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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 2011 (6)

Title and authors Publication Year
MicroRNAs and glioblastoma: roles in core signalling pathways and potential clinical implications
J Sana, M Hajduch, J Michalek, R Vyzula, O Slaby
Journal of Cellular and Molecular Medicine 2011
A small-molecule IAP inhibitor overcomes resistance to cytotoxic therapies in malignant gliomas in vitro and in vivo
DS Ziegler, J Keating, S Kesari, EM Fast, L Zawel, N Ramakrishna, J Barnes, MW Kieran, SE van Zanten, AL Kung
Neuro-Oncology 2011
Changes in Caregiver Perceptions Over Time in Response to Providing Care for a Loved One With a Primary Malignant Brain Tumor
A Hricik, H Donovan, SE Bradley, BA Given, CM Bender, A Newberry, R Hamilton, CW Given, P Sherwood
Oncology Nursing Forum 2011
Expression of ARC (apoptosis repressor with caspase recruitment domain), an antiapoptotic protein, is strongly prognostic in AML
BZ Carter, YH Qiu, N Zhang, KR Coombes, DH Mak, DA Thomas, F Ravandi, HM Kantarjian, E Koller, M Andreeff, SM Kornblau
Blood 2011
Usp18 Regulates Epidermal Growth Factor (EGF) Receptor Expression and Cancer Cell Survival via MicroRNA-7*
JE Duex, L Comeau, A Sorkin, B Purow, B Kefas
The Journal of biological chemistry 2011
Apoptosis inhibitor ARC promotes breast tumorigenesis, metastasis, and chemoresistance
CM Medina-Ramirez, S Goswami, T Smirnova, D Bamira, B Benson, N Ferrick, J Segall, JW Pollard, RN Kitsis
Cancer research 2011

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