Abstract
The endoplasmic reticulum (ER) stress response represents a cellular “yin-yang” process, where low to moderate activity is cell protective and supports chemoresistance (yang), but where more severe conditions will aggravate these mechanisms to the point where they abandon their protective efforts and instead turn on a cell death program (yin). Because tumor cells frequently experience chronic stress conditions (due to hypoxia, hypoglycemia, acidification, etc.), the protective yang components of their ER stress response are continuously engaged and thus less able to neutralize additional insults taxing the ER stress response. This tumor-specific situation may provide therapeutic opportunities for pharmacologic intervention, where further aggravation of ER stress would lead to the activation of pro-apoptotic yin components and result in tumor cell death. This review will describe the yin-yang principle of ER stress, and will present pharmacologic agents and combination strategies aimed at exploiting the ER stress response for improved therapeutic outcomes, particularly in the setting of difficult to treat tumor types such as glioblastoma.
Keywords: Endoplasmic reticulum stress, unfolded protein response, celecoxib, dimethyl-celecoxib, nelfinavir, bortezomib, EGCG, angiogenesis, chemoadjuvant, glioma therapy
Current Pharmaceutical Design
Title: Preclinical Development of Novel Anti-Glioma Drugs Targeting the Endoplasmic Reticulum Stress Response
Volume: 17 Issue: 23
Author(s): Axel H. Schonthal, Thomas C. Chen, Florence M. Hofman, Stan G. Louie and Nicos A. Petasis
Affiliation:
Keywords: Endoplasmic reticulum stress, unfolded protein response, celecoxib, dimethyl-celecoxib, nelfinavir, bortezomib, EGCG, angiogenesis, chemoadjuvant, glioma therapy
Abstract: The endoplasmic reticulum (ER) stress response represents a cellular “yin-yang” process, where low to moderate activity is cell protective and supports chemoresistance (yang), but where more severe conditions will aggravate these mechanisms to the point where they abandon their protective efforts and instead turn on a cell death program (yin). Because tumor cells frequently experience chronic stress conditions (due to hypoxia, hypoglycemia, acidification, etc.), the protective yang components of their ER stress response are continuously engaged and thus less able to neutralize additional insults taxing the ER stress response. This tumor-specific situation may provide therapeutic opportunities for pharmacologic intervention, where further aggravation of ER stress would lead to the activation of pro-apoptotic yin components and result in tumor cell death. This review will describe the yin-yang principle of ER stress, and will present pharmacologic agents and combination strategies aimed at exploiting the ER stress response for improved therapeutic outcomes, particularly in the setting of difficult to treat tumor types such as glioblastoma.
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Cite this article as:
H. Schonthal Axel, C. Chen Thomas, M. Hofman Florence, G. Louie Stan and A. Petasis Nicos, Preclinical Development of Novel Anti-Glioma Drugs Targeting the Endoplasmic Reticulum Stress Response, Current Pharmaceutical Design 2011; 17 (23) . https://dx.doi.org/10.2174/138161211797249242
DOI https://dx.doi.org/10.2174/138161211797249242 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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