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Resistance to Targeted Therapies Against Adult Brain Cancers pp 89–105Cite as

Resistance of Brain Tumours to Small-Molecule-Targeted Therapies: Lessons from Various Cancer Types

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

Abstract

Brain tumours are a heterogeneous group of central nervous system (CNS) neoplasms. The current treatment regime for brain tumours consists of surgical resection or sequential or concurrent chemoradiotherapy with chemotherapy such as temozolomide. Despite improvements in these treatments, survival rate is less than 10 % 5 years after diagnosis, and there are limited second-line treatments available. Although recent improvements in understanding the genomics of brain tumours such as glioblastomas (GBMs) have implicated several pathways, clinical success of targeted therapies has been limited. This is due in part to resistance (both intrinsic and acquired) to the therapies but also in part due to the intratumoural heterogeneity, limited vasculature, lack of CNS penetration and the blood-brain barrier limiting the efficacy of the agent. The use of targeted therapies has come to the forefront of oncology in the past decade. Monoclonal antibodies and small-molecule-targeted therapies such as tyrosine kinase inhibitors are currently being used for the treatment of a number of receptor and pathway alteration-driven forms of cancer. Resistance to targeted therapies has been the Achilles heel of the successful application of these emerging agents. By investigating the response to these therapies in many cancer types and examining any mechanisms of resistance, they may be utilised in the treatment of brain tumours.

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Abbreviations

ADC:

Antibody drug conjugate

CML:

Chronic myeloid leukaemia

CNS:

Central nervous system

EGFR:

Epidermal growth factor

EIADS:

Enzyme-inducing antiepileptic drugs

ERK/MAPK:

Extracellular-signal-regulated kinase/mitogen-activated protein kinase

HER2:

Human epidermal receptor 2

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PDGFR:

Platelet-derived growth factor receptor

PFS:

Progression-free survival

PI3K:

Phosphatidylinositol 3-kinases

RCC:

Renal cell carcinoma

RTK:

Receptor tyrosine kinase

TKI:

Tyrosine kinase inhibitor

TMZ:

Temozolomide

TRAIL:

TNF-related apoptosis-inducing ligand

VEGFR:

Vascular growth factor receptor

WHO:

World Health Organization

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Acknowledgement 

The author wishes to acknowledge and thank Dr. Patrick Morris for his assistance.

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  1. National Institute for Cellular Biotechnology, DCU, Collins Avenue, Dublin 9, Ireland

    Fiona O’Neill

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  1. Fiona O’Neill
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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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O’Neill, F. (2016). Resistance of Brain Tumours to Small-Molecule-Targeted Therapies: Lessons from Various Cancer Types. 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_5

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