ArticleBosnian journal of basic medical sciences2021
Alectinib and lorlatinib function by modulating EMT-related proteins and MMPs in NSCLC metastasis.
Article in Bosnian journal of basic medical sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Comparison of the efficacy based on clinicopathological characteristics and the safety of first-line treatments for patients with advanced ALK rearrangement non-small cell lung cancer: a network meta-analysis.Frontiers in oncology · 2025Pooled it
- [Analysis of Risk Factors for Meningeal Metastasis in Patients with Lung Adenocarcinoma Following Non-surgical Interventions].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- Article
- High expression of COL8A1 predicts poor prognosis and promotes EMT in papillary thyroid cancer.Endocrine connections · 2024Article
- [Aumolertinib combined with anlotinib inhibits proliferation of non-small cell lung cancer cells by down-regulating the PI3K/AKT pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Appendicitis while on alectinib for non-small cell lung cancer: a tale of two case reports.Frontiers in oncology · 2024Article
- Cerebrospinal fluid exosomal protein alterations via proteomic analysis of NSCLC with leptomeningeal carcinomatosis.Journal of neuro-oncology · 2023Article
- Heterogeneity and plasticity of epithelial-mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms.Cell proliferation · 2023Review
- Micro-ribonucleic acids (miRNAs) and a proteomic profile in lung adenocarcinoma cases with brain metastasis.Annals of translational medicine · 2022Article
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2 authors at 1 institution in 1 country.
Funding
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Abstract
Most advanced non-small cell lung cancer (NSCLC) patients are accompanied by brain metastasis which is the major cause of increased mortality. The fusion rearrangement of anaplastic lymphoma kinase (ALK) gene is an important feature of brain metastasis in lung cancer. The novel ALK inhibitors alectinib and lorlatinib are shown to be effective against NSCLC brain metastasis, while their underlying mechanism of action is unclear. Epithelial-mesenchymal transition (EMT) proteins and matrix metalloproteinases (MMPs) play important roles in brain metastasis by regulating the blood-brain barrier (BBB). To reveal the molecular function of alectinib and lorlatinib, we explored their effects on the cellular levels of EMT markers: VIM and FN1 and the matrix metalloproteinases MMP-9 and MMP-7. The mRNA and protein levels of VIM, FN1, MMP-9, and MMP-7 were elevated in H3122 cells. However, upon alectinib and lorlatinib treatment, the levels were significantly reduced. Similar results were obtained when these experiments were performed either in a dose-dependent or time-dependent manner. Furthermore, alectinib and lorlatinib also inhibited the cell viability and migration of H3122 cells. Interestingly, in comparison to individual drugs, the combination of alectinib and lorlatinib was found to be substantially more effective. Overall, these results suggest that alectinib and lorlatinib possibly function through the downregulation of MMPs and EMT in NSCLC metastasis.
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