ArticleJournal of cancer research and clinical oncology2014
Hsp90 inhibition enhances PI-3 kinase inhibition and radiosensitivity in glioblastoma.
Article in Journal of cancer research and clinical oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- PI3K/AKT/mTOR Targeting in Colorectal Cancer Radiotherapy: A Systematic Review.Journal of gastrointestinal cancer · 2025Pooled it
- Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II).Journal of neuro-oncology · 2019Trial
- Review
- The function of chaperones in the radioresistance of glioblastoma: a new insight into the current knowledge.Brain tumor pathology · 2025Review
- Gedunin modulates cellular growth and apoptosis in glioblastoma cell lines.Cancer reports (Hoboken, N.J.) · 2024Article
- Heat shock protein paradigms in cancer progression: future therapeutic perspectives.3 Biotech · 2024Review
- Natural Products Targeting Hsp90 for a Concurrent Strategy in Glioblastoma and Neurodegeneration.Metabolites · 2022Review
- Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials.Cancers · 2022Review
- Small Molecule Inhibitors in Adult High-Grade Glioma: From the Past to the Future.Frontiers in oncology · 2022Review
- The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells.Scientific reports · 2020Article
- Improving the Efficacy of Tumor Radiosensitization Through Combined Molecular Targeting.Frontiers in oncology · 2020Review
- Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?International journal of molecular sciences · 2019Review
- PIK3CA missense mutations promote glioblastoma pathogenesis, but do not enhance targeted PI3K inhibition.PloS one · 2018Article
- CISD2 promotes the proliferation of glioma cells via suppressing beclin‑1‑mediated autophagy and is targeted by microRNA‑449a.Molecular medicine reports · 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
- Article
- PI3 Kinase Pathway and MET Inhibition is Efficacious in Malignant Pleural Mesothelioma.Scientific reports · 2016Article
- Chitooligosaccharides promote radiosensitivity in colon cancer line SW480.World journal of gastroenterology · 2016Article
- Advances in HSP27 and HSP90-targeting strategies for glioblastoma.Journal of neuro-oncology · 2016Review
- BKM-120 (Buparlisib): A Phosphatidyl-Inositol-3 Kinase Inhibitor with Anti-Invasive Properties in Glioblastoma.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCombined targeting with a PI3-kinase inhibitor, BKM120, and an Hsp90 inhibitor, HSP990, was investigated as a multi-targeted approach to potentiate cell death in glioblastoma (GBM). Additionally, the effect of dual drug treatment combined with cytotoxic stress (radiation therapy) was examined.
methodsFour human GBM cell lines containing wild-type or mutated PTEN and/or p53 were studied. The effects of drug treatments on cell viability, apoptosis induction, pAKt activity, cell cycle arrest, clonogenicity, and tumor growth delay were studied.
resultsCombined concurrent treatment with both drugs produced more cell killing in cell viability and apoptosis assays than either drug alone. BKM120 plus HSP990 induced suppression of baseline Akt signaling as well as radiation (RT)-induced pAkt signaling in all cell lines. Cell cycle analysis revealed that HSP990 and BKM120, singly or combined, induced G2/M arrest leading to apoptosis/necrosis and polyploidy. Additionally, the drugs radiosensitized GBM cells in clonogenic assays. In vivo tumor growth delay studies demonstrated the effectiveness of combined drug treatment with HSP990 and BKM120 over single drug treatment, as well as the effectiveness of combined drug treatment in enhancing the effectiveness of radiation therapy.
conclusionsIn conclusion, HSP990 and BKM120, with and without RT, are active agents against glioma tumors. The sensitivity to these agents does not appear to depend on PTEN/p53status in the cell lines tested. We suggest that the combined action of both drugs is a viable multi-targeted strategy with the potential to improve clinical outcome for patients with high-grade glioma.
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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.