Challenges to curing primary brain tumours.

Brain Neoplasms / therapy Humans

Journal

Nature reviews. Clinical oncology
ISSN: 1759-4782
Titre abrégé: Nat Rev Clin Oncol
Pays: England
ID NLM: 101500077

Informations de publication

Date de publication:
08 2019
Historique:
pubmed: 9 2 2019
medline: 30 11 2019
entrez: 9 2 2019
Statut: ppublish

Résumé

Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properties of neural tissues. In an attempt to encourage progress in our understanding and ability to successfully treat patients with brain tumours, Cancer Research UK convened an international panel of clinicians and laboratory-based scientists to identify challenges that must be overcome if we are to cure all patients with a brain tumour. The seven key challenges summarized in this Position Paper are intended to serve as foci for future research and investment.

Identifiants

DOI: 10.1038/s41571-019-0177-5 PMID: 30733593 PMC: PMC6650350
pubmed: 30733593
doi: 10.1038/s41571-019-0177-5
pii: 10.1038/s41571-019-0177-5
pmc: PMC6650350
mid: NIHMS1035140
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

509-520

Subventions

Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA116659
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 CA999999
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS089272
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA129958
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197718
Pays : United States
Organisme : NINDS NIH HHS
ID : K02 NS047409
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014236
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA096832
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Références

Gilbert, M. R. et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N. Engl. J. Med. 370, 699–708 (2014).
pubmed: 24552317 pmcid: 4201043 doi: 10.1056/NEJMoa1308573
Chinot, O. L. et al. Bevacizumab plus radiotherapy–temozolomide for newly diagnosed glioblastoma. N. Engl. J. Med. 370, 709–722 (2014).
pubmed: 24552318 doi: 10.1056/NEJMoa1308345
Smith, M. A. & Reaman, G. H. Remaining challenges in childhood cancer and newer targeted therapeutics. Pediatr. Clin. North Am. 62, 301–312 (2015).
pubmed: 25435124 doi: 10.1016/j.pcl.2014.09.018
Brinkman, T. M. et al. Long-term neurocognitive functioning and social attainment in adult survivors of pediatric CNS tumors: results from the St Jude Lifetime Cohort Study. J. Clin. Oncol. 34, 1358–1367 (2016).
pubmed: 26834063 pmcid: 4933131 doi: 10.1200/JCO.2015.62.2589
Chemaitilly, W., Armstrong, G. T., Gajjar, A. & Hudson, M. M. Hypothalamic-pituitary axis dysfunction in survivors of childhood CNS tumors: importance of systematic follow-up and early endocrine consultation. J. Clin. Oncol. 34, 4315–4319 (2016).
pubmed: 27998231 doi: 10.1200/JCO.2016.70.1847
Phoenix, T. N. et al. Medulloblastoma genotype dictates blood brain barrier phenotype. Cancer Cell 29, 508–522 (2016).
pubmed: 27050100 pmcid: 4829447 doi: 10.1016/j.ccell.2016.03.002
Gerstner, E. R. & Fine, R. L. Increased permeability of the blood-brain barrier to chemotherapy in metastatic brain tumors: establishing a treatment paradigm. J. Clin. Oncol. 25, 2306–2312 (2007).
pubmed: 17538177 doi: 10.1200/JCO.2006.10.0677
Mackay, A. et al. Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma. Cancer Cell 32, 520–537 (2017).
pubmed: 28966033 pmcid: 5637314 doi: 10.1016/j.ccell.2017.08.017
Quail, D. F. & Joyce, J. A. The microenvironmental landscape of brain tumors. Cancer Cell 31, 326–341 (2017).
pubmed: 28292436 pmcid: 5424263 doi: 10.1016/j.ccell.2017.02.009
Gilbertson, R. J. Mapping cancer origins. Cell 145, 25–29 (2011).
pubmed: 21458665 pmcid: 3077217 doi: 10.1016/j.cell.2011.03.019
Nimmervoll, B. et al. Establishing a preclinical multidisciplinary board for brain tumors. Clin. Cancer Res. 24, 1654–1666 (2018).
pubmed: 29301833 pmcid: 5884708 doi: 10.1158/1078-0432.CCR-17-2168
Northcott, P. A. et al. Medulloblastomics: the end of the beginning. Nat. Rev. Cancer 12, 818–834 (2012).
pubmed: 23175120 pmcid: 3889646 doi: 10.1038/nrc3410
Chow, S. C. Adaptive clinical trial design. Annu. Rev. Med. 65, 405–415 (2014).
pubmed: 24422576 doi: 10.1146/annurev-med-092012-112310
Alexander, B. M. et al. Adaptive global innovative learning environment for glioblastoma: GBM AGILE. Clin. Cancer Res. 24, 737–743 (2018).
pubmed: 28814435 doi: 10.1158/1078-0432.CCR-17-0764
Kriegstein, A. & Alvarez-Buylla, A. The glial nature of embryonic and adult neural stem cells. Annu. Rev. Neurosci. 32, 149–184 (2009).
pubmed: 19555289 pmcid: 3086722 doi: 10.1146/annurev.neuro.051508.135600
Bjornsson, C. S., Apostolopoulou, M., Tian, Y. & Temple, S. It takes a village: constructing the neurogenic niche. Dev. Cell 32, 435–446 (2015).
pubmed: 25710530 pmcid: 4886554 doi: 10.1016/j.devcel.2015.01.010
Singh, S. K. et al. Identification of human brain tumour initiating cells. Nature 432, 396–401 (2004).
doi: 10.1038/nature03128 pubmed: 15549107
Ignatova, T. N. et al. Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 39, 193–206 (2002).
pubmed: 12203386 doi: 10.1002/glia.10094
Taylor, M. D. et al. Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8, 323–335 (2005).
pubmed: 16226707 doi: 10.1016/j.ccr.2005.09.001
Calabrese, C. et al. A perivascular niche for brain tumor stem cells. Cancer Cell 11, 69–82 (2007).
pubmed: 17222791 doi: 10.1016/j.ccr.2006.11.020
Lathia, J. D., Mack, S. C., Mulkearns-Hubert, E. E., Valentim, C. L. L. & Rich, J. N. Cancer stem cells in glioblastoma. Genes Dev. 29, 1203–1217 (2015).
pubmed: 26109046 pmcid: 4495393 doi: 10.1101/gad.261982.115
Pei, Y. et al. WNT signaling increases proliferation and impairs differentiation of stem cells in the developing cerebellum. Development 139, 1724–1733 (2012).
pubmed: 22461560 pmcid: 3328175 doi: 10.1242/dev.050104
Goodrich, L. V., Milenkovic, L., Higgins, K. M. & Scott, M. P. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277, 1109–1113 (1997).
pubmed: 9262482 doi: 10.1126/science.277.5329.1109
Chen, J. et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488, 522–526 (2012).
pubmed: 22854781 pmcid: 3427400 doi: 10.1038/nature11287
Gibson, P. et al. Subtypes of medulloblastoma have distinct developmental origins. Nature 468, 1095–1099 (2010).
pubmed: 21150899 pmcid: 3059767 doi: 10.1038/nature09587
Johnson, R. A. et al. Cross-species genomics matches driver mutations and cell compartments to model ependymoma. Nature 466, 632–636 (2010).
pubmed: 20639864 pmcid: 2912966 doi: 10.1038/nature09173
Parker, M. et al. C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 506, 451–455 (2014).
pubmed: 24553141 pmcid: 4050669 doi: 10.1038/nature13109
Mohankumar, K. M. et al. An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes. Nat. Genet. 47, 878–887 (2015).
pubmed: 26075792 pmcid: 4520751 doi: 10.1038/ng.3323
Tirosh, I. et al. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature 539, 309–313 (2016).
pubmed: 27806376 pmcid: 5465819 doi: 10.1038/nature20123
Abbott, A. Is ‘friendly fire’ in the brain provoking Alzheimer’s disease? Nature 556, 426–428 (2018).
pubmed: 29691517 doi: 10.1038/d41586-018-04930-7
Sampson, J. H., Maus, M. V. & June, C. H. Immunotherapy for brain tumors. J. Clin. Oncol. 35, 2450–2456 (2017).
pubmed: 28640704 doi: 10.1200/JCO.2017.72.8089
Quail, D. F. & Joyce, J. A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19, 1423–1437 (2013).
pubmed: 24202395 pmcid: 3954707 doi: 10.1038/nm.3394
Griveau, A. et al. A glial signature and Wnt7 signaling regulate glioma-vascular interactions and tumor microenvironment. Cancer Cell 33, 874–889 (2018).
pubmed: 29681511 pmcid: 6211172 doi: 10.1016/j.ccell.2018.03.020
Louveau, A., Harris, T. H. & Kipnis, J. Revisiting the mechanisms of CNS immune privilege. Trends Immunol. 36, 569–577 (2015).
pubmed: 26431936 pmcid: 4593064 doi: 10.1016/j.it.2015.08.006
Tivnan, A., Heilinger, T., Lavelle, E. C. & Prehn, J. H. M. Advances in immunotherapy for the treatment of glioblastoma. J. Neurooncol. 131, 1–9 (2017).
pubmed: 27743144 doi: 10.1007/s11060-016-2299-2
Zacharakis, N. et al. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat. Med. 24, 724–730 (2018).
pubmed: 29867227 pmcid: 6348479 doi: 10.1038/s41591-018-0040-8
Graeber, M. B., Scheithauer, B. W. & Kreutzberg, G. W. Microglia in brain tumors. Glia 40, 252–259 (2002).
pubmed: 12379912 doi: 10.1002/glia.10147
Ginhoux, F. et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841–845 (2010).
pubmed: 20966214 pmcid: 3719181 doi: 10.1126/science.1194637
Hambardzumyan, D., Gutmann, D. H. & Kettenmann, H. The role of microglia and macrophages in glioma maintenance and progression. Nat. Neurosci. 19, 20 (2015).
doi: 10.1038/nn.4185
Razavi, S.-M. et al. Immune evasion strategies of glioblastoma. Front. Surg. 3, 11 (2016).
pubmed: 26973839 pmcid: 4773586 doi: 10.3389/fsurg.2016.00011
Bowman, R. L. & Joyce, J. A. Therapeutic targeting of tumor-associated macrophages and microglia in glioblastoma. Immunotherapy 6, 663–666 (2014).
pubmed: 25041027 doi: 10.2217/imt.14.48
Weller, M. et al. Vaccine-based immunotherapeutic approaches to gliomas and beyond. Nat. Rev. Neurol. 13, 363–374 (2017).
pubmed: 28497804 doi: 10.1038/nrneurol.2017.64
Campbell, B. B. et al. Comprehensive analysis of hypermutation in human cancer. Cell 171, 1042–1056 (2017).
pubmed: 29056344 pmcid: 5849393 doi: 10.1016/j.cell.2017.09.048
Banks, W. A. From blood–brain barrier to blood–brain interface: new opportunities for CNS drug delivery. Nat. Rev. Drug Discov. 15, 275 (2016).
pubmed: 26794270 doi: 10.1038/nrd.2015.21
Larochelle, C. et al. EGFL7 reduces CNS inflammation in mouse. Nat. Commun. 9, 819 (2018).
pubmed: 29483510 pmcid: 5827652 doi: 10.1038/s41467-018-03186-z
Hawkins, B. T. & Davis, T. P. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev. 57, 173–185 (2005).
pubmed: 15914466 doi: 10.1124/pr.57.2.4
Daneman, R., Zhou, L., Kebede, A. A. & Barres, B. A. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468, 562–566 (2010).
pubmed: 20944625 pmcid: 3241506 doi: 10.1038/nature09513
Abbott, N. J., Ronnback, L. & Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 7, 41–53 (2006).
pubmed: 16371949 doi: 10.1038/nrn1824
Vanlandewijck, M. et al. A molecular atlas of cell types and zonation in the brain vasculature. Nature 554, 475–480 (2018).
doi: 10.1038/nature25739 pubmed: 29443965
Kung, Y. et al. Focused shockwave induced blood-brain barrier opening and transfection. Sci. Rep. 8, 2218 (2018).
pubmed: 29396523 pmcid: 5797245 doi: 10.1038/s41598-018-20672-y
Pajtler, K. W. et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 27, 728–743 (2015).
pubmed: 25965575 pmcid: 4712639 doi: 10.1016/j.ccell.2015.04.002
Jacus, M. O. et al. Pharmacokinetic properties of anticancer agents for the treatment of central nervous system tumors: update of the literature. Clin. Pharmacokinet. 55, 297–311 (2016).
pubmed: 26293618 pmcid: 4761278 doi: 10.1007/s40262-015-0319-6
Carpentier, A. et al. Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci. Transl Med. 8, 343re342 (2016).
doi: 10.1126/scitranslmed.aaf6086
Rosso, L. et al. A new model for prediction of drug distribution in tumor and normal tissues: pharmacokinetics of temozolomide in glioma patients. Cancer Res. 69, 120–127 (2009).
pubmed: 19117994 doi: 10.1158/0008-5472.CAN-08-2356
Hubert, C. G. et al. A three-dimensional organoid culture system derived from human glioblastomas recapitulates the hypoxic gradients and cancer stem cell heterogeneity of tumors found in vivo. Cancer Res. 76, 2465–2477 (2016).
pubmed: 26896279 pmcid: 4873351 doi: 10.1158/0008-5472.CAN-15-2402
Toledo, C. M. et al. Genome-wide CRISPR-Cas9 screens reveal loss of redundancy between PKMYT1 and WEE1 in glioblastoma stem-like cells. Cell Rep. 13, 2425–2439 (2015).
pubmed: 26673326 pmcid: 4691575 doi: 10.1016/j.celrep.2015.11.021
Atkinson, J. M. et al. An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma. Cancer Cell 20, 384–399 (2011).
pubmed: 21907928 pmcid: 3172881 doi: 10.1016/j.ccr.2011.08.013
Housden, B. E. et al. Improved detection of synthetic lethal interactions in Drosophila cells using variable dose analysis (VDA). Proc. Natl Acad. Sci. USA 114, E10755–E10762 (2017).
pubmed: 29183982 doi: 10.1073/pnas.1713362114 pmcid: 5740648
Pitter, K. L. et al. Corticosteroids compromise survival in glioblastoma. Brain 139, 1458–1471 (2016).
pubmed: 27020328 pmcid: 5006251 doi: 10.1093/brain/aww046
Krueger, D. A. et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N. Engl. J. Med. 363, 1801–1811 (2010).
pubmed: 21047224 doi: 10.1056/NEJMoa1001671
Kieran, M. W. et al. CNS tumours: the first study of dabrafenib in pediatric patients with BRAF V600–mutant relapsed or refractory low-grade gliomas [abstract]. Ann. Oncol. 27 (Suppl. 6), LBA19_PR (2016).
Singh, D. et al. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science 337, 1231–1235 (2012).
pubmed: 22837387 pmcid: 3677224 doi: 10.1126/science.1220834
Northcott, P. A. et al. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511, 428–434 (2014).
pubmed: 25043047 pmcid: 4201514 doi: 10.1038/nature13379
Schwartzentruber, J. et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482, 226–231 (2012).
pubmed: 22286061 doi: 10.1038/nature10833
Wu, X. et al. Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature 482, 529–533 (2012).
pubmed: 22343890 pmcid: 3288636 doi: 10.1038/nature10825
Morrissy, A. S. et al. Divergent clonal selection dominates medulloblastoma at recurrence. Nature 529, 351–357 (2016).
pubmed: 26760213 pmcid: 4936195 doi: 10.1038/nature16478
Wang, J. et al. Clonal evolution of glioblastoma under therapy. Nat. Genet. 48, 768–776 (2016).
pubmed: 27270107 pmcid: 5627776 doi: 10.1038/ng.3590
Patel, A. P. et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344, 1396–1401 (2014).
pubmed: 24925914 pmcid: 4123637 doi: 10.1126/science.1254257
Darmanis, S. et al. Single-cell RNA-seq analysis of infiltrating neoplastic cells at the migrating front of human glioblastoma. Cell Rep. 21, 1399–1410 (2017).
pubmed: 29091775 pmcid: 5810554 doi: 10.1016/j.celrep.2017.10.030
Brindle, K. M., Izquierdo-Garcia, J. L., Lewis, D. Y., Mair, R. J. & Wright, A. J. Brain tumor imaging. J. Clin. Oncol. 35, 2432–2438 (2017).
pubmed: 28640699 doi: 10.1200/JCO.2017.72.7636
Fowler, D. M. & Fields, S. Deep mutational scanning: a new style of protein science. Nat. Methods 11, 801 (2014).
pubmed: 25075907 pmcid: 4410700 doi: 10.1038/nmeth.3027
Louis, D. N. et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 131, 803–820 (2016).
pubmed: 27157931 doi: 10.1007/s00401-016-1545-1
Pajtler, K. W. et al. The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol. 133, 5–12 (2017).
pubmed: 27858204 doi: 10.1007/s00401-016-1643-0
Aldape, K., Zadeh, G., Mansouri, S., Reifenberger, G. & von Deimling, A. Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol. 129, 829–848 (2015).
pubmed: 25943888 doi: 10.1007/s00401-015-1432-1
Sturm, D. et al. New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell 164, 1060–1072 (2016).
pubmed: 26919435 pmcid: 5139621 doi: 10.1016/j.cell.2016.01.015
Capper, D. et al. DNA methylation-based classification of central nervous system tumours. Nature 555, 469–474 (2018).
pubmed: 29539639 pmcid: 6093218 doi: 10.1038/nature26000
Reinartz, R. et al. Functional subclone profiling for prediction of treatment-induced intratumor population shifts and discovery of rational drug combinations in human glioblastoma. Clin. Cancer Res. 23, 562–574 (2017).
pubmed: 27521447 doi: 10.1158/1078-0432.CCR-15-2089
Day, S. E. et al. Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1–13C]pyruvate and 13C magnetic resonance spectroscopic imaging. Magn. Reson. Med. 65, 557–563 (2011).
pubmed: 21264939 doi: 10.1002/mrm.22698
Wan, J. C. M. et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat. Rev. Cancer 17, 223–238 (2017).
pubmed: 28233803 doi: 10.1038/nrc.2017.7
Pentsova, E. I. et al. Evaluating cancer of the central nervous system through next-generation sequencing of cerebrospinal fluid. J. Clin. Oncol. 34, 2404–2415 (2016).
pubmed: 27161972 pmcid: 4981784 doi: 10.1200/JCO.2016.66.6487
Wen, P. Y. et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J. Clin. Oncol. 28, 1963–1972 (2010).
pubmed: 20231676 doi: 10.1200/JCO.2009.26.3541
Moxon-Emre, I. et al. Intellectual outcome in molecular subgroups of medulloblastoma. J. Clin. Oncol. 34, 4161–4170 (2016).
pubmed: 27507873 doi: 10.1200/JCO.2016.66.9077
Duffner, P. K. et al. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N. Engl. J. Med. 328, 1725–1731 (1993).
pubmed: 8388548 doi: 10.1056/NEJM199306173282401
Packer, R. J. et al. Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: a Children’s Cancer Group Study. J. Clin. Oncol. 17, 2127–2136 (1999).
pubmed: 10561268 doi: 10.1200/JCO.1999.17.7.2127
Geyer, J. R. et al. Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J. Clin. Oncol. 23, 7621–7631 (2005).
pubmed: 16234523 doi: 10.1200/JCO.2005.09.095
Ater, J. L. et al. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children’s Oncology Group. J. Clin. Oncol. 30, 2641–2647 (2012).
pubmed: 22665535 pmcid: 3413276 doi: 10.1200/JCO.2011.36.6054
Krishnatry, R. et al. Clinical and treatment factors determining long-term outcomes for adult survivors of childhood low-grade glioma: a population-based study. Cancer 122, 1261–1269 (2016).
pubmed: 26970559 doi: 10.1002/cncr.29907
Cole, P. D. et al. Polymorphisms in genes related to oxidative stress are associated with inferior cognitive function after therapy for childhood acute lymphoblastic leukemia. J. Clin. Oncol. 33, 2205–2211 (2015).
pubmed: 25987702 pmcid: 4477790 doi: 10.1200/JCO.2014.59.0273
Xu, H. et al. Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss. Nat. Genet. 47, 263–266 (2015).
pubmed: 25665007 pmcid: 4358157 doi: 10.1038/ng.3217
Lim, D. A. & Alvarez-Buylla, A. The adult ventricular–subventricular zone (V-SVZ) and olfactory bulb (OB) neurogenesis. Cold Spring Harb. Perspect. Biol. 8, a018820 (2016).
pubmed: 27048191 pmcid: 4852803 doi: 10.1101/cshperspect.a018820

Auteurs

Kenneth Aldape (K)

Department of Pathology, University Health Network, Toronto, Ontario, Canada.

Kevin M Brindle (KM)

CRUK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.

Louis Chesler (L)

The Institute of Cancer Research, London, UK.

Rajesh Chopra (R)

The Institute of Cancer Research, London, UK.

Amar Gajjar (A)

Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.

Mark R Gilbert (MR)

Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

Nicholas Gottardo (N)

Telethon Kids Institute, Subiaco, WA, Australia.

David H Gutmann (DH)

Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.

Darren Hargrave (D)

Great Ormond Street Hospital for Children, London, UK.

Eric C Holland (EC)

Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

David T W Jones (DTW)

Pediatric Glioma Research Group, Hopp Children's Cancer Center at the NCT Heidelberg, Heidelberg, Germany.

Johanna A Joyce (JA)

Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.

Pamela Kearns (P)

Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.

Mark W Kieran (MW)

Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA, USA.

Ingo K Mellinghoff (IK)

Human Oncology and Pathogenesis Program and Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Melinda Merchant (M)

Oncology, AstraZeneca IMED Biotech Unit, Boston, MA, USA.

Stefan M Pfister (SM)

Division of Pediatric Oncology, Hopp Children's Cancer Center at the NCT Heidelberg, Heidelberg, Germany.

Steven M Pollard (SM)

Cancer Research UK Edinburgh Centre and Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.

Vijay Ramaswamy (V)

Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
ORCID: 0000-0002-6557-895X

Jeremy N Rich (JN)

Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, CA, USA.

Giles W Robinson (GW)

Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
ORCID: 0000-0001-7441-9486

David H Rowitch (DH)

Department of Paediatrics, University of Cambridge and Wellcome Trust-MRC Stem Cell Institute, Cambridge, UK.

John H Sampson (JH)

The Preston Robert Tisch Brain Tumor Center, Duke Cancer Center, Durham, NC, USA.

Michael D Taylor (MD)

The Arthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.

Paul Workman (P)

The Institute of Cancer Research, London, UK.

Richard J Gilbertson (RJ)

CRUK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK. richard.gilbertson@cruk.cam.ac.uk.
CRUK Cambridge Institute and Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Cambridge, UK. richard.gilbertson@cruk.cam.ac.uk.
ORCID: 0000-0001-7539-9472

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Challenges to curing primary brain tumours.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Challenges to curing primary brain tumours.