ArticleFASEB bioAdvances2020
Lung cancer cells survive epidermal growth factor receptor tyrosine kinase inhibitor exposure through upregulation of cholesterol synthesis.
Article in FASEB bioAdvances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
17 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Proteomic Analysis Highlights the Impact of the Sphingolipid Metabolizing Enzyme β-Galactosylceramidase on Mitochondrial Plasticity in Human Melanoma.International journal of molecular sciences · 2024Article
- EGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth.Cancer discovery · 2024Article
- EGFR TKI resistance in lung cancer cells using RNA sequencing and analytical bioinformatics tools.Journal of biomolecular structure & dynamics · 2023Article
- How Neuromembrane Lipids Modulate Membrane Proteins: Insights from G-Protein-Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs).Cold Spring Harbor perspectives in biology · 2023Review
- Role of Cannabidiol for Improvement of the Quality of Life in Cancer Patients: Potential and Challenges.International journal of molecular sciences · 2022Review
- Inhibition of epidermal growth factor receptor suppresses parathyroid hormone-related protein expression in tumours and ameliorates cancer-associated cachexia.Journal of cachexia, sarcopenia and muscle · 2022Article
- Pretreatment HDL-C and ApoA1 are predictive biomarkers of progression-free survival in patients with EGFR mutated advanced non-small cell lung cancer treated with TKI.Thoracic cancer · 2022Article
- A Transcriptomic Approach to Elucidate the Mechanisms of Gefitinib-Induced Toxicity in Healthy Human Intestinal Organoids.International journal of molecular sciences · 2022Article
- Review
- Enzymes in the Cholesterol Synthesis Pathway: Interactomics in the Cancer Context.Biomedicines · 2021Article
- Review
- High Circulating Sonic Hedgehog Protein Is Associated With Poor Outcome in EGFR-Mutated Advanced NSCLC Treated With Tyrosine Kinase Inhibitors.Frontiers in oncology · 2021Article
- DPP4 Regulates DHCR24-Mediated Cholesterol Biosynthesis to Promote Methotrexate Resistance in Gestational Trophoblastic Neoplastic Cells.Frontiers in oncology · 2021Article
- Mechanistic Insights Delineating the Role of Cholesterol in Epithelial Mesenchymal Transition and Drug Resistance in Cancer.Frontiers in cell and developmental biology · 2021Review
- Roles of Farnesyl-Diphosphate Farnesyltransferase 1 in Tumour and Tumour Microenvironments.Cells · 2020Review
- Lung cancer cells survive epidermal growth factor receptor tyrosine kinase inhibitor exposure through upregulation of cholesterol synthesis.FASEB bioAdvances · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide clinical benefits over chemotherapy for lung cancer patients with EGFR activating mutations. Despite initial clinical responses, long-term efficacy is not possible because of acquired resistance to these therapies. We have developed EGFR TKI drug-tolerant (DT) human lung cancer cell lines as a model for de novo resistance. Mass spectroscopic analysis revealed that the cytochrome P450 protein, CYP51A1 (Lanosterol 14α-demethylase), which is directly involved with cholesterol synthesis, was significantly upregulated in the DT cells. Total cellular cholesterol, and more specifically, mitochondrial cholesterol, were found to be upregulated in DT cells. We then used the CYP51A1 inhibitor, ketoconazole, to downregulate cholesterol synthesis. In both parental and DT cells, ketoconazole and EGFR TKIs acted synergistically to induce apoptosis and overcome the development of EGFR tolerance. Lastly, this combination therapy was shown to shrink the growth of tumors in an in vivo mouse model of EGFR TKI resistance. Thus, our study demonstrates for the first time that ketoconazole treatment inhibits upregulation of mitochondrial cholesterol and thereby overcomes EGFR-TKI resistance in lung cancer cells.
Indexed as
Identifiers
What OpenQuestion holds
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.