ArticleBMC cancer2020
Drug resistance occurred in a newly characterized preclinical model of lung cancer brain metastasis.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Evolutionary Trajectory of Radioresistance in Lung Cancer Brain Metastasis Organoids.Biological procedures online · 2026Article
- Refining Lung Cancer Brain Metastasis Models for Spatiotemporal Dynamic Research and Personalized Therapy.Cancers · 2025Review
- Negative Regulation of Cell Adhesion as a Driver of Brain Metastasis in NSCLC Patients with EGFR Amplification.Biological procedures online · 2025Article
- Dissecting the intratumoral microbiome landscape in lung cancer.Frontiers in immunology · 2025Review
- Approaches to modeling cancer metastasis: from bench to bedside.Frontiers in oncology · 2025Review
- Coordination of anti-CTLA-4 with whole-brain radiation therapy decreases tumor burden during treatment in a novel syngeneic model of lung cancer brain metastasis.Cancer immunology, immunotherapy : CII · 2024Article
- CD146 promotes resistance of NSCLC brain metastases to pemetrexed via the NF-κB signaling pathway.Frontiers in pharmacology · 2024Article
- Immunotherapy: an emerging modality to checkmate brain metastasis.Molecular cancer · 2023Review
- Article
- Development and characterization of a rat brain metastatic tumor model by multiparametric magnetic resonance imaging and histomorphology.Clinical & experimental metastasis · 2022Article
- Towards updated understanding of brain metastasis.American journal of cancer research · 2022Review
- Modulation of the blood-tumor barrier to enhance drug delivery and efficacy for brain metastases.Neuro-oncology advances · 2021Article
- Overcoming the acquired resistance to gefitinib in lung cancer brain metastasis in vitro and in vivo.Archives of toxicology · 2021Article
- The blood-tumour barrier in cancer biology and therapy.Nature reviews. Clinical oncology · 2021Review
- Orthotopic model of lung cancer: isolation of bone micro-metastases after tumor escape from Osimertinib treatment.BMC cancer · 2021Article
- Emodin enhances cisplatin sensitivity in non-small cell lung cancer through Pgp downregulation.Oncology letters · 2021Article
- SEZ6L2 Is an Important Regulator of Drug-Resistant Cells and Tumor Spheroid Cells in Lung Adenocarcinoma.Biomedicines · 2020Article
- Proteomic Reveals Reasons for Acquired Drug Resistance in Lung Cancer Derived Brain Metastasis Based on a Newly Established Multi-Organ Microfluidic Chip Model.Frontiers in bioengineering and biotechnology · 2020Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCancer metastasis and drug resistance have traditionally been studied separately, though these two lethal pathological phenomena almost always occur concurrently. Brain metastasis occurs in a large proportion of lung cancer patients (~ 30%). Once diagnosed, patients have a poor prognosis surviving typically less than 1 year due to lack of treatment efficacy.
methodsHuman metastatic lung cancer cells (PC-9-Br) were injected into the left cardiac ventricle of female athymic nude mice. Brain lesions were allowed to grow for 21 days, animals were then randomized into treatment groups and treated until presentation of neurological symptoms or when moribund. Prior to tissue collection mice were injected with Oregon Green and
resultsA PC-9 brain seeking line (PC-9-Br) was established. Mice inoculated with PC-9-Br resulted in a decreased survival time compared with mice inoculated with parental PC-9. Non-targeted chemotherapy with cisplatin and etoposide (51.5 days) significantly prolonged survival of PC-9-Br brain metastases in mice compared to vehicle control (42 days) or cisplatin and pemetrexed (45 days). Further in-vivo imaging showed greater tumor vasculature in mice treated with cisplatin and etoposide compared to non-tumor regions, which was not observed in mice treated with vehicle or cisplatin and pemetrexed. More importantly, PC-9-Br showed significant resistance to gefitinib by in-vitro MTT assays (IC50 > 2.5 μM at 48 h and 0.1 μM at 72 h) compared with parental PC-9 (IC50: 0.75 μM at 48 h and 0.027 μM at 72 h). Further studies on the molecular mechanisms of gefitinib resistance revealed that EGFR and phospho-EGFR were significantly decreased in PC-9-Br compared with PC-9. Expression of E-cadherin and vimentin did not show EMT in PC-9-Br compared with parental PC-9, and PC-9-Br had neither a T790M mutation nor amplifications of MET and HER2 compared with parental PC-9.
conclusionOur study demonstrated that brain metastases of lung cancer cells may independently prompt drug resistance without drug treatment.
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