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Resistance of Glioblastomas to Radiation Therapy

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Resistance to Targeted Therapies Against Adult Brain Cancers

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT))

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Abstract

Glioblastoma is the most lethal primary brain tumour with a median survival of 12–14 months because of resistance to radiotherapy and other chemotherapies. Ionising radiation represents the most effective treatment for glioblastoma, but radiotherapy remains only palliative due to radioresistance. The mechanism of radioresistance in glioblastomas is a complex phenomenon and has been extensively studied in the last decade, and effective radiosensitisers have always been sought experimentally. The radiosensitivity of tumour cells is regulated by a series of internal factors, such as cell cycle arrest, cell apoptosis and DNA damage. In addition, the existence of glioma stem cells and their growing microenvironment also play an important role in radioresistance. In this chapter, we will summarise the proposed mechanisms of radioresistance in glioma cells and also review how the therapeutic strategies can be developed to target these mechanisms for an improved radiosensitisation of these aggressive brain tumours.

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Abbreviations

2-DG:

2-Deoxy-D-glucose

3-BP:

3-Bromopyruvate

3D:

Three dimensional

ATP:

Adenosine triphosphate

bFGF:

Basic fibroblast growth factor

DCA:

Dichloroacetate

DNA:

Deoxyribonucleic acid

ECM:

Extracellular matrix

GSH:

Glutathione

GSSH:

Oxidised glutathione

Gy:

Grey

H2AX:

Phosphorylated histone

HIF:

Hypoxia-inducible factor

HK:

Hexokinase

NADP:

Nicotinamide adenine dinucleotide phosphate

PARP:

Poly(ADP-ribose)polymerase

PDH:

Pyruvate dehydrogenase

PDK1:

Pyruvate dehydrogenase kinase 1

ROS:

Reactive oxygen species

VEGF:

Vascular endothelial growth factor

WHO:

World Health Organization

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  1. Targeted Therapies Research Program, Children’s Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Randwick, NSW, 2031, Australia

    Han Shen BMed

  2. Cancer Care Centre, St George Hospital, Kogarah, NSW, 2217, Australia

    Eric Hau

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  1. Centre for Systems Medicine, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland

    Amanda Tivnan

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Shen, H., Hau, E. (2016). Resistance of Glioblastomas to Radiation Therapy. In: Tivnan, A. (eds) Resistance to Targeted Therapies Against Adult Brain Cancers. Resistance to Targeted Anti-Cancer Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-46505-0_3

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