Epidermal growth factor receptor (EGFR): A rising star in the era of precision medicine of lung cancer

Liu, Xiaomin; Wang, Ping; Zhang, Caiyan; Ma, Zhongliang

doi:10.18632/oncotarget.16854

Cited by 163 publications

(139 citation statements)

References 98 publications

(65 reference statements)

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“…Functional experiments demonstrated that miR-539 exhibited as an oncogene in epithelial ovarian cancer [16] while as a tumour suppressor in other three types of cancers [17][18][19]. Besides that, EGFR, an oncogenic driver of lung cancer [20], was found as a target gene of miR-539 [21]. Based on these reason, we focused on investigating whether lidocaine functions to lung cancer cells through regulating miR-539.…”

Section: Introductionmentioning

confidence: 99%

Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis

Sun

2019

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Despite the medical uses of lidocaine has been well-characterized, the study of lidocaine's pharmacological function other the anaesthetic effect was never stopped. This study designed to reveal the effect of lidocaine on the growth and metastasis of lung cancer in vitro. Methods: A549 and NCI-H1299 cells were treated by lidocaine for 24 h. miR-539 expression in cell was silenced by transfection with the specific inhibitor. The changes in cell growth and metastasis were determined using CCK-8 assay and western blot. Luciferase activity assay was performed to assay if EGFR was a target of miR-539. Western blot was used to test the activation of EGFR downstream signalling. Results: Lidocaine suppressed the viability, migration, and invasion of A549 and NCI-H1299 cells while induced apoptotic death. Lidocaine elevated the expression of miR-539. The anti-tumour properties of lidocaine towards A549 and NCI-H1299 cells were partially attenuated when miR-539 was silenced. EGFR was a target of miR-539. Lidocaine repressed the activation of ERK and PI3K/AKT pathways also via regulating miR-539. Conclusion: The anti-growth and anti-metastatic effects of lidocaine towards lung cancer cells. The anti-tumour properties of lidocaine may be partial via up-regulation of miR-539, which blocked EGFR signalling by directly binding with EGFR.

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Section: Introductionmentioning

confidence: 99%

Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis

Sun

2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…In terms of entropy, SLC5A2 is involved in only two processes at L1, consolidating into a single aggregate at L886. A distinctly different behavior is identified for the epithelial growth factor receptor (EGFR) also being included in the multi-analyte panel tested in oncology indications [23,24]. EGFR as target, with major drugs including Cetuximab and Erlotinib, is embedded in 147 processes at L1, and shows one of the highest entropy courses of the given biomarker set.…”

Section: Information Content Of Biomarkersmentioning

confidence: 99%

Biomarkers for capturing disease pathology as molecular process hyperstructure

Lukas

Heinzel

Mayer

2019

Preprint

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Background: Precision of drugs in clinical development but also of approved treatment sees limits, documented as attrition in clinical stage drug testing and suboptimal number needed to treat in clinical practice. Precision medicine aims at approaching a causal relation of disease pathology, treatment mechanism of action and clinical outcome. The instance linking pathology, clinical phenotype and drug response is disease characteristics amenable for quantitation, including established clinical phenotyping parameters and upcoming molecular profiling and biomarkers. Molecular biomarkers situated at the interface of pathology-specific molecular process architecture and drug mechanism of action promise capturing aspects allowing assessment of treatment response. Results: Approximating a set of 1,008 disease terms as pathology molecular networks provides 3,860 molecular processes involving 4,602 protein coding genes. Assembling this process set in a hierarchical cluster using mean shortest paths among processes as distance measure allows representation of molecular processes in cumulative aggregation. This procedure transforms human disease pathology into a static instance of a molecular process hyperstructure involving 1,340 aggregate levels in a molecular architecture. The hyperstructure allows evaluating molecular biomarker candidates at different levels of molecular process aggregation in terms of biomarker-specific entropies. Interpretation as information content reflects the capacity of a biomarker for sensing molecular process configuration. Deriving entropies across aggregation levels for a reference set of 1,502 biomarker candidates identifies significant spread in information content of individual biomarkers. Exemplified on biomarker panels holding evidence for prognostic capacity and factors serving as drug targets from selected chronic diseases, biomarker entropies allow interpretation in terms of sensitivity for capturing process context and specificity for informing on the status of individual processes afflicted with a given pathology. Conclusions: High entropy biomarkers provide candidate molecular proxies for clinical phenotyping parameters, and low entropy biomarkers add information on specifics of disease pathology. Combining high and low entropy biomarkers in panels may offer relevant resolution of molecular process configurations for improving patient stratification with respect to minimizing variance in drug response.

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“…Gefitinib and erlotinib were the first two reversible inhibitors of EGFR, followed by the second generation of inhibitors (afatinib, dacomitinib, neratinib and canertinib) designed to overcome clinical resistance [16]. The third generation of EGFR inhibitors (osimertinib) was developed to target the resistance produced by the T790M mutation [17], where the aberrant change of the normal threonine with a methionine as the gatekeeper residue increases the affinity for ATP [18]. Close to 60% of patients with melanoma harbor various mutations of B-RAF that cause activation of the MAPK pathway.…”

Section: Introductionmentioning

confidence: 99%

In Search of Outliers. Mining for Protein Kinase Inhibitors Based on Their Anti-Proliferative NCI-60 Cell Lines Profile

Ion

Nițulescu

2020

Molecules

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Protein kinases play a pivotal role in signal transduction, protein synthesis, cell growth and proliferation. Their deregulation represents the basis of pathogenesis for numerous diseases such as cancer and pathologies with cardiovascular, nervous and inflammatory components. Protein kinases are an important target in the pharmaceutical industry, with 48 protein kinase inhibitors (PKI) already approved on the market as treatments for different afflictions including several types of cancer. The present work focuses on facilitating the identification of new PKIs with antitumoral potential through the use of data-mining and basic statistics. The National Cancer Institute (NCI) granted access to the results of numerous previously tested compounds on 60 tumoral cell lines (NCI-60 panel). Our approach involved analyzing the NCI database to identify compounds that presented similar growth inhibition (GI) profiles to that of existing PKIs, but different from approved oncologic drugs with other mechanisms of action, using descriptive statistics and statistical outliers. Starting from 34,000 compounds present in the database, we filtered 400 which displayed selective inhibition on certain cancer cell lines similar to that of several already-approved PKIs.

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Epidermal growth factor receptor (EGFR): A rising star in the era of precision medicine of lung cancer

Cited by 163 publications

References 98 publications

Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis

Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis

Biomarkers for capturing disease pathology as molecular process hyperstructure

In Search of Outliers. Mining for Protein Kinase Inhibitors Based on Their Anti-Proliferative NCI-60 Cell Lines Profile

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