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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
Citation information
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Citations to this article in year 2013 (6)

Title and authors Publication Year
Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma
N Syed, J Langer, K Janczar, P Singh, CL Nigro, L Lattanzio, HM Coley, E Hatzimichael, J Bomalaski, P Szlosarek, M Awad, K O'Neil, F Roncaroli, T Crook
Cell Death and Disease 2013
Inhibitor of Apoptosis Proteins: Promising Targets for Cancer Therapy
TW Owens
Journal of Carcinogenesis & Mutagenesis 2013
Anti-cancer IAP antagonists promote bone metastasis: a cautionary tale
C Yang, DV Novack
Journal of Bone and Mineral Metabolism 2013
Simultaneous Reconstruction of Multiple Signaling Pathways via the Prize-Collecting Steiner Forest Problem
N Tuncbag, A Braunstein, A Pagnani, SS Huang, J Chayes, C Borgs, R Zecchina, E Fraenkel
Journal of Computational Biology 2013
Current Understanding on EGFR and Wnt/β-Catenin Signaling in Glioma and Their Possible Crosstalk
I Paul, S Bhattacharya, A Chatterjee, MK Ghosh
Genes & cancer 2013
Apoptosis repressor with caspase recruitment domain is regulated by MAPK/PI3K and confers drug resistance and survival advantage to AML
PY Mak, DH Mak, H Mu, Y Shi, P Ruvolo, V Ruvolo, R Jacamo, JK Burks, W Wei, X Huang, SM Kornblau, M Andreeff, BZ Carter
Apoptosis 2013

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