scholarly journals Tumor immune microenvironment in non-small cell lung cancer with EGFR mutation before and after EGFR-TKIs treatment

2021 ◽  
Author(s):  
chao wang ◽  
lihui liu ◽  
sini li ◽  
hua bai ◽  
jie wang
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Treatment Time ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Before And After ◽  
Almost All ◽  
Egfr Tkis

Lung cancer is the most common cancer and a leading cause of death from cancer in men and women in the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are considered as the first-line treatment of EGFR mutated NSCLC. However, almost all patients eventually develop acquired resistance to EGFR-TKIs, with a median PFS of 9-14 months. With the development of immunotherapy, people realize that the interaction between tumor immune microenvironment (TIME) and tumor cells can also affect EGFR-TKIs treatment. TIME contains a variety of elements and previous researches of TIME in EGFR-TKIs therapy on NSCLC are decentralized. Here, we review the characteristics of TIME in NSCLC from EGFR-TKIs therapy and its role in TKIs resistance.

scholarly journals Mechanisms of Resistance to EGFR TKIs and Development of a New Generation of Drugs in Non-Small-Cell Lung Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Takayuki Kosaka ◽  
Ei Yamaki ◽  
Akira Mogi ◽  
Hiroyuki Kuwano
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Clinical Problem ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Tkis

Gefitinib and erlotinib, which are epidermal growth factor receptor- (EGFR-) specific tyrosine kinase inhibitors (TKIs), are widely used as molecularly targeted drugs for non-small-cell lung cancer (NSCLC). Currently, the search forEGFRgene mutations is becoming essential for the treatment of NSCLC since these have been identified as predictive factors for drug sensitivity. On the other hand, in almost all patients responsive to EGFR-TKIs, acquired resistance is a major clinical problem. Mechanisms of acquired resistance reported in the past few years include secondary mutation of theEGFRgene, amplification of theMETgene, and overexpression of HGF; novel pharmaceutical agents are currently being developed to overcome resistance. This review focuses on these mechanisms of acquired resistance to EGFR-TKIs and discusses how they can be overcome.

scholarly journals Mechanism of Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors and a Potential Treatment Strategy

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 212 ◽  
Author(s):  
Tatsuya Nagano ◽  
Motoko Tachihara ◽  
Yoshihiro Nishimura
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
T790m Mutation ◽  
Epidermal Growth ◽  
Egfr Mutated ◽  
Egfr Tki ◽  
Egfr Tkis

Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) improves the overall survival of patients with EGFR-mutated non-small-cell lung cancer (NSCLC). First-generation EGFR-TKIs (e.g., gefitinib and erlotinib) or second-generation EGFR-TKIs (e.g., afatinib and dacomitinib) are effective for the treatment of EGFR-mutated NSCLC, especially in patients with EGFR exon 19 deletions or an exon 21 L858R mutation. However, almost all cases experience disease recurrence after 1 to 2 years due to acquired resistance. The EGFR T790M mutation in exon 20 is the most frequent alteration associated with the development of acquired resistance. Osimertinib—a third-generation EGFR-TKI—targets the T790M mutation and has demonstrated high efficacy against EGFR-mutated lung cancer. However, the development of acquired resistance to third-generation EGFR-TKI, involving the cysteine residue at codon 797 mutation, has been observed. Other mechanisms of acquired resistance include the activation of alternative pathways or downstream targets and histological transformation (i.e., epithelial–mesenchymal transition or conversion to small-cell lung cancer). Furthermore, the development of primary resistance through overexpression of the hepatocyte growth factor and suppression of Bcl-2-like protein 11 expression may lead to problems. In this report, we review these mechanisms and discuss therapeutic strategies to overcome resistance to EGFR-TKIs.

Chitosan-derived Nanoparticles Impede Signal Transduction for T790M Lung Cancer Therapy

2021 ◽  
Author(s):  
Guojun Huang ◽  
Qi Chen ◽  
Jiawei Hu ◽  
Jianming Mao ◽  
Yunhong He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
T790m Mutation ◽  
Develop Disease Progression ◽  
Lung Cancer Therapy ◽  
Epidermal Growth ◽  
Egfr Tkis ◽  
Receptor Tyrosine Kinase Inhibitors

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treated patients ultimately develop disease progression, about 50% of which involved in the emergence of a T790M mutation acquiring drug resistance. In...

Effect of loss of a chromosome 7 containing multiple copies of EGFR gene on acquired resistance to EGFR-TKIs in EGFR mutated NSCLC.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18091-e18091
Author(s):  
Koh Furugaki ◽  
Toshiki Iwai ◽  
Yoichiro Moriya ◽  
Kaori Fujimoto-Ouchi
Keyword(s):  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Chromosome 7 ◽  
Fish Analysis ◽  
High Concentration ◽  
Multiple Copies ◽  
Egfr Mutated ◽  
Egfr Tkis ◽  
Resistant Cells

e18091 Background: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show notable effects for non-small cell lung cancers (NSCLC) harboring EGFR activating mutations. However, almost all patients eventually acquire resistance to EGFR-TKIs within several years. The major mechanisms of acquired resistance are acquisition of a secondary EGFR mutation T790M and amplification of MET. However, the mechanisms of other resistance remain unclear. In this study, we established novel erlotinib-resistant NSCLC cells and examined their resistant mechanism. Methods: Resistant cells were established by continuously exposing EGFR mutated NSCLC cells HCC827 to 0.1, 1 or 10 μM of erlotinib in 96 well plates for three months. The resistant mechanisms were determined by direct sequence analysis and EGFR FISH analysis. Results: Resistant cells were emerged from 14/96 and 3/96 wells by 0.1 μM and 1 μM of erlotinib exposure, respectively. No resistant cells appeared in the wells of 10 μM of erlotinib. The IC50 values of these resistant cells were more than 100-fold higher than that of parental cells. No secondary mutation of T790M was detected in any of the resistant cells. Instead, we found that 13/17 resistant cells were dominated by EGFR not amplified cells and one of resistant cells B10 consisted of more than 99.9% of them, while the parental cells consisted of 2.5% of EGFR not amplified cells. Then, we isolated EGFR not amplified clone 4D8 from parental cells and found that this clone also had a resistance to erlotinib comparable to the resistant cells B10. Metaphase FISH analysis showed that EGFR amplified cells in parental cells had a chromosome 7 containing multiple copies of EGFR, while EGFR not amplified cells in B10 did not have it. Furthermore, we found that EGFR not amplified cells were constantly emerged from EGFR amplified clone isolated from parental cells under normal cell culture condition. Conclusions: Loss of a chromosome 7 containing multiple copies of EGFR causes acquired resistance in HCC827 cells when exposed to relatively low concentration of erlotinib, while high concentration of erlotinib deprives HCC827 cells of the chance of emergence of resistant cells.

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