Tumour Microenvironment in Paediatric Brain Tumour

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Developmental Neuroscience".

Deadline for manuscript submissions: closed (20 April 2020) | Viewed by 16017

Special Issue Editors


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Guest Editor
Paediatric Neuro-Oncology Laboratory, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK
Interests: CNS tumours; neurobiology; blood–brain barrier; neurosciences; neurodevelopment; epigenetics; gene regulation; tumour cell invasion; angiogenesis
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Guest Editor
Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Department of Pathology, 3333 Burnet Ave., Location R, MLC 1035, Cincinnati, OH 45229, USA

Special Issue Information

Dear Colleagues,

Brain tumours are the leading cause of cancer-related death in children, with gliomas accounting for 55% of paediatric CNS tumours. The choreography of numerous components of the developing brain microenvironment are necessary for successful connections and the ultimate functioning of neural networks. Cancers do not grow on their own and we believe that insight into the microenvironment of the developing central nervous system (CNS) is critical for identifying drivers of tumour growth and therapeutic resistance in paediatric brain cancers. Lacking somewhat in the literature, is how components of the tumour microenvironment (which change during tumour growth and in response to therapy) and a developing brain interact to support tumour growth, resistance, adaptation and recurrence. We believe that this area of work holds critical information for a major shift in the ways these tumours are treated.

In this Special Issue on "Tumour Microenvironment in Paediatric Brain Tumour", we would like to invite manuscripts on a variety of topics related to host tumour interactions in paediatric brain cancers. Manuscripts on basic molecular science (genetics, epigenetics, and metabolism), molecular/signalling drivers, immunologic perspectives, physical/mechanical perspectives, flow dynamics (vascular and CSF), future perspectives on translational and therapeutic considerations are welcome. We believe that the works published in this Special Issues will provide another stepping stone to new insights. By understanding the developing brain in context with tumour initiation and growth, new therapeutic targets will be realised. We look forward to your submissions.

Dr. Helen L. Fillmore
Prof. Christine Fuller
Guest Editors

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Keywords

  • Brain development
  • Tumour micro-environment
  • Metabolism
  • Host–tumour interactions
  • Immune system
  • Angiogenesis
  • Invasion
  • CSF–ventricular system
  • Blood–brain barrier
  • Tumour cell of origin

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Published Papers (2 papers)

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Review

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15 pages, 1949 KiB  
Review
Intersection of Brain Development and Paediatric Diffuse Midline Gliomas: Potential Role of Microenvironment in Tumour Growth
by Katie F. Loveson and Helen L. Fillmore
Brain Sci. 2018, 8(11), 200; https://doi.org/10.3390/brainsci8110200 - 16 Nov 2018
Cited by 13 | Viewed by 10895
Abstract
Diffuse intrinsic pontine glioma (DIPG) is a devastating and incurable paediatric brain tumour with a median overall survival of 9 months. Until recently, DIPGs were treated similarly to adult gliomas, but due to the advancement in molecular and imaging technologies, our understanding of [...] Read more.
Diffuse intrinsic pontine glioma (DIPG) is a devastating and incurable paediatric brain tumour with a median overall survival of 9 months. Until recently, DIPGs were treated similarly to adult gliomas, but due to the advancement in molecular and imaging technologies, our understanding of these tumours has increased dramatically. While extensive research is being undertaken to determine the function of the molecular aberrations in DIPG, there are significant gaps in understanding the biology and the influence of the tumour microenvironment on DIPG growth, specifically in regards to the developing pons. The precise orchestration and co-ordination of the development of the brain, the most complex organ in the body, is still not fully understood. Herein, we present a brief overview of brainstem development, discuss the developing microenvironment in terms of DIPG growth, and provide a basis for the need for studies focused on bridging pontine development and DIPG microenvironment. Conducting investigations in the context of a developing brain will lead to a better understanding of the role of the tumour microenvironment and will help lead to identification of drivers of tumour growth and therapeutic resistance. Full article
(This article belongs to the Special Issue Tumour Microenvironment in Paediatric Brain Tumour)
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8 pages, 227 KiB  
Perspective
A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen
by Richard E. Kast, Alex P. Michael, Iacopo Sardi, Terry C. Burns, Tim Heiland, Georg Karpel-Massler, Francois G. Kamar and Marc-Eric Halatsch
Brain Sci. 2020, 10(1), 51; https://doi.org/10.3390/brainsci10010051 - 17 Jan 2020
Cited by 9 | Viewed by 4470
Abstract
Prognosis for diffuse intrinsic pontine glioma (DIPG) and generally for diffuse midline gliomas (DMG) has only marginally improved over the last ~40 years despite dozens of chemotherapy and other therapeutic trials. The prognosis remains invariably fatal. We present here the rationale for a [...] Read more.
Prognosis for diffuse intrinsic pontine glioma (DIPG) and generally for diffuse midline gliomas (DMG) has only marginally improved over the last ~40 years despite dozens of chemotherapy and other therapeutic trials. The prognosis remains invariably fatal. We present here the rationale for a planned study of adding 5-aminolevulinic acid (5-ALA) to the current irradiation of DIPG or DMG: the 5aai regimen. In a series of recent papers, oral 5-ALA was shown to enhance standard therapeutic ionizing irradiation. 5-ALA is currently used in glioblastoma surgery to enable demarcation of overt tumor margins by virtue of selective uptake of 5-ALA by neoplastic cells and selective conversion to protoporphyrin IX (PpIX), which fluoresces after excitation by 410 nm (blue) light. 5-ALA is also useful in treating glioblastomas by virtue of PpIX’s transfer of energy to O2 molecules, producing a singlet oxygen that in turn oxidizes intracellular DNA, lipids, and proteins, resulting in selective malignant cell cytotoxicity. This is called photodynamic treatment (PDT). Shallow penetration of light required for PpIX excitation and resultant energy transfer to O2 and cytotoxicity results in the inaccessibility of central structures like the pons or thalamus to sufficient light. The recent demonstration that keV and MeV photons can also excite PpIX and generate singlet O2 allows for reconsideration of 5-ALA PDT for treating DMG and DIPG. 5-ALA has an eminently benign side effect profile in adults and children. A pilot study in DIPG/DMG of slow uptitration of 5-ALA prior to each standard irradiation session—the 5aai regimen—is warranted. Full article
(This article belongs to the Special Issue Tumour Microenvironment in Paediatric Brain Tumour)
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