The discovery of a potent and selective third-generation EGFR kinase inhibitor as a therapy for EGFR L858R/T790M double mutant non-small cell lung cancer

An, Baijiao; Pan, Tingting; Hu, Jinhui; Pang, Yanqing; Huang, Ling; Chan, Albert S. C.; Li, Xingshu; Yan, Jun

doi:10.1016/j.ejmech.2019.111709

Cited by 17 publications

(11 citation statements)

References 27 publications

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“…20 Although great progresses have been made in past years, 5-year overall survival for NSCLC remains unsatisfactory. 21 Identifying strategies for improving survival is thus necessary. Targeted therapy has been identified as an effective strategy with potential efficacy against lung cancer.…”

Section: Discussionmentioning

confidence: 99%

CEACAM5 stimulates the progression of non-small-cell lung cancer by promoting cell proliferation and migration

et al. 2020

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Objective To detect the expression of CEA-related cell adhesion molecule 5 (CEACAM5) in non-small-cell lung cancer (NSCLC) and explore its function in the progression and development of NSCLC. Methods qRT-PCR and immunohistochemistry were performed to detect CEACAM5 expression in human NSCLC tissues and cell lines. The correlation between CEACAM5 expression and the clinicopathological features of patients with NSCLC was also investigated. MTT, colony formation, wound healing, and immunoblot assays were performed to detect the functions of CEACAM5 in NSCLC cells in vitro, and immunoblotting was used to detect the effects of CEACAM5 on p38–Smad2/3 signaling. Results CEACAM5 expression was elevated in human NSCLC tissues and cells. We further found that CEACAM expression was correlated with clinicopathological features including T division, lymph invasion, and histological grade in patients with NSCLC. The in vitro assays confirmed that CEACAM5 depletion inhibited the proliferation and migration of NSCLC cells by activating p38–Smad2/3 signaling. We verified the involvement of CEACAM5 in the suppression of NSCLC tumor growth in mice. Conclusion CEACAM5 stimulated the progression of NSCLC by promoting cell proliferation and migration in vitro and in vivo. CEACAM5 may serve as a potential therapeutic target for the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

CEACAM5 stimulates the progression of non-small-cell lung cancer by promoting cell proliferation and migration

et al. 2020

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“…B1 † for example). Given that these cell lines have distinct molecular characteristics (HCC827 with EGFR deletion & amplication; NCI-H3255 with EGFR L858R; and NCI-H1975 with EGFR T790M and L858R respectively 15,33,34 ), these observations suggest that the method may also be used to sort/ differentiate cells according to their molecular characteristics and hence provide clues for the design of proper drug/gene treatment strategies. 35,36 Finally, it is worth noting that the characteristic time corresponding to the frequency peaks identied here is $2-15 minutes, similar to that for vimentin remodeling 37 and the formation of integrin-based cell-matrix adhesion.…”

Section: Discussionmentioning

confidence: 99%

Detection of the mesenchymal-to-epithelial transition of invasive non-small cell lung cancer cells by their membrane undulation spectra

Hui

Shao

et al. 2020

RSC Adv.

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“…The Epidermal Growth Factor family (EGFR) is a transmembrane protein that plays a critical role in cell proliferation, survival, migration, adhesion, and differentiation [ 1 ]. Unfortunately, overexpression of the EGFR gene initiates diverse downstream signaling pathways, resulting in cancer aggressiveness and invasiveness [ 2 ]. Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality and morbidity globally, accounting for about 80–90% of all lung malignancies [ 2 , 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, overexpression of the EGFR gene initiates diverse downstream signaling pathways, resulting in cancer aggressiveness and invasiveness [ 2 ]. Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality and morbidity globally, accounting for about 80–90% of all lung malignancies [ 2 , 3 , 4 , 5 ]. EGFR overexpression and mutation (L858R and T790M) is highly prevalent in NSCLC [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of New Hydantoin Acetanilide Derivatives as Anti-NSCLC Targeting EGFRL858R/T790M Mutations

et al. 2022

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Epidermal Growth Factor Receptor (EGFR), its wild type and mutations L858R/T790M, is overexpressed in non-small cell lung cancer (NSCLC) patients and is considered an inevitable oncology target. However, while the potential EGFR inhibitors have been represented in the literature, their cellular activity failed to establish broad potency against EGFR and its mutations. This study identifies a new series of EGFRL858R/T790M inhibitors bearing hydantoin acetanilides. Most compounds revealed strong antiproliferative activity in a range of NSCL cancer models (A549, H1975, and PC9), in which 5a and 5f were the most potent. Compounds 5a and 5f possessed potent anticancer activity on H1975 cells with IC50 values of 1.94 and 1.38 µM, respectively, compared to 9.70 µM for erlotinib. Favorably, 5a and 5f showed low activity on WI-38 normal cells. Western blotting and an EGFR kinase assay test proved the significant EGFR inhibitory activity of 5a. Besides, active hydantoin derivative 5a strongly arrested the cell cycle at the sub G1 and S phases and triggered apoptosis in A549 cells. These results imply that 5a could be considered a promising lead compound for additional development as a potential active agent for anticancer therapy.

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The discovery of a potent and selective third-generation EGFR kinase inhibitor as a therapy for EGFR L858R/T790M double mutant non-small cell lung cancer

Cited by 17 publications

References 27 publications

CEACAM5 stimulates the progression of non-small-cell lung cancer by promoting cell proliferation and migration

CEACAM5 stimulates the progression of non-small-cell lung cancer by promoting cell proliferation and migration

Detection of the mesenchymal-to-epithelial transition of invasive non-small cell lung cancer cells by their membrane undulation spectra

Design and Synthesis of New Hydantoin Acetanilide Derivatives as Anti-NSCLC Targeting EGFRL858R/T790M Mutations

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