Dataset Information

[Research Progresses in the Treatment of NSCLC with MET Gene Variants: A Riview].

ABSTRACT: Mesenchymal-epithelial transition factor (MET) has long been considered as the most crucial and promising driver gene in the occurrence and development of non-small cell lung cancer (NSCLC), except for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and c-ROS oncogene 1 receptor tyrosine kinase (ROS1). In recent years, therapeutic drugs targeting MET have been continuously developed and applied in clinical practice. First, the curative effect of NSCLC patients with MET exon 14 skipping mutations has been further improved. In addition, when MET amplification occurs after resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced EGFR-mutant NSCLC, the combination of MET-TKIs and EGFR-TKIs has brought significant survival benefits and many other advances. This article reviews the treatment progress of NSCLC patients with different types of MET variants under different circumstances, which provides reference for the selection of clinical treatment strategies. .

SUBMITTER: Chen R

PROVIDER: S-EPMC9845091 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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[Research Progresses in the Treatment of NSCLC with MET Gene Variants: A Riview].

Chen Ran R Jiang Chang C Tang Jun J Ma Li L Zhang Shucai S

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20221201 12

Mesenchymal-epithelial transition factor (MET) has long been considered as the most crucial and promising driver gene in the occurrence and development of non-small cell lung cancer (NSCLC), except for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and c-ROS oncogene 1 receptor tyrosine kinase (ROS1). In recent years, therapeutic drugs targeting MET have been continuously developed and applied in clinical practice. First, the curative effect of NSCLC patients with MET ...[more]

PMID: 36617474

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Project description:Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer. Human non small cell lung cancers (NSCLC) with activating mutations in the EGFR gene frequently experience significant tumor regression when treated with EGFR tyrosine kinase inhibitors (TKIs), although acquired resistance invariably develops. Resistance to TKI treatments has been associated to secondary mutations in the EGFR gene or to activation of additional bypass signaling pathways including the ones mediated by receptor tyrosine kinases, Fas receptor and NF-kB. In more than 30-40% of cases, however, the mechanisms underpinning drug-resistance are still unknown. The establishment of cellular and mouse models can facilitate the unveiling of mechanisms leading to drug-resistance and the development or validation of novel therapeutic strategies aimed at overcoming resistance and enhancing outcomes in NSCLC patients. Here we describe the establishment and characterization of EGFR TKI-resistant NSCLC cell lines and a pilot study on the effects of a combined MET and EGFR inhibitors treatment. The characterization of the erlotinib-resistant cell lines confirmed the association of EGFR TKI resistance with loss of EGFR gene amplification and/or AXL overexpression and/or MET gene amplification and MET receptor activation. These cellular models can be instrumental to further investigate the signaling pathways associated to EGFR TKI-resistance. Finally the drugs combination pilot study shows that MET gene amplification and MET receptor activation are not sufficient to predict a positive response of NSCLC cells to a cocktail of MET and EGFR inhibitors and highlights the importance of identifying more reliable biomarkers to predict the efficacy of treatments in NSCLC patients resistant to EGFR TKI.

Dataset Information

[Research Progresses in the Treatment of NSCLC with MET Gene Variants: A Riview].

Publications

[Research Progresses in the Treatment of NSCLC with MET Gene Variants: A Riview].

Similar Datasets

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