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Targeted therapy for brain tumours

Nature Reviews Drug Discovery volume 3, pages 499–508 (2004)Cite this article

Key Points

  • Brain tumours represent a heterogeneous group of neoplasms, the most common being astrocytomas. Astrocytomas differ in their spectrum of behaviour, from those which are relatively benign to the most malignant, glioblastoma multiforme.

  • Due to their micro-environment within the central nervous system, brain tumours are well isolated from systemic circulation. This occurs because of the presence of the blood–brain barrier, the blood–cerebrospinal fluid barrier, and blood–tumour barrier. As such, systemic therapy of brain tumours has been unsuccessful.

  • The development of biodegradable polymers has changed the therapy of patients with brain tumours. Local and controlled delivery of antineoplastic agents such as Gliadel has overcome the inherent obstacles presented by the barriers of the central nervous system.

  • New advances in technology, gene therapy and immunology are likely to have a significant impact on the treatment of malignant brain tumours in the near future.

Abstract

Although previously considered untreatable, brain tumours no longer carry the same prognosis as they did even a decade ago. Recent advances in drug delivery to the central nervous system have not only bypassed physiological constraints such as the blood–brain barrier, but have, in fact, changed the course of treatment for patients with malignant brain tumours. The creation of targeted therapies, which spare normal tissue and destroy tumour cells, is changing the field of neuro-oncology. In this article, we review recent developments in the delivery of drugs to tumours of the central nervous system, discuss current trends and directions in the development of novel drugs and delivery systems, and present new and cutting-edge strategies for overcoming the challenges ahead.

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Figure 1: Development and progression of astrocytic brain tumours.
Figure 2: The blood–brain barrier.
Figure 3: Chemotherapeutic drugs and experimental neurological agents.
Figure 4: Implantation of Gliadel.

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Acknowledgements

The research presented in this work has been supported in part by the National Cooperative Drug Discovery Group of the National Cancer Institute.

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Authors and Affiliations

  1. Division of Neurosurgery, The University of Chicago Pritzker School of Medicine, 5841 South Maryland Avenue-MC 3026, Chicago, 60637, Illinois, USA

    Maciej S. Lesniak

  2. Departments of Neurosurgery and Oncology, The Johns Hopkins University School of Medicine, Hunterian 817, 725 North Wolfe Street, Baltimore, 21205, Maryland, USA

    Henry Brem

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Competing interests

Under a licensing agreement between Guilford Pharmaceuticals and the Johns Hopkins University, H.B. is entitled to a share of royalty received by the University on sales of products described in this work. H.B. and the University own Guilford Pharmaceuticals stock, which is subject to certain restrictions under University policy. H.B. is also a paid consultant to Guilford Pharmaceuticals. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest polices.

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DATABASES

Entrez Gene

ABCB1

ATP-binding cassette C1

bFGF

O6-methylguanine-DNA methyltransferase

VEGF

FURTHER INFORMATION

American Brain Tumor Association

Controlled Release Society

MIT Program in Polymer Science and Technology

National Academy of Engineering

Neurosurgery

Society for Biomaterials

Encyclopedia of Life Sciences

Brain cancers

Glossary

SURGICAL DEBULKING

A surgical procedure in which part of the tumour is removed, as opposed to the entire tumour.

BLOOD–BRAIN BARRIER

A state of physiological, metabolic and biochemical processes that distinguish the cerebral capillary endothelium from the endothelium of systemic organ systems. It is formed by tight junctions of cerebral capillary endothelial cells.

TRANSCYTOSIS

The transport of material across an epithelium by uptake on one face into a coated vesicle, which then can be transported to the opposite face in another vesicle.

PARENCHYMA

Tissue that constitutes the essential part of an organ, as contrasted with connective tissue and blood vessels.

ARTERIOVENOUS SHUNTS

A passage by which blood is directly diverted from the arterial side to the venous side.

VENOUS ANASTOMOSES

Communication between two or more veins forming a network of vessels.

LIPOSOMES

Synthetic, uniform, bilayer lipid membrane vesicles formed by emulsification of cell membranes in dilute salt solutions. Liposomes are being developed as an approach for drug delivery in which toxic drugs are 'wrapped' inside a liposome and tagged with an organ-specific antibody.

OMMAYA RESERVOIR

A device with a fluid reservoir implanted under the scalp with a catheter inside a ventricle. It allows for medication to be given directly to the cerebrospinal fluid and into the brain.

HAZARD RATIO

A summary of the difference between two survival curves, representing the reduction in the risk of death on treatment compared with control, during the period of follow up.

KARNOFSKY PERFORMANCE STATUS

A standard way of measuring the ability of cancer patients to perform ordinary tasks.

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Lesniak, M., Brem, H. Targeted therapy for brain tumours. Nat Rev Drug Discov 3, 499–508 (2004). https://doi.org/10.1038/nrd1414

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