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Journal of Neuro-Oncology
Published in: Journal of Neuro-Oncology 3/2016

01-02-2016 | Topic Review

How to train glioma cells to die: molecular challenges in cell death

Authors: Jeffrey Wojton, Walter Hans Meisen, Balveen Kaur

Published in: Journal of Neuro-Oncology | Issue 3/2016

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Abstract

The five-year survival rate for patients with malignant glioma is less than 10 %. Despite aggressive chemo/radiotherapy these tumors have remained resistant to almost every interventional strategy evaluated in patients. Resistance to these agents is attributed to extrinsic mechanisms such as the tumor microenvironment, poor drug penetration, and tumoral heterogeneity. In addition, genetic and molecular examination of these tumors has revealed defective apoptotic regulation, enhanced pro-survival autophagy signaling, and a propensity for necrosis that aids in the adaptation to environmental stress and resistance to treatment. The combination of extrinsic and intrinsic hallmarks in glioma contributes to the multifaceted resistance to traditional anti-tumor agents. Here we describe the biology of the disease relevant to therapeutic resistance, with a specific focus on molecular deregulation of cell death pathways. Emerging studies investigating the targeting of these pathways including BH3 mimetics and autophagy inhibitors that are being evaluated in both the preclinical and clinical settings are discussed. This review highlights the pathways exploited by glioblastoma cells that drive their hallmark pro-survival predisposition and makes therapy development such a challenge.
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Metadata
Title
How to train glioma cells to die: molecular challenges in cell death
Authors
Jeffrey Wojton
Walter Hans Meisen
Balveen Kaur
Publication date
01-02-2016
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-015-1980-1

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