ArticleThe Journal of clinical investigation2008
Resistance of human glioblastoma multiforme cells to growth factor inhibitors is overcome by blockade of inhibitor of apoptosis proteins.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 101 citations in OpenAlex.
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- Comparative analysis of metabolome and transcriptomes to explore the inhibited influence of sonodynamic therapy combined with lonidamine on hepatocellular carcinoma.Drug delivery · 2025Article
- Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Copy Number Variation and Rearrangements Assessment in Cancer: Comparison of Droplet Digital PCR with the Current Approaches.International journal of molecular sciences · 2021Review
- Data-Driven Computational Modeling Identifies Determinants of Glioblastoma Response to SHP2 Inhibition.Cancer research · 2021Article
- Article
- Oxidative Stress-Part of the Solution or Part of the Problem in the Hypoxic Environment of a Brain Tumor.Antioxidants (Basel, Switzerland) · 2020Article
- Review
- Receptor tyrosine kinase targeting in glioblastoma: performance, limitations and future approaches.Contemporary oncology (Poznan, Poland) · 2020Review
- Role of apoptosis repressor with caspase recruitment domain (ARC) in cancer.Oncology letters · 2019Review
- TROY interacts with RKIP to promote glioma development.Oncogene · 2019Article
- Insulin-like growth factor 1/insulin-like growth factor 1 receptor signaling protects against cell apoptosis through the PI3K/AKT pathway in glioblastoma cells.Experimental and therapeutic medicine · 2018Article
- Pharmacological Targeting of Cell Cycle, Apoptotic and Cell Adhesion Signaling Pathways Implicated in Chemoresistance of Cancer Cells.International journal of molecular sciences · 2018Review
- Drug Repositioning in Glioblastoma: A Pathway Perspective.Frontiers in pharmacology · 2018Review
- Chromosomal instability induced by increased BIRC5/Survivin levels affects tumorigenicity of glioma cells.BMC cancer · 2017Article
- Survivin a radiogenetic promoter for glioblastoma viral gene therapy independently from CArG motifs.Clinical and translational medicine · 2017Article
- Inhibition of colony stimulating factor-1 receptor abrogates microenvironment-mediated therapeutic resistance in gliomas.Oncogene · 2017Article
- Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Insights into molecular therapy of glioma: current challenges and next generation blueprint.Acta pharmacologica Sinica · 2017Review
- Elucidation of the genetic and epigenetic landscape alterations in RNA binding proteins in glioblastoma.Oncotarget · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.