine: a follow-up study. Neuro Oncol. 2013;15(suppl 3):iii68–iii74. Abstract#: IT-015 2013
   Google Scholar
• Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 2012;12(4):265–277. doi:10.1038/nrc3258.
   PubMed Web of Science ®Google Scholar
• Liau LM, Prins RM, Kiertscher SM, et al. Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res. 2005;11(15):5515–5525. doi:10.1158/1078-0432.CCR-05-0464.
   PubMed Web of Science ®Google Scholar
• Yu JS, Liu G, Ying H, et al. Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res. 2004;64(14):4973–4979. doi:10.1158/0008-5472.CAN-03-3505.
   PubMed Web of Science ®Google Scholar
• Mitchell DA, Batich KA, Gunn MD, et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 2015;519(7543):366–369. doi:10.1038/nature14320.
   PubMed Web of Science ®Google Scholar
• Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337–341. doi:10.1038/nature14432.
   PubMed Web of Science ®Google Scholar
• Preusser M, Lim M, Hafler DA, et al. Prospects of immune checkpoint modulators in the treatment of glioblastoma. Nat Rev Neurol. 2015;11(9):504–514. doi:10.1038/nrneurol.2015.139.
   PubMed Web of Science ®Google Scholar
• Taube JM, Klein A, Brahmer JR, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20(19):5064–5074. doi:10.1158/1078-0432.CCR-13-3271.
   PubMed Web of Science ®Google Scholar
• Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563–567. doi:10.1038/nature14011.
   PubMed Web of Science ®Google Scholar
• Fecci PE, Ochiai H, Mitchell DA, et al. Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function. Clin Cancer Res. 2007;13(7):2158–2167. doi:10.1158/1078-0432.CCR-06-2070.
   PubMed Web of Science ®Google Scholar
• Kjaergaard J, Tanaka J, Kim JA, et al. Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. Cancer Res. 2000;60(19):5514–5521.
   PubMed Web of Science ®Google Scholar
• Zeng J, See AP, Phallen J, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013;86(2):343–349. doi:10.1016/j.ijrobp.2012.12.025.
   PubMed Web of Science ®Google Scholar
• Weber JS, Yang JC, Atkins MB, et al. Toxicities of immunotherapy for the practitioner. J Clin Oncol. 2015;33(18):2092–2099. doi:10.1200/JCO.2014.60.0379.
   PubMed Web of Science ®Google Scholar
• Okada H, Weller M, Huang R, et al. Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. Lancet Oncol. 2015;16(15):e534–e542. doi:10.1016/S1470-2045(15)00088-1.
   PubMedGoogle Scholar
• Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–2520. doi:10.1056/NEJMoa1500596.
   PubMed Web of Science ®Google Scholar
• Bouffet E, Larouche V, Campbell BB, et al. Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol. 2016. DOI:10.1200/JCO.2016.66.6552.
   PubMed Web of Science ®Google Scholar
• Wollmann G, Ozduman K. van den Pol AN. Oncolytic virus therapy for glioblastoma multiforme: concepts and candidates. Cancer J. 2012;18(1):69–81. doi:10.1097/PPO.0b013e31824671c9.
   PubMed Web of Science ®Google Scholar
• Russell SJ, Peng KW, Bell JC. Oncolytic virotherapy. Nat Biotechnol. 2012;30(7):658–670. doi:10.1038/nbt.2287.
   PubMed Web of Science ®Google Scholar
• Bischoff JR, Kirn DH, Williams A, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science. 1996;274(5286):373–376.
   PubMed Web of Science ®Google Scholar
• Harada N, Maniwa Y, Yoshimura M, et al. E1B-deleted adenovirus replicates in p53-deficient lung cancer cells due to the absence of apoptosis. Oncol Rep. 2005;14(5):1155–1163.
   PubMed Web of Science ®Google Scholar
• Fueyo J, Gomez-Manzano C, Alemany R, et al. A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene. 2000;19(1):2–12. doi:10.1038/sj.onc.1203251.
   PubMed Web of Science ®Google Scholar
• Markert JM, Liechty PG, Wang W, et al. Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. Mol Ther. 2009;17(1):199–207. doi:10.1038/mt.2008.228.
   PubMed Web of Science ®Google Scholar
• Dobrikova EY, Broadt T, Poiley-Nelson J, et al. Recombinant oncolytic poliovirus eliminates glioma in vivo without genetic adaptation to a pathogenic phenotype. Mol Ther. 2008;16(11):1865–1872. doi:10.1038/mt.2008.184.
   PubMed Web of Science ®Google Scholar
• Zamarin D, Holmgaard RB, Subudhi SK, et al. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med. 2014;6(226):226ra32. doi:10.1126/scitranslmed.3008095.
   PubMed Web of Science ®Google Scholar
• Engeland CE, Grossardt C, Veinalde R, et al. CTLA-4 and PD-L1 checkpoint blockade enhances oncolytic measles virus therapy. Mol Ther. 2014;22(11):1949–1959. doi:10.1038/mt.2014.160.
   PubMed Web of Science ®Google Scholar