Uncommon EGFR Mutations in Non-Small Cell Lung Cancer and Their Impact on the Treatment

Bílek, Ondřej; Holánek, Miloš; Berkovcová, Jitka; Horký, Ondřej; Kazda, Tomáš; Čoupková, Helena; Špelda, Stanisla; Kristková, L; Zvaríková, Mária; Podhorec, Ján; Borilova, Simona; Bohovicová, Lucia; Dubská, Lenka Zdražilová

doi:10.14735/amko20193s6

Cited by 5 publications

(5 citation statements)

References 62 publications

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“…The EGFR is one of the most common mutation driver oncogenes. Among Asian female nonsmokers with NSCLC, the mutation rate was as high as 59.4%, with exon 19 deletions and L858R point mutations located in the receptor tyrosine kinase (RTK) domain accounting for 90% of mutations ( Li et al, 2016 ; Bílek et al, 2019 ). The stimulation of MAPK and PI3K is highly associated with increased cancer risk, and the downstream signaling pathways are associated with cell proliferation, metastasis, and drug resistance ( Villaruz et al, 2013 ; Ciuffreda et al, 2014 ).…”

Section: Nanodrug Targeted Epidermal Growth Factor Receptor In Nsclcmentioning

confidence: 99%

Advancement of regulating cellular signaling pathways in NSCLC target therapy via nanodrug

Li,

Huang

et al. 2023

Front. Chem.

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Lung cancer (LC) is one of the leading causes of high cancer-associated mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common type of LC. The mechanisms of NSCLC evolution involve the alterations of multiple complex signaling pathways. Even with advances in biological understanding, early diagnosis, therapy, and mechanisms of drug resistance, many dilemmas still need to face in NSCLC treatments. However, many efforts have been made to explore the pathological changes of tumor cells based on specific molecular signals for drug therapy and targeted delivery. Nano-delivery has great potential in the diagnosis and treatment of tumors. In recent years, many studies have focused on different combinations of drugs and nanoparticles (NPs) to constitute nano-based drug delivery systems (NDDS), which deliver drugs regulating specific molecular signaling pathways in tumor cells, and most of them have positive implications. This review summarized the recent advances of therapeutic targets discovered in signaling pathways in NSCLC as well as the related NDDS, and presented the future prospects and challenges.

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Section: Nanodrug Targeted Epidermal Growth Factor Receptor In Nsclcmentioning

confidence: 99%

Advancement of regulating cellular signaling pathways in NSCLC target therapy via nanodrug

Li,

Huang

et al. 2023

Front. Chem.

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“…The EGFR-activating gene mutations in exons 18, 19, 20, and 21 are classically divided into common (exon 19 deletion, exon 21 L858R point mutation), which correspond to 85–90% and generally confer sensitivity to EGFR-TKIs treatment, and uncommon (rare EGFR mutations and complex EGFR mutations), which account for 10–15% and present variable predictive values, from sensitivity to resistance [ 4 , 8 ]. Moreover, it is also possible to find other EGFR alterations consisting of the combination of EGFR mutations with other EGFR mutations or with one or more mutations of other genes (tumour suppressor gene or oncogene).…”

Section: Introductionmentioning

confidence: 99%

“…In some cases, only a small percentage of tumour cells has the specific EGFR mutation. The variable sensitivities to EGFR-TKIs could be explained by the variable tertiary structure of the EGFR protein under the influence of the different EGFR mutations [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

The Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: From Molecular Mechanisms to Clinical Application of New Therapeutic Strategies

Laface¹,

Maselli²,

Santoro³

et al. 2023

Pharmaceutics

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Almost 17% of Western patients affected by non-small cell lung cancer (NSCLC) have an activating epidermal growth factor receptor (EGFR) gene mutation. Del19 and L858R are the most-common ones; they are positive predictive factors for EGFR tyrosine kinase inhibitors (TKIs). Currently, osimertinib, a third-generation TKI, is the standard first-line therapy for advanced NSCLC patients with common EGFR mutations. This drug is also administered as a second-line treatment for those patients with the T790M EGFR mutation and previously treated with first- (erlotinib, gefitinib) or second- (afatinib) generation TKIs. However, despite the high clinical efficacy, the prognosis remains severe due to intrinsic or acquired resistance to EGRF-TKIs. Various mechanisms of resistance have been reported including the activation of other signalling pathways, the development of secondary mutations, the alteration of the downstream pathways, and phenotypic transformation. However, further data are needed to achieve the goal of overcoming resistance to EGFR-TKIs, hence the necessity of discovering novel genetic targets and developing new-generation drugs. This review aimed to deepen the knowledge of intrinsic and acquired molecular mechanisms of resistance to EGFR-TKIs and the development of new therapeutic strategies to overcome TKIs’ resistance.

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“…Exon 19 deletion, and exon 21 L858R point mutation are the most common EGFR mutations corresponding to 85–90% of cases; they usually confer sensitivity to EGFR-TKIs treatment. The remaining mutations are called uncommon and include rare EGFR mutations and complex EGFR mutations, accounting for 10–15%; they have variable predictive values ( 6 ). In addition, it is not rare to find a combination of EGFR mutations ( 1 ).…”

mentioning

confidence: 99%

What the future holds: BBT-176, beyond third-generation EGFR tyrosine kinase inhibitors

Laface,

Fedele

2024

Transl Lung Cancer Res

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Uncommon EGFR Mutations in Non-Small Cell Lung Cancer and Their Impact on the Treatment

Cited by 5 publications

References 62 publications

Advancement of regulating cellular signaling pathways in NSCLC target therapy via nanodrug

Advancement of regulating cellular signaling pathways in NSCLC target therapy via nanodrug

The Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: From Molecular Mechanisms to Clinical Application of New Therapeutic Strategies

What the future holds: BBT-176, beyond third-generation EGFR tyrosine kinase inhibitors

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