[Frontiers in Bioscience 7, e339-353, August 1, 2002]

APOPTOSIS IN GLIOMAS, AND ITS ROLE IN THEIR CURRENT AND FUTURE TREATMENT

Oliver Bögler 1 and Michael Weller 2

1 William and Karen Davidson Laboratory of Brain Tumor Biology, Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA, 2 Laboratory of Molecular Neuro-Oncology, Department of Neurology, University of Tübingen, School of Medicine, Tübingen, Germany

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Concepts of Cell Death
2.2. A Brief Introduction to the Pathways of Apoptosis
3. Apoptosis in Gliomagenesis
3.1. Life or death decisions
3.2. Does apoptosis correlate with malignancy in brain tumors?
3.3. Do existing treatments for glioma rely on the induction of apoptosis?
4. Apoptosis pathways - new molecules, new targets
4.1. Death Ligands, Receptors and Downstream Effectors
4.2. Bcl-2 family
4.3. Treatment combinations
5. Perspective
6. Acknowledgements
7. References

1. ABSTRACT

Apoptosis has recently entered the spotlight in the continuing search for new therapeutic approaches to cancer because it plays a twofold role in this disease. As stated by Lowe and Lin: "(M)ost cytotoxic anticancer agents induce apoptosis (and so) the same mutations that suppress apoptosis during tumor development also reduce treatment sensitivity" (1). Therefore, any strategy aimed at increasing the propensity of glioma cells to undergo apoptosis could be therapeutic in its own right, but has the added potential of enhancing their sensitivity to other, established, treatments. As a corollary, understanding apoptotic mechanisms at the molecular level will not only help to explain why gliomas arise, but also identify points of intervention. This review will focus on these points, with emphasis on two families of apoptotic molecules, death ligands and their receptors, and BCL-2 family proteins. Near-term strategies of how apoptosis can be exploited therapeutically are discussed.