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Citations to this article

Resistance of human glioblastoma multiforme cells to growth factor inhibitors is overcome by blockade of inhibitor of apoptosis proteins
David S. Ziegler, … , Leigh Zawel, Andrew L. Kung
David S. Ziegler, … , Leigh Zawel, Andrew L. Kung
Published August 1, 2008
Citation Information: J Clin Invest. 2008;118(9):3109-3122. https://doi.org/10.1172/JCI34120.
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Research Article Oncology Article has an altmetric score of 3

Resistance of human glioblastoma multiforme cells to growth factor inhibitors is overcome by blockade of inhibitor of apoptosis proteins

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Abstract

Multiple receptor tyrosine kinases (RTKs), including PDGFR, have been validated as therapeutic targets in glioblastoma multiforme (GBM), yet inhibitors of RTKs have had limited clinical success. As various antiapoptotic mechanisms render GBM cells resistant to chemo- and radiotherapy, we hypothesized that these antiapoptotic mechanisms also confer resistance to RTK inhibition. We found that in vitro inhibition of PDGFR in human GBM cells initiated the intrinsic pathway of apoptosis, as evidenced by mitochondrial outer membrane permeabilization, but downstream caspase activation was blocked by inhibitor of apoptosis proteins (IAPs). Consistent with this, inhibition of PDGFR combined with small molecule inactivation of IAPs induced apoptosis in human GBM cells in vitro and had synergistic antitumor effects in orthotopic mouse models of GBM and in primary human GBM neurospheres. These results demonstrate that concomitant inhibition of IAPs can overcome resistance to RTK inhibitors in human malignant GBM cells, and suggest that blockade of IAPs has the potential to improve treatment outcomes in patients with GBM.

Authors

David S. Ziegler, Renee D. Wright, Santosh Kesari, Madeleine E. Lemieux, Mary A. Tran, Monish Jain, Leigh Zawel, Andrew L. Kung

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Total citations by year

Year: 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 Total
Citations: 3 4 1 4 7 5 2 3 6 6 6 1 3 51
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Citations to this article in year 2015 (2)

Title and authors Publication Year
USP11-dependent selective cIAP2 deubiquitylation and stabilization determine sensitivity to Smac mimetics
EW Lee, D Seong, J Seo, M Jeong, HK Lee, J Song
Cell Death and Differentiation 2015
How to train glioma cells to die: molecular challenges in cell death
J Wojton, WH Meisen, B Kaur
Journal of Neuro-Oncology 2015

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Referenced in 13 patents
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