ArticleJournal of neuro-oncology2008
Lovastatin enhances gefitinib activity in glioblastoma cells irrespective of EGFRvIII and PTEN status.
Article in Journal of neuro-oncology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
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
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Pooled it
- The role of statins in neurosurgery.Neurosurgical review · 2010Pooled it
- Article
- Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance.Antibiotics (Basel, Switzerland) · 2023Review
- Review
- The multifaceted NF-kB: are there still prospects of its inhibition for clinical intervention in pediatric central nervous system tumors?Cellular and molecular life sciences : CMLS · 2021Review
- Pitavastatin Is a Highly Potent Inhibitor of T-Cell Proliferation.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Pleiotropic effects of statins: A focus on cancer.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Lovastatin-mediated MCF-7 cancer cell death involves LKB1-AMPK-p38MAPK-p53-survivin signalling cascade.Journal of cellular and molecular medicine · 2020Article
- The oncogenic roles of 27-hydroxycholesterol in glioblastoma.Oncology letters · 2019Article
- Circulating MACC1 Transcripts in Glioblastoma Patients Predict Prognosis and Treatment Response.Cancers · 2019Article
- A New Method for Ethical and Efficient Evidence Generation for Off-Label Medication Use in Oncology (A Case Study in Glioblastoma).Frontiers in pharmacology · 2019Article
- Lovastatin causes FaDu hypopharyngeal carcinoma cell death via AMPK-p63-survivin signaling cascade.Scientific reports · 2016Article
- Repurposing some older drugs that cross the blood-brain barrier and have potential anticancer activity to provide new treatment options for glioblastoma.British journal of clinical pharmacology · 2016Review
- Genetic biomarkers of drug response for small-molecule therapeutics targeting the RTK/Ras/PI3K, p53 or Rb pathway in glioblastoma.CNS oncology · 2016Review
- Additive Anti-Tumor Effects of Lovastatin and Everolimus In Vitro through Simultaneous Inhibition of Signaling Pathways.PloS one · 2015Article
- Molecular mechanisms of fenofibrate-induced metabolic catastrophe and glioblastoma cell death.Molecular and cellular biology · 2015Article
- Combination of 13-Cis retinoic acid and lovastatin: marked antitumor potential in vivo in a pheochromocytoma allograft model in female athymic nude mice.Endocrinology · 2014Article
- Atorvastatin overcomes gefitinib resistance in KRAS mutant human non-small cell lung carcinoma cells.Cell death & disease · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epidermal growth factor receptor (EGFR) is commonly amplified and mutated in glioblastoma, making it a compelling therapeutic target. Recent reports have demonstrated clinical activity of the EGFR inhibitors gefitinib and erlotinib in a subset of glioblastoma patients. Co-expression of EGFRvIII, a constitutively active mutant receptor expressed in 50% of tumours, and PTEN, an inhibitor of PI3K activity, by glioblastoma cells is associated with clinical response to these EGFR kinase inhibitors. PTEN loss and resulting increased PI3K pathway activity appears to act as a resistance factor. A critical therapeutic challenge is to identify agents that enhance the anti-cancer effects of these agents and promote responsiveness to EGFR kinase inhibitors in a broader spectrum of glioblastoma patients. For example, combining gefitinib with inhibitors of the PI3K/AKT pathway show enhanced cytotoxicity in glioblastoma derived cell lines. Here, we show that targeting HMG-CoA reductase with lovastatin, that can affect the activity of multiple cell signaling pathways, significantly enhanced the sensitivity of glioblastoma cells to the EGFR kinase inhibitor gefitinib in the five cell lines tested. In an isogenic model system, U87MG glioblastoma cells expressing EGFRvIII and PTEN in relevant combinations, we show that combined gefitinib and lovastatin treatments induce potent synergistic cytotoxicity irrespective of EGFRvIII and PTEN status. These studies demonstrate the potential of lovastatin to augment the cytotoxic effects of gefitinib and provide a rationale for combined statin/EGFR targeted therapies in glioblastoma patients.
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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.