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Cell Death Signaling in Glioblastoma Multiforme: Role of the Bcl2L12 Oncoprotein

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Tumors of the Central Nervous System, Volume 1

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 1))

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Abstract

Malignant glioma (MG) represents the most prevalent and lethal primary central nervous system cancer. Despite aggressive surgical resection and treatment regimens, patients diagnosed with the highest grade MG, grade IV glioblastoma multiforme (GBM), survive for only 9–12 months after diagnosis. Multimodal approaches using radiation with conjunctive chemotherapy (temozolamide) resulted in only marginal increase in patients’ survival up to 14.6 months. An incomplete understanding of how catalogued genetic aberrations dictate phenotypic hallmarks of the disease, particularly intense therapy (apoptosis) resistance, yet florid intratumoral necrogenesis, combined with a highly therapy-resistant cancer stem cell population (brain tumor stem cells, BTSC) as the putative cell-of-origin conspired to make GBM a highly enigmatic and incurable disease. Especially the continued lack of success in treating high-grade gliomas with targeted (receptor) tyrosine kinase inhibitors, which have been proven to be effective in other malignancies, has prompted a reevaluation of all aspects of glioma drug development and underlined the overarching need to identify and molecularly dissect genetic aberrations in cellular survival pathways that play pivotal roles in GBM’s profound therapy resistance. This review focuses on apoptosis and necrosis pathways implicated in GBM development and evasion from therapy-induced cell death, and discusses the roles and potential therapeutical applications of the novel Bcl-2-like oncoprotein Bcl2L12 in driving cell death-related phenotypes in GBM.

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Authors and Affiliations

  1. Department of Neurology, The Robert H. Lurie Comprehensive Cancer Center, The Brain Tumor Institute, Northwestern University, Chicago, IL, USA

    Alexander H. Stegh

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  1. Alexander H. Stegh
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Correspondence to Alexander H. Stegh .

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Editors and Affiliations

  1. Dept. Biological Sciences, Kean University, 1000 Moris Avenue, Union, 07083, New Jersey, USA

    M. A. Hayat

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Stegh, A.H. (2011). Cell Death Signaling in Glioblastoma Multiforme: Role of the Bcl2L12 Oncoprotein. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 1. Tumors of the Central Nervous System, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0344-5_16

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  • DOI: https://doi.org/10.1007/978-94-007-0344-5_16

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  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-0343-8

  • Online ISBN: 978-94-007-0344-5

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