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Molecular Neurooncology and Neoangiogenesis of Malignant Gliomas

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Therapeutic Ribonucleic Acids in Brain Tumors

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Abstract

Malignant gliomas are the most common and most aggressive primary brain tumors in adults. Advances in surgery, radiotherapy and chemotherapy only have a minor impact on the natural course of these tumors. Due to the dismal prognosis of malignant glioma patients, there is an urgent need for new innovative treatments based on a better understanding of the molecular mechanisms of gliomagenesis. Many growth factors, growth factor receptors – usually receptor tyrosine kinases – and receptor-associated intracellular signaling pathways are critically involved in glioma growth, invasiveness and tumor neovascularization.

Therefore, this chapter highlights the most important signaling pathways involved in initiation and progression of malignant gliomas. The knowledge of these pathways is the rationale of several concepts of new innovative molecular therapies in modern neurooncology.

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Abbreviations

AAC:

Anaplastic astrocytoma

AG:

Anaplastic glioma

AOD:

Anaplastic oligodendroglioma

ASO:

Antisense oligonucleotide

ClR:

Clinical response

CR:

Complete response

DAG:

Diacylglycerol

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

ERK:

Extracellular signal regulated kinase

FGF:

Fibroblast growth factor

FGFR:

Fibroblast growth factor receptor

GBM:

Glioblastoma multiforme

GF:

Growth factor

Grb2:

Growth factor receptor-bound protein 2

IGF:

Insulin growth factor

IGFR:

Insulin growth factor receptor

LT:

Ligand linked targeted toxins

mAB:

Neutralizing monoclonal antibody

MAPK:

Mitogen-activated protein kinase

MEK:

MAPK/ERK kinase

mTOR:

Mammalian target of rapamycin

PD:

Progressive disease

PDGF:

Platelet-derived growth factor

PDGFR:

Platelet-derived growth factor receptor

PI3K:

Phosphatidyl-inositol-3-kinase

PKC:

Proteinkinase C

PLC:

Phospholipase C

PR:

Partial response

rAAC:

Recurrent anaplastic astrocytoma

Ras-GAP:

GTPase-activating protein of Ras

Ras-GTP:

Ras-guanosine-triphosphate, active Ras

rGBM:

Recurrent glioblastoma multiforme

rHGG:

Recurrent high grade Glioma

RTK:

Receptor tyrosine kinase

SD:

Stable disease

SR:

Soluble receptor

SMI-R:

Small molecule inhibitor of receptors

SMI-S:

Small molecule inhibitor of intracellular signaling molecules

TGF:

Transforming growth factor

TGFR:

Transforming growth factor receptor

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  1. Department of Neurology (Neurooncology Group), Medical University of Innsbruck, Anichstrasse 35, A-6020, Innsbruck, Austria

    Markus Hutterer & Günther Stockhammer

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  1. Markus Hutterer
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  2. Günther Stockhammer
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Correspondence to Markus Hutterer .

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  1. Inst. Chemie und Biochemie, FU Berlin, Thielallee 63, Berlin, 14195, Germany

    Volker A. Erdmann

  2. Inst. Neuropathologie, Universitätsklinikum Düsseldorf, Moorenstr. 5, Düsseldorf, 40225, Germany

    Guido Reifenberger

  3. Inst. Bioorganic Chemistry, PAN Poznan, ul. Z. Noskowskiego 12/14, Poznan, 61-704, Poland

    Jan Barciszewski

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Hutterer, M., Stockhammer, G. (2009). Molecular Neurooncology and Neoangiogenesis of Malignant Gliomas. In: Erdmann, V., Reifenberger, G., Barciszewski, J. (eds) Therapeutic Ribonucleic Acids in Brain Tumors. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00475-9_2

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