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Targeting Chemotherapy Resistance in Glioblastoma Through Modulation of ABC Transporters

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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 (GBM) is a highly aggressive Grade IV solid central nervous system neoplasm with an incidence rate of 3–4 per 100,000 people worldwide and the average 5-year survival rate of GBM patients is less than 5 %, leading to the fact that GBM is the most lethal form of brain tumor. The presence of several adenosine triphosphate-binding cassette (ABC) transporters is thought to contribute to the sustained progression of GBM tumours, inhibiting and rapidly removing anticancer drugs from GBM tumour cells. ABC transporters are transmembrane pumps which use ATP hydrolysis to facilitate translocation of substrates across cellular membranes. Overexpression of ABC transporters including P-gp (ABCB1), ABCCs, or MRPs and breast cancer-resistance protein (BCRP, ABCG2) on the GBM cells themselves is thought to instill chemoresistance and active drug extrusion at the tumor site rendering the temporal effect of successfully administered drugs negligible, if at all. In this regard, the role of individual ABC transporters and their contribution to chemoresistance and potential as targeted therapies of GBM chemosensitization will be discussed in this chapter.

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Abbreviations

ATP:

Adenosine triphosphate

ATPase:

Adenosine triphosphatase

B-BB:

Blood-brain barrier

B-CFB:

Blood-cerebrospinal fluid barrier

B-TB:

Blood-tumor barrier

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

EGF:

Epithelial growth factor

Gy:

Gray (unit of ionizing radiation)

PD-1:

Programmed cell death protein 1

VEGF:

Vascular endothelial growth factor

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  1. Royal College of Surgeons in Ireland, 123 St Stephen’s Green, Dublin 2, Ireland

    Amanda Tivnan PhD

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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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Tivnan, A. (2016). Targeting Chemotherapy Resistance in Glioblastoma Through Modulation of ABC Transporters. 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_2

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