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Abstract

The blood-brain barrier is critically important for the treatment of both primary and metastatic cancers of the central nervous system (CNS). Clinical outcomes for patients with primary CNS tumors are poor and have not significantly improved in decades. As treatments for patients with extracranial solid tumors improve, the incidence of CNS metastases is on the rise due to suboptimal CNS exposure of otherwise systemically active agents. Despite state-of-the art surgical care and increasingly precise radiation therapy, clinical progress is limited by the ability to deliver an effective dose of a therapeutic agent to all cancerous cells. Given the tremendous heterogeneity of CNS cancers, both across cancer subtypes andwithin a single tumor, and the range of diverse therapies under investigation, a nuanced examination of CNS drug exposure is needed. With a shared goal, common vocabulary, and interdisciplinary collaboration, the field is poised for renewed progress in the treatment of CNS cancers.

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2023-04-11
2024-12-03
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Literature Cited

  1. Abbott NJ, Friedman A. 2012. Overview and introduction: the blood-brain barrier in health and disease. Epilepsia 53:61–6
    [Google Scholar]
  2. Abbott NJ, Rönnbäck L, Hansson E. 2006. Astrocyte–endothelial interactions at the blood–brain barrier. Nat. Rev. Neurosci. 7:41–53
    [Google Scholar]
  3. Achrol AS, Rennert RC, Anders C, Soffietti R, Ahluwalia MS et al. 2019. Brain metastases. Nat. Rev. Dis. Primers. 5:5
    [Google Scholar]
  4. Ahmed N, Brawley V, Hegde M, Bielamowicz K, Kalra M et al. 2017. HER2-specific chimeric antigen receptor-modified virus-specific T cells for progressive glioblastoma: a phase 1 dose-escalation trial. JAMA Oncol 3:81094–101
    [Google Scholar]
  5. Aichler M, Walch A. 2015. MALDI Imaging mass spectrometry: current frontiers and perspectives in pathology research and practice. Lab. Investig. 95:4422–31
    [Google Scholar]
  6. Akhavan D, Alizadeh D, Wang D, Weist MR, Shepphird JK, Brown CE. 2019. CAR T cells for brain tumors: lessons learned and road ahead. Immunol. Rev. 290:60–84
    [Google Scholar]
  7. Arami H, Patel CB, Madsen SJ, Dickinson PJ, Davis RM et al. 2019. Nanomedicine for spontaneous brain tumors: a companion clinical trial. ACS Nano 13:32858–69
    [Google Scholar]
  8. Arnold M, Rutherford MJ, Bardot A, Ferlay J, Andersson TM-L et al. 2019. Progress in cancer survival, mortality, and incidence in seven high-income countries 1995–2014 (ICBP SURVMARK-2): a population-based study. Lancet Oncol 20:111493–505
    [Google Scholar]
  9. Arvanitis CD, Ferraro GB, Jain RK. 2020. The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat. Rev. Cancer 20:26–41
    [Google Scholar]
  10. Arvanitis CD, Livingstone MS, Vykhodtseva N, McDannold N. 2012. Controlled ultrasound-induced blood-brain barrier disruption using passive acoustic emissions monitoring. PLOS ONE 7:9e45783
    [Google Scholar]
  11. Aur RJ, Simone JV, Hustu HO, Verzosa MS. 1972. A comparative study of central nervous system irradiation and intensive chemotherapy early in remission of childhood acute lymphocytic leukemia. Cancer 29:2381–91
    [Google Scholar]
  12. Azhdarinia A, Ghosh P, Ghosh S, Wilganowski N, Sevick-Muraca EM. 2012. Dual-labeling strategies for nuclear and fluorescence molecular imaging: a review and analysis. Mol. Imaging Biol. 14:3261–76
    [Google Scholar]
  13. Bake S, Friedman JA, Sohrabji F. 2009. Reproductive age-related changes in the blood brain barrier: expression of IgG and tight junction proteins. Microvasc. Res. 78:3413–24
    [Google Scholar]
  14. Banks WA. 2016. From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nat. Rev. Drug. Discov. 15:4275–92
    [Google Scholar]
  15. Basu SS, Agar NYR. 2021. Bringing matrix-assisted laser desorption/ionization mass spectrometry imaging to the clinics. Clin. Lab. Med. 41:2309–24
    [Google Scholar]
  16. Basu SS, Regan MS, Randall EC, Abdelmoula WM, Clark AR et al. 2019. Rapid MALDI mass spectrometry imaging for surgical pathology. NPJ Precis. Oncol. 3:17
    [Google Scholar]
  17. Basu SS, Stopka SA, Abdelmoula WM, Randall EC, Gimenez-Cassina Lopez B et al. 2021. Interim clinical trial analysis of intraoperative mass spectrometry for breast cancer surgery. NPJ Breast Cancer 7:116
    [Google Scholar]
  18. Bendell JC, Domchek SM, Burstein HJ, Harris L, Younger J et al. 2003. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:122972–77
    [Google Scholar]
  19. Bernier L-P, Brunner C, Cottarelli A, Balbi M. 2021. Location matters: navigating regional heterogeneity of the neurovascular unit. Front. Cell. Neurosci. 15:696540
    [Google Scholar]
  20. Bi WL, Nayak L, Meredith DM, Driver J, Du Z et al. 2022. Activity of PD-1 blockade with nivolumab among patients with recurrent atypical/anaplastic meningioma: phase II trial results. Neuro-Oncology 24:1101–13
    [Google Scholar]
  21. Bidros DS, Liu JK, Vogelbaum MA. 2010. Future of convection-enhanced delivery in the treatment of brain tumors. Future Oncol 6:1117–25
    [Google Scholar]
  22. Bobo RH, Laske DW, Akbasak A, Morrison PF, Dedrick RL, Oldfield EH. 1994. Convection-enhanced delivery of macromolecules in the brain. PNAS 91:62076–80
    [Google Scholar]
  23. Boudreau CE, Najem H, Ott M, Horbinski C, Fang D et al. 2021. Intratumoral delivery of STING agonist results in clinical responses in canine glioblastoma. Clin. Cancer Res. 27:205528–35
    [Google Scholar]
  24. Brastianos PK, Kim AE, Giobbie-Hurder A, Lee EQ, Wang N et al. 2022. Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas. Nat. Commun. 13:1325
    [Google Scholar]
  25. Brown CE, Badie B, Barish ME, Weng L, Ostberg JR et al. 2015. Bioactivity and safety of IL13Rα2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin. Cancer Res. 21:184062–72
    [Google Scholar]
  26. Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ et al. 2016. Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol 2:111460–69
    [Google Scholar]
  27. Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B et al. 2006. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J. Clin. Oncol. 24:182707–14
    [Google Scholar]
  28. Carlson BL, Pokorny JL, Schroeder MA, Sarkaria JN. 2011. Establishment, maintenance and in vitro and in vivo applications of primary human glioblastoma multiforme (GBM) xenograft models for translational biology studies and drug discovery. Curr. Protoc. Pharmacol. 52:14.16.1–14.16.23
    [Google Scholar]
  29. Carmeliet P, Jain RK. 2011. Molecular mechanisms and clinical applications of angiogenesis. Nature 473:7347298–307
    [Google Scholar]
  30. Chotsampancharoen T, Sripornsawan P, Wongchanchailert M. 2016. Two fatal cases of accidental intrathecal vincristine administration: learning from death events. Chemotherapy 61:2108–10
    [Google Scholar]
  31. Chuntova P, Chow F, Watchmaker PB, Galvez M, Heimberger AB et al. 2021. Unique challenges for glioblastoma immunotherapy-discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank. Neuro-Oncology 23:3356–75
    [Google Scholar]
  32. Clement JM, Holle LM. 2017. Safe administration of intracerebral spinal fluid chemotherapy: time for guidelines. J. Oncol. Pract. 13:11713–18
    [Google Scholar]
  33. Cloughesy TF, Landolfi J, Vogelbaum MA, Ostertag D, Elder JB et al. 2018. Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC. Neuro-Oncology 20:101383–92
    [Google Scholar]
  34. Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH et al. 2019. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat. Med. 25:3477–86
    [Google Scholar]
  35. Daneman R, Prat A. 2015. The blood-brain barrier. Cold Spring Harb. Perspect. Biol. 7:1a020412
    [Google Scholar]
  36. Dani N, Herbst RH, McCabe C, Green GS, Kaiser K et al. 2021. A cellular and spatial map of the choroid plexus across brain ventricles and ages. Cell 184:113056–74.e21
    [Google Scholar]
  37. Darmanis S, Sloan SA, Croote D, Mignardi M, Chernikova S et al. 2017. Single-cell RNA-seq analysis of infiltrating neoplastic cells at the migrating front of human glioblastoma. Cell Rep 21:51399–410
    [Google Scholar]
  38. de Lange EC. 2013. The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects. Fluids Barriers CNS 10:112
    [Google Scholar]
  39. DeNunzio NJ, Yock TI. 2020. Modern radiotherapy for pediatric brain tumors. Cancers 12:6E1533
    [Google Scholar]
  40. Desjardins A, Gromeier M, Herndon JE, Beaubier N, Bolognesi DP et al. 2018. Recurrent glioblastoma treated with recombinant poliovirus. N. Engl. J. Med. 379:2150–61
    [Google Scholar]
  41. Di L, Rong H, Feng B. 2013. Demystifying brain penetration in central nervous system drug discovery. J. Med. Chem. 56:12–12
    [Google Scholar]
  42. Dunkel IJ, Boyett JM, Yates A, Rosenblum M, Garvin JH et al. 1998. High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children's Cancer Group. J. Clin. Oncol. 16:1222–28
    [Google Scholar]
  43. Dyer C. 2001. Doctors suspended after injecting wrong drug into spine. BMJ 322:7281257
    [Google Scholar]
  44. El-Mashtoly SF, Petersen D, Yosef HK, Mosig A, Reinacher-Schick A et al. 2014. Label-free imaging of drug distribution and metabolism in colon cancer cells by Raman microscopy. Analyst 139:51155–61
    [Google Scholar]
  45. FDA (US Food Drug Admin.) 2021. IND applications for clinical investigations: pharmacology and toxicology (PT) information Web Resour., U.S. Food Drug Admin. Silver Spring, MD:
    [Google Scholar]
  46. Feng B, Doran AC, Di L, West MA, Osgood SM et al. 2018. Prediction of human brain penetration of P-glycoprotein and breast cancer resistance protein substrates using in vitro transporter studies and animal models. J. Pharm. Sci. 107:82225–35
    [Google Scholar]
  47. Filbin MG, Tirosh I, Hovestadt V, Shaw ML, Escalante LE et al. 2018. Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq. Science 360:6386331–35
    [Google Scholar]
  48. Flores C, Dunn G, Fecci P, Lim M, Mitchell D, Reardon DA. 2022. Is there a role for immunotherapy in central nervous system cancers?. Hematol. Oncol. Clin. N. Am. 36:1237–52
    [Google Scholar]
  49. Freedman RA, Gelman RS, Agar NYR, Santagata S, Randall EC et al. 2020. Pre- and postoperative neratinib for HER2-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium 022. Clin. Breast Cancer 20:2145–51.e2
    [Google Scholar]
  50. Friedman GK, Johnston JM, Bag AK, Bernstock JD, Li R et al. 2021. Oncolytic HSV-1 G207 immunovirotherapy for pediatric high-grade gliomas. N. Engl. J. Med. 384:171613–22
    [Google Scholar]
  51. Frisk G, Svensson T, Bäcklund LM, Lidbrink E, Blomqvist P, Smedby KE. 2012. Incidence and time trends of brain metastases admissions among breast cancer patients in Sweden. Br. J. Cancer 106:111850–53
    [Google Scholar]
  52. Furtado A, Mineiro R, Duarte AC, Gonçalves I, Santos CR, Quintela T. 2022. The daily expression of ABCC4 at the BCSFB affects the transport of its substrate methotrexate. Int. J. Mol. Sci. 23:52443
    [Google Scholar]
  53. Gajjar A, Robinson GW, Smith KS, Lin T, Merchant TE et al. 2021. Outcomes by clinical and molecular features in children with medulloblastoma treated with risk-adapted therapy: results of an international phase III trial (SJMB03). J. Clin. Oncol. 39:7822–35
    [Google Scholar]
  54. Garcia FJ, Sun N, Lee H, Godlewski B, Mathys H et al. 2022. Single-cell dissection of the human brain vasculature. Nature 603:7903893–99
    [Google Scholar]
  55. Gerstner ER, Emblem KE, Chang K, Vakulenko-Lagun B, Yen YF et al. 2020. Bevacizumab reduces permeability and concurrent temozolomide delivery in a subset of patients with recurrent glioblastoma. Clin. Cancer Res. 26:1206–12
    [Google Scholar]
  56. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT et al. 2014. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N. Engl. J. Med. 370:8699–708
    [Google Scholar]
  57. Goff SL, Morgan RA, Yang JC, Sherry RM, Robbins PF et al. 2019. Pilot trial of adoptive transfer of chimeric antigen receptor-transduced T cells targeting EGFRvIII in patients with glioblastoma. J. Immunother. 42:4126–35
    [Google Scholar]
  58. Gojo J, Englinger B, Jiang L, Hübner JM, Shaw ML et al. 2020. Single-cell RNA-seq reveals cellular hierarchies and impaired developmental trajectories in pediatric ependymoma. Cancer Cell 38:144–59.e9
    [Google Scholar]
  59. Goldberg SB, Schalper KA, Gettinger SN, Mahajan A, Herbst RS et al. 2020. Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. Lancet Oncol 21:5655–63
    [Google Scholar]
  60. Groothuis DR, Warkne PC, Molnar P, Lapin GD, Mikhael MA. 1990. Effect of hyperosmotic blood-brain barrier disruption on transcapillary transport in canine brain tumors. J. Neurosurg. 72:3441–49
    [Google Scholar]
  61. Hajal C, Le Roi B, Kamm RD, Maoz BM 2021. Biology and models of the blood-brain barrier. Annu. Rev. Biomed. Eng. 23:359–84
    [Google Scholar]
  62. Hase Y, Ding R, Harrison G, Hawthorne E, King A et al. 2019. White matter capillaries in vascular and neurodegenerative dementias. Acta Neuropathol. Commun. 7:16
    [Google Scholar]
  63. Hawkins BT, Davis TP. 2005. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev. 57:2173–85
    [Google Scholar]
  64. Heideman RL, Cole DE, Balis F, Sato J, Reaman GH et al. 1989. Phase I and pharmacokinetic evaluation of thiotepa in the cerebrospinal fluid and plasma of pediatric patients: evidence for dose-dependent plasma clearance of thiotepa. Cancer Res 49:3736–41
    [Google Scholar]
  65. Heideman RL, Packer RJ, Reaman GH, Allen JC, Lange B et al. 1993. A phase II evaluation of thiotepa in pediatric central nervous system malignancies. Cancer 72:271–75
    [Google Scholar]
  66. Herting CJ, Chen Z, Maximov V, Duffy A, Szulzewsky F et al. 2019. Tumour-associated macrophage-derived interleukin-1 mediates glioblastoma-associated cerebral oedema. Brain 142:123834–51
    [Google Scholar]
  67. Hidalgo M, Amant F, Biankin AV, Budinská E, Byrne AT et al. 2014. Patient-derived xenograft models: an emerging platform for translational cancer research. Cancer Discov 4:9998–1013
    [Google Scholar]
  68. Hilf N, Kuttruff-Coqui S, Frenzel K, Bukur V, Stevanović S et al. 2019. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature 565:7738240–45
    [Google Scholar]
  69. Hoffe B, Holahan MR. 2019. The use of pigs as a translational model for studying neurodegenerative diseases. Front. Physiol. 10:838
    [Google Scholar]
  70. Hoshi Y, Uchida Y, Tachikawa M, Inoue T, Ohtsuki S, Terasaki T. 2013. Quantitative atlas of blood-brain barrier transporters, receptors, and tight junction proteins in rats and common marmoset. J. Pharm. Sci. 102:93343–55
    [Google Scholar]
  71. Hovestadt V, Smith KS, Bihannic L, Filbin MG, Shaw ML et al. 2019. Resolving medulloblastoma cellular architecture by single-cell genomics. Nature 572:776774–79
    [Google Scholar]
  72. Iorgulescu JB, Gokhale PC, Speranza MC, Eschle BK, Poitras MJ et al. 2021. Concurrent dexamethasone limits the clinical benefit of immune checkpoint blockade in glioblastoma. Clin. Cancer Res. 27:1276–87
    [Google Scholar]
  73. Jamieson D, Griffin MJ, Sludden J, Drew Y, Cresti N et al. 2016. A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours. Eur. J. Cancer. 68:1–10
    [Google Scholar]
  74. Johanson CE, Stopa EG, McMillan PN. 2011. The blood-cerebrospinal fluid barrier: structure and functional significance. Methods Mol. Biol. 686:101–31
    [Google Scholar]
  75. Joseph JV, Blaavand MS, Daubon T, Kruyt FA, Thomsen MK. 2021. Three-dimensional culture models to study glioblastoma—current trends and future perspectives. Curr. Opin. Pharmacol. 61:91–97
    [Google Scholar]
  76. Jucaite A, Stenkrona P, Cselényi Z, De Vita S, Buil-Bruna N et al. 2021. Brain exposure of the ATM inhibitor AZD1390 in humans-a positron emission tomography study. Neuro-Oncology 23:4687–96
    [Google Scholar]
  77. Kersten K, de Visser KE, van Miltenburg MH, Jonkers J. 2017. Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol. Med. 9:2137–53
    [Google Scholar]
  78. Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND et al. 2019. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 565:7738234–39
    [Google Scholar]
  79. Kövesdi E, Szabó-Meleg E, Abrahám IM. 2020. The role of estradiol in traumatic brain injury: mechanism and treatment potential. Int. J. Mol. Sci. 22:E11
    [Google Scholar]
  80. Kuczynski EA, Vermeulen PB, Pezzella F, Kerbel RS, Reynolds AR. 2019. Vessel co-option in cancer. Nat. Rev. Clin. Oncol. 16:8469–93
    [Google Scholar]
  81. Kulkarni JA, Witzigmann D, Thomson SB, Chen S, Leavitt BR et al. 2021. The current landscape of nucleic acid therapeutics. Nat. Nanotechnol. 16:6630–43
    [Google Scholar]
  82. Kumar K, Butowski N, Aghi M, Bankiewicz K, Bringas J et al. 2019. SCIDOT-02. A phase I study of convection-enhanced delivery of liposomal-irinotecan (onivyde) using real-time imaging with gadolinium in patients with recurrent high grade gliomas: results thus far. Neuro-Oncology 21:Suppl. 6 vi272 (Abstr.)
    [Google Scholar]
  83. Kwong Y-L, Yeung DYM, Chan JCW. 2009. Intrathecal chemotherapy for hematologic malignancies: drugs and toxicities. Ann. Hematol. 88:3193–201
    [Google Scholar]
  84. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W et al. 2001. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J. Neurosurg. 95:2190–98
    [Google Scholar]
  85. Lamba N, Wen PY, Aizer AA. 2021. Epidemiology of brain metastases and leptomeningeal disease. Neuro-Oncology 23:91447–56
    [Google Scholar]
  86. Lang FF, Conrad C, Gomez-Manzano C, Yung WKA, Sawaya R et al. 2018. Phase I study of DNX-2401 (Delta-24-RGD) oncolytic adenovirus: replication and immunotherapeutic effects in recurrent malignant glioma. J. Clin. Oncol. 36:141419–27
    [Google Scholar]
  87. Langen UH, Ayloo S, Gu C. 2019. Development and cell biology of the blood-brain barrier. Annu. Rev. Cell Dev. Biol. 35:591–613
    [Google Scholar]
  88. Letchuman V, Ampie L, Shah AH, Brown DA, Heiss JD, Chittiboina P. 2022. Syngeneic murine glioblastoma models: reactionary immune changes and immunotherapy intervention outcomes. Neurosurg. Focus 52:2E5
    [Google Scholar]
  89. Leyland-Jones B. 2009. Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases. J. Clin. Oncol. 27:315278–86
    [Google Scholar]
  90. Liddelow SA. 2015. Development of the choroid plexus and blood-CSF barrier. Front. Neurosci. 9:32
    [Google Scholar]
  91. Liechty WB, Kryscio DR, Slaughter BV, Peppas NA. 2010. Polymers for drug delivery systems. Annu. Rev. Chem. Biomol. Eng. 1:149–73
    [Google Scholar]
  92. Ling J, Weitman SD, Miller MA, Moore RV, Bovik AC. 2002. Direct Raman imaging techniques for study of the subcellular distribution of a drug. Appl. Opt. 41:286006–17
    [Google Scholar]
  93. Liu B, Goodwin JE. 2020. The effect of glucocorticoids on angiogenesis in the treatment of solid tumors. J. Cell Signal. 1:342–49
    [Google Scholar]
  94. Liu X, Ide JL, Norton I, Marchionni MA, Ebling MC et al. 2013. Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging. Sci. Rep 3:2859
    [Google Scholar]
  95. Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA et al. 2012. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol 13:111087–95
    [Google Scholar]
  96. Lopez BGC, Kohale IN, Du Z, Korsunsky I, Abdelmoula WM et al. 2022. Multimodal platform for assessing drug distribution and response in clinical trials. Neuro-Oncology 24:164–77
    [Google Scholar]
  97. Loryan I, Sinha V, Mackie C, Van Peer A, Drinkenburg WH et al. 2015. Molecular properties determining unbound intracellular and extracellular brain exposure of CNS drug candidates. Mol. Pharm. 12:2520–32
    [Google Scholar]
  98. Löscher W, Potschka H. 2005. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx 2:86–98
    [Google Scholar]
  99. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D et al. 2016. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:6803–20
    [Google Scholar]
  100. Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA et al. 2021. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-Oncology 23:81231–51
    [Google Scholar]
  101. MacDiarmid JA, Langova V, Bailey D, Pattison ST, Pattison SL et al. 2016. Targeted doxorubicin delivery to brain tumors via minicells: proof of principle using dogs with spontaneously occurring tumors as a model. PLOS ONE 11:4e0151832
    [Google Scholar]
  102. Mainprize T, Lipsman N, Huang Y, Meng Y, Bethune A et al. 2019. Blood-brain barrier opening in primary brain tumors with non-invasive MR-guided focused ultrasound: a clinical safety and feasibility study. Sci. Rep. 9:321
    [Google Scholar]
  103. Majzner RG, Ramakrishna S, Yeom KW, Patel S, Chinnasamy H et al. 2022. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature 603:7903934–41
    [Google Scholar]
  104. Martínez Bernal G, Mezquita L, Auclin E, Ferrara R, Planchard D et al. 2017. Baseline corticosteroids (CS) could be associated with absence of benefit to immune checkpoint inhibitors (ICI) in advanced non-small cell lung cancer (NSCLC) patients. Ann. Oncol. 28:v472 Abstr. )
    [Google Scholar]
  105. Matthews PM, Rabiner EA, Passchier J, Gunn RN. 2012. Positron emission tomography molecular imaging for drug development. Br. J. Clin. Pharmacol. 73:2175–86
    [Google Scholar]
  106. Miller KD, Ostrom QT, Kruchko C, Patil N, Tihan T et al. 2021. Brain and other central nervous system tumor statistics, 2021. CA Cancer J. Clin. 71:5381–406
    [Google Scholar]
  107. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. 2021. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug. Discov. 20:2101–24
    [Google Scholar]
  108. Mittapalli RK, Vaidhyanathan S, Dudek AZ, Elmquist WF. 2013. Mechanisms limiting distribution of the threonine-protein kinase B-RaF(V600E) inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases. J. Pharmacol. Exp. Ther. 344:3655–64
    [Google Scholar]
  109. Morris ME, Rodriguez-Cruz V, Felmlee MA. 2017. SLC and ABC transporters: expression, localization, and species differences at the blood-brain and the blood-cerebrospinal fluid barriers. AAPS J 19:51317–31
    [Google Scholar]
  110. Motl S, Zhuang Y, Waters CM, Stewart CF. 2006. Pharmacokinetic considerations in the treatment of CNS tumours. Clin. Pharmacokinet. 45:9871–903
    [Google Scholar]
  111. Muldoon LL, Soussain C, Jahnke K, Johanson C, Siegal T et al. 2007. Chemotherapy delivery issues in central nervous system malignancy: a reality check. J. Clin. Oncol. 25:162295–305
    [Google Scholar]
  112. Narita Y, Arakawa Y, Yamasaki F, Nishikawa R, Aoki T et al. 2019. A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma. Neuro-Oncology 21:3348–59
    [Google Scholar]
  113. Nayak L, Molinaro AM, Peters K, Clarke JL, Jordan JT et al. 2021. Randomized phase II and biomarker study of pembrolizumab plus bevacizumab versus pembrolizumab alone for patients with recurrent glioblastoma. Clin. Cancer Res. 27:41048–57
    [Google Scholar]
  114. Nayar G, Ejikeme T, Chongsathidkiet P, Elsamadicy AA, Blackwell KL et al. 2017. Leptomeningeal disease: current diagnostic and therapeutic strategies. Oncotarget 8:4273312–28
    [Google Scholar]
  115. Neftel C, Laffy J, Filbin MG, Hara T, Shore ME et al. 2019. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell 178:4835–49.e21
    [Google Scholar]
  116. Ng TSC, Hu H, Kronister S, Lee C, Li R et al. 2022. Overcoming differential tumor penetration of BRAF inhibitors using computationally guided combination therapy. Sci. Adv. 8:17eabl6339
    [Google Scholar]
  117. Nicholson C. 2001. Diffusion and related transport mechanisms in brain tissue. Rep. Prog. Phys. 64:7815–84
    [Google Scholar]
  118. Nyúl-Tóth Á, Suciu M, Molnár J, Fazakas C, Haskó J et al. 2016. Differences in the molecular structure of the blood-brain barrier in the cerebral cortex and white matter: an in silico, in vitro, and ex vivo study. Am. J. Physiol. Heart Circ. Physiol. 310:11H1702–14
    [Google Scholar]
  119. O'Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K et al. 2017. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci. Transl. Med. 9:399eaaa0984
    [Google Scholar]
  120. Obermeier B, Daneman R, Ransohoff RM. 2013. Development, maintenance and disruption of the blood-brain barrier. Nat. Med. 19:121584–96
    [Google Scholar]
  121. Oh T, Fakurnejad S, Sayegh ET, Clark AJ, Ivan ME et al. 2014. Immunocompetent murine models for the study of glioblastoma immunotherapy. J. Transl. Med. 12:107
    [Google Scholar]
  122. Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J et al. 2018. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro-Oncology 20:5674–86
    [Google Scholar]
  123. Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. 2021. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2014–2018. Neuro-Oncology 23:Suppl. 3iii1–105 ( Abstr. )
    [Google Scholar]
  124. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y et al. 1990. A randomized trial of surgery in the treatment of single metastases to the brain. N. Engl. J. Med. 322:8494–500
    [Google Scholar]
  125. Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS et al. 2017. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N. Engl. J. Med. 377:9829–38
    [Google Scholar]
  126. Phoenix TN, Patmore DM, Boop S, Boulos N, Jacus MO et al. 2016. Medulloblastoma genotype dictates blood brain barrier phenotype. Cancer Cell 29:4508–22
    [Google Scholar]
  127. Pike A, Williamson B, Harlfinger S, Martin S, McGinnity DF. 2020. Optimising proteolysis-targeting chimeras (PROTACs) for oral drug delivery: a drug metabolism and pharmacokinetics perspective. Drug Discov. Today 25:101793–800
    [Google Scholar]
  128. Platten M, Schilling D, Bunse L, Wick A, Bunse T et al. 2018. OS6.4 NOA-16: A first-in-man multicenter phase I clinical trial of the German Neurooncology Working Group evaluating a mutation-specific peptide vaccine targeting IDH1R132H in patients with newly diagnosed malignant astrocytomas. Neuro-Oncology 20:Suppl. 3iii226–27 ( Abstr. )
    [Google Scholar]
  129. Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M et al. 2020. Effect of nivolumab versus bevacizumab in patients with recurrent glioblastoma: the CheckMate 143 phase 3 randomized clinical trial. JAMA Oncol 6:71003–10
    [Google Scholar]
  130. Redzic ZB, Preston JE, Duncan JA, Chodobski A, Szmydynger-Chodobska J. 2005. The choroid plexus-cerebrospinal fluid system: from development to aging. Curr. Top. Dev. Biol. 71:1–52
    [Google Scholar]
  131. Ribatti D, Pezzella F. 2022. Vascular co-option and other alternative modalities of growth of tumor vasculature in glioblastoma. Front. Oncol. 12:874554
    [Google Scholar]
  132. Richards S, Pui C-H, Gayon P, CALLCG (Child. Acute Lymphobl. Leuk. Collab. Group) 2013. Systematic review and meta-analysis of randomized trials of central nervous system directed therapy for childhood acute lymphoblastic leukemia. Pediatr. Blood Cancer 60:2185–95
    [Google Scholar]
  133. Robertson FL, Marqués-Torrejón M-A, Morrison GM, Pollard SM. 2019. Experimental models and tools to tackle glioblastoma. Dis. Models Mech. 12:9dmm040386
    [Google Scholar]
  134. Sandoval KE, Witt KA. 2011. Age and 17β-estradiol effects on blood-brain barrier tight junction and estrogen receptor proteins in ovariectomized rats. Microvasc. Res. 81:2198–205
    [Google Scholar]
  135. Schalper KA, Rodriguez-Ruiz ME, Diez-Valle R, López-Janeiro A, Porciuncula A et al. 2019. Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma. Nat. Med. 25:3470–76
    [Google Scholar]
  136. Schlageter KE, Molnar P, Lapin GD, Groothuis DR. 1999. Microvessel organization and structure in experimental brain tumors: microvessel populations with distinctive structural and functional properties. Microvasc. Res. 58:3312–28
    [Google Scholar]
  137. Singh J, Petter RC, Baillie TA, Whitty A. 2011. The resurgence of covalent drugs. Nat. Rev. Drug. Discov. 10:4307–17
    [Google Scholar]
  138. Stelzer KJ. 2013. Epidemiology and prognosis of brain metastases. Surg. Neurol. Int. 4:Suppl. 4S192–202
    [Google Scholar]
  139. Straehla JP, Hajal C, Safford HC, Offeddu GS, Boehnke N et al. 2022. A predictive microfluidic model of human glioblastoma to assess trafficking of blood-brain barrier-penetrant nanoparticles. PNAS 119:23e2118697119
    [Google Scholar]
  140. Sulman EP, Ismaila N, Armstrong TS, Tsien C, Batchelor TT et al. 2017. Radiation therapy for glioblastoma: American Society of Clinical Oncology clinical practice guideline endorsement of the American Society for Radiation Oncology guideline. J. Clin. Oncol. 35:3361–69
    [Google Scholar]
  141. Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS et al. 2018. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N. Engl. J. Med. 379:8722–30
    [Google Scholar]
  142. Tawbi HA, Forsyth PA, Hodi FS, Lao CD, Moschos SJ et al. 2021. Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). Neuro-Oncology 23:111961–73
    [Google Scholar]
  143. Teuwen L-A, De Rooij LPMH, Cuypers A, Rohlenova K, Dumas SJ et al. 2021. Tumor vessel co-option probed by single-cell analysis. Cell Rep 35:11109253
    [Google Scholar]
  144. Tosi U, Souweidane M. 2020. Convection enhanced delivery for diffuse intrinsic pontine glioma: review of a single institution experience. Pharmaceutics 12:7660
    [Google Scholar]
  145. van Putten EHP, Kleijn A, van Beusechem VW, Noske D, Lamers CHJ et al. 2022. Convection enhanced delivery of the oncolytic adenovirus Delta24-RGD in patients with recurrent GBM: a phase I clinical trial including correlative studies. Clin. Cancer Res. 28:81572–85
    [Google Scholar]
  146. Vogelbaum MA, Brown PD, Messersmith H, Brastianos PK, Burri S et al. 2022. Treatment for brain metastases: ASCO-SNO-ASTRO guideline. J. Clin. Oncol. 40:5492–516
    [Google Scholar]
  147. Vredenburgh JJ, Desjardins A, Herndon JE, Dowell JM, Reardon DA et al. 2007. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin. Cancer Res. 13:41253–59
    [Google Scholar]
  148. Walker WH, Sprowls SA, Bumgarner JR, Liu JA, Meléndez-Fernández OH et al. 2021. Circadian influences on chemotherapy efficacy in a mouse model of brain metastases of breast cancer. Front. Oncol. 11:752331
    [Google Scholar]
  149. Wang N, Bertalan MS, Brastianos PK. 2018. Leptomeningeal metastasis from systemic cancer: review and update on management. Cancer 124:121–35
    [Google Scholar]
  150. Warren KE. 2018. Beyond the blood:brain barrier: the importance of central nervous system (CNS) pharmacokinetics for the treatment of CNS tumors, including diffuse intrinsic pontine glioma. Front. Oncol. 8:239
    [Google Scholar]
  151. Wei X, Meel MH, Breur M, Bugiani M, Hulleman E, Phoenix TN. 2021. Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas. Acta Neuropathol. Commun. 9:142
    [Google Scholar]
  152. Wen PY, Reardon DA, Armstrong TS, Phuphanich S, Aiken RD et al. 2019a. A randomized double-blind placebo-controlled phase II trial of dendritic cell vaccine ICT-107 in newly diagnosed patients with glioblastoma. Clin. Cancer Res. 25:195799–807
    [Google Scholar]
  153. Wen PY, Touat M, Alexander BM, Mellinghoff IK, Ramkissoon S et al. 2019b. Buparlisib in patients with recurrent glioblastoma harboring phosphatidylinositol 3-kinase pathway activation: an open-label, multicenter, multi-arm, phase II trial. J. Clin. Oncol. 37:9741–50
    [Google Scholar]
  154. Winkler EA, Sengillo JD, Sullivan JS, Henkel JS, Appel SH, Zlokovic BV. 2013. Blood-spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis. Acta Neuropathol 125:111–20
    [Google Scholar]
  155. Workman MJ, Svendsen CN. 2020. Recent advances in human iPSC-derived models of the blood-brain barrier. Fluids Barriers CNS 17:30
    [Google Scholar]
  156. Workman P, Aboagye EO, Chung Y-L, Griffiths JR, Hart R et al. 2006. Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies. J. Natl. Cancer Inst. 98:9580–98
    [Google Scholar]
  157. Wüstner D, Solanko LM, Lund FW, Sage D, Schroll HJ, Lomholt MA. 2012. Quantitative fluorescence loss in photobleaching for analysis of protein transport and aggregation. BMC Bioinform 13:296
    [Google Scholar]
  158. Xie Y, He L, Lugano R, Zhang Y, Cao H et al. 2021. Key molecular alterations in endothelial cells in human glioblastoma uncovered through single-cell RNA sequencing. JCI Insight 6:15150861
    [Google Scholar]
  159. Yamanaka R, Homma J, Yajima N, Tsuchiya N, Sano M et al. 2005. Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial. Clin. Cancer Res. 11:114160–67
    [Google Scholar]
  160. Yamazaki Y, Baker DJ, Tachibana M, Liu C-C, van Deursen JM et al. 2016. Vascular cell senescence contributes to blood-brain barrier breakdown. Stroke 47:41068–77
    [Google Scholar]
  161. Zhang SL, Yue Z, Arnold DM, Artiushin G, Sehgal A. 2018. A circadian clock in the blood-brain barrier regulates xenobiotic efflux. Cell 173:130–39.e10
    [Google Scholar]
  162. Zhao J, Chen AX, Gartrell RD, Silverman AM, Aparicio L et al. 2019. Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma. Nat. Med. 25:3462–69
    [Google Scholar]
  163. Zhao L, Ren T, Wang DD. 2012. Clinical pharmacology considerations in biologics development. Acta Pharmacol. Sin. 33:111339–47
    [Google Scholar]
  164. Zhou H, Mehta S, Srivastava SP, Grabinska K, Zhang X et al. 2020. Endothelial cell-glucocorticoid receptor interactions and regulation of Wnt signaling. JCI Insight 5:3e131384
    [Google Scholar]
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