Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epidermal growth factor receptor and notch signaling in non-small-cell lung cancer.

ABSTRACT: Lung cancer is the most common reason of cancer deaths and about 85% of these are non-small-cell lung cancer. Currently, lung cancer therapy is mainly based on the tumor node metastasis (TNM) disease staging and tumor histological classification. Despite therapeutic innovations, the prognosis for lung cancer patients has not significantly changed in the last years. Therefore, a proper understanding of cell signaling pathways involved in cancer pathogenesis seems to be essential for improvement in cancer therapy field. The knowledge of crosstalk between epidermal growth factor receptor (EGFR) and Notch pathway can lead to enhanced screening for the expression of these genes allowing patients to optimize treatment options and predict potential treatment resistance. This review focuses on recent advances related to the mechanisms of EGFR and Notch signaling in non-small-cell lung cancer and the effectiveness of current Notch- and EGFR-targeted therapies.

SUBMITTER: Pancewicz-Wojtkiewicz J

PROVIDER: S-EPMC5224843 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Epidermal growth factor receptor and notch signaling in non-small-cell lung cancer.

Pancewicz-Wojtkiewicz Joanna J

Cancer medicine 20161021 12

Lung cancer is the most common reason of cancer deaths and about 85% of these are non-small-cell lung cancer. Currently, lung cancer therapy is mainly based on the tumor node metastasis (TNM) disease staging and tumor histological classification. Despite therapeutic innovations, the prognosis for lung cancer patients has not significantly changed in the last years. Therefore, a proper understanding of cell signaling pathways involved in cancer pathogenesis seems to be essential for improvement i ...[more]

PMID: 27770511

Similar Datasets

[Immunotherapy in Epidermal Growth Factor Receptor-mutant ?Non-small Cell Lung Cancer].

Project description:Targeted therapy and immunotherapy are important treatments for non-small cell lung cancer (NSCLC). At present, the clinical and basic research of epidermal growth factor receptor (EGFR) mutation NSCLC is still in the exploratory stage, needing to optimize the efficacy, combination, sequence and dosage of immunotherapy and other treatments, to clarify the relationship between EGFR mutation, immune microenvironment and the efficacy of immunotherapy. In this review, we summarized the newly updated data about immunotherapy in EGFR mutant NSCLC in term of pre-clinical study, programmed cell death protein ligand 1 (PD-L1) expression, tumor mutation burden and treatment.?.

| S-EPMC6717865 | biostudies-literature

Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer.

Project description:Epidermal growth factor receptor (EGFR) mutations are the second most common oncogenic driver event in non-small cell lung cancer (NSCLC). Classical activating mutations (exon 19 deletions and the L858R point mutation) comprise the vast majority of EGFR mutations and are well defined as strong predictors for good clinical response to EGFR tyrosine kinase inhibitors (EGFRi). However, low frequency mutations including point mutations, deletions, insertions and duplications occur within exons 18-25 of the EGFR gene in NSCLC and are associated with poorer responses to EGFRi. Despite an increased uptake of more sensitive detection methods to identify rare EGFR mutations in patients, our understanding of the biology of these rare EGFR mutations is poor compared to classical mutations. In particular, clinical data focused on these mutations is lacking due to their rarity and challenges in trial recruitment, resulting in an absence of effective treatment strategies for many low frequency EGFR mutations. In this review, we describe the structural and mechanistic features of rare EGFR mutations in NSCLC and discuss the preclinical and clinical evidence for EGFRi response for individual rare EGFR mutations. We also discuss EGFRi sensitivity for complex EGFR mutations, and conclude by offering a perspective on the outstanding questions and future steps required to make advances in the treatment of NSCLC patients that harbour rare EGFR mutations.

| S-EPMC7083237 | biostudies-literature

Tumor evolution in epidermal growth factor receptor mutated non-small cell lung cancer.

Project description:As the incidence of cancer increases worldwide there is an unmet need to understand cancer evolution to improve patient outcomes. Our growing knowledge of cancer cells' clonal expansion, heterogeneity, adaptation, and relationships within the tumor immune compartment and with the tumor microenvironment has made clear that cancer is a disease that benefits from heterogeneity and evolution. This review outlines recent knowledge of non-small cell lung cancer (NSCLC) pathogenesis and tumor progression from an evolutionary standpoint, focused on the role of oncogenic driver mutations as epidermal growth factor receptor (EGFR). Understanding lung cancer evolution during tumor development, growth, and under treatment pressures is crucial to improve therapeutic interventions and patient outcomes.

| S-EPMC7330358 | biostudies-literature

Epidermal growth factor receptor tyrosine kinase inhibitors for non-small cell lung cancer.

Project description:First-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib and erlotinib, have proven to be highly effective agents for advanced non-small cell lung cancer (NSCLC) in patients harboring an activating EGFR mutation such as the exon 19 deletion mutation and L858R. Although those reversible small molecular targeted agents provide a significant response and survival benefit, all responders eventually acquire resistance. Second-generation EGFR-targeting agents, such as irreversible EGFR/HER2 tyrosine kinase inhibitors and pan-HER TKIs, may improve survival further and be useful for patients who acquired resistance to ﬁrst-generation EGFR-TKIs. This review discusses novel therapeutic strategies for EGFR-mutated advanced NSCLC using first- and second-generation EGFR-TKIs.

| S-EPMC4129529 | biostudies-literature

Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer.

Project description:Frequent overexpression of epidermal growth factor receptor (EGFR) in non-small-cell lung cancer (NSCLC) makes EGFR a new therapeutic target. Two specific EGFR tyrosine kinase inhibitors, gefitinib (ZD1839, Iressa) and erlotinib (OSI-774, Tarceva), have been developed and approved by the US Food and Drug Administration for second-line and third-line treatment of advanced NSCLC. Clinical trials have shown considerable variability in the response rate between different patients with NSCLC, which led to the discovery of somatic EGFR-activating mutations. This brief review summarises the discovery and functional consequences of the mutations, their clinicopathological features and significant implications in the treatment and prognosis of NSCLC.

| S-EPMC2598028 | biostudies-literature

Parthenolide inhibits the growth of non-small cell lung cancer by targeting epidermal growth factor receptor.

Project description:Background: EGFR tyrosine kinase inhibitors (TKIs) have been developed for the treatment of EGFR mutated NSCLC. Parthenolide, a natural product of parthenolide, which belongs to the sesquiterpene lactone family and has a variety of biological and therapeutic activities, including anti-cancer effects. However, its effect on non-small cell lung cancer is little known.Methods: The CCK8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell apoptosis. In silico molecular docking was used to evaluate the binding of parthenolide to EGFR. Network pharmacology analysis was was used to evaluate the key gene of parthenolide target NSCLC. Western blotting was used to evaluate the key proteins involved apoptosis and EGFR signalling. The effect of parthenolide treatment in vivo was determined by using a xenograft mouse model.Results: In this study, parthenolide could induce apoptosis and growth inhibition in the EGFR mutated lung cancer cells. Parthenolide also reduces the phosphorylation of EGFR as well as its downstream signaling pathways MAPK/ERK and PI3K/Akt. Molecular docking analysis of EGFR binding site with parthenolide show that the anti-cancer effect of parthenolide against NSCLC is mediated by a strong binding to EGFR. Network pharmacology analysis show parthenolide suppresses NSCLC via inhibition of EGFR expression. In addition, parthenolide inhibits the growth of H1975 xenografts in nude mice, which is associated with the inhibition of the EGFR signaling pathway.Conclusions: Taken together, these results demonstrate effective inhibition of parthenolide in NSCLC cell growth by targeting EGFR through downregulation of ERK and AKT expression, which could be promisingly used for patients carrying the EGFR mutation.

| S-EPMC7686780 | biostudies-literature

miR-134 inhibits non-small cell lung cancer growth by targeting the epidermal growth factor receptor.

Project description:The epidermal growth factor receptor (EGFR) is frequently activated in a wide range of solid tumours and represents an important therapeutic target. MicroRNAs (miRNAs) have recently been recognized as a rational and potential modality for anti-EGFR therapies. However, more EGFR-targeting miRNAs need to be explored. In this study, we identified a novel EGFR-targeting miRNA, miRNA-134 (miR-134), in non-small-cell lung cancer (NSCLC) cell lines. Luciferase assays confirmed that EGFR is a direct target of miR-134. In addition, the overexpression of miR-134 inhibited EGFR-related signaling and suppressed NSCLC cells proliferation by inducing cell cycle arrest and/or apoptosis, suggesting that miR-134 functions as a tumour suppressor in NSCLC. Further mechanistic investigation including RNAi and rescue experiments suggested that the down-regulation of EGFR by miR-134 partially contributes to the antiproliferative role of miR-134. Last, in vivo experiments demonstrated that miR-134 suppressed tumour growth of A549 xenograft in nude mice. Taken together, our findings suggest that miR-134 inhibits non-small cell lung cancer growth by targeting the EGFR.

| S-EPMC4891324 | biostudies-literature

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway.

Project description:Most advanced non-small-cell lung cancers (NSCLCs) with activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions or L858R) initially respond to the EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. However, over time (median of 6-12 months), most tumors develop acquired resistance to EGFR TKIs. Intense research in these NSCLCs has identified two major mechanisms of resistance to gefitinib/erlotinib: secondary resistance mutations and "oncogene kinase switch" systems. The secondary T790M mutation occurs in 50% of EGFR-mutated patients with TKI resistance, and in vitro, this mutation negates the hypersensitivity of activating EGFR mutations. Sensitive detection methods have identified a proportion of TKI-naive tumors that carry T790M, and these resistant clones may be selected after exposure to gefitinib or erlotinib. Other secondary resistance mutations (D761Y, L747S, T854A) seem to be rare. The amplification of the MET oncogene is present in 20% of TKI-resistant tumors; however, in half of the cases with this "oncogene kinase switch" mechanism the T790M is coexistent. It is possible that other kinases (such as insulin-like growth factor-1 receptor [IGF-1R]) might also be selected to bypass EGFR pathways in resistant tumors. The growing preclinical data in EGFR-mutated NSCLCs with acquired resistance to gefitinib or erlotinib has spawned the initiation or conception of clinical trials testing novel EGFR inhibitors that in vitro inhibit T790M (neratinib, XL647, BIBW 2992, and PF-00299804), MET, or IGF-1R inhibitors in combination with EGFR TKIs, and heat shock protein 90 inhibitors. Ongoing preclinical and clinical research in EGFR-mutated NSCLC has the potential to significantly improve the outcomes of patients with these somatic mutations.

| S-EPMC2758558 | biostudies-literature

Combining chemotherapy with epidermal growth factor receptor inhibition in advanced non-small cell lung cancer.

Project description:Treatment of advanced stage lung cancer is changing rapidly. With the new found knowledge on molecular targets such as the epidermal growth factor receptor (EGFR), effective therapy is now available in a selected population with the target mutation. Single-agent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a standard first-line therapy for patients with activating-EGFR mutation such as base-pair deletion in exon 19 or point mutation at exon 21. At the same time, this class of drugs may be combined with chemotherapy. Studies on the concurrent combination of chemotherapy and EGFR-TKI confirmed a lack of efficacy. A phase II study on sequential intercalated combination has demonstrated an improvement in progression-free survival (PFS), but this needs to be validated by the ongoing phase III study. The third approach is to combine EGFR-TKI as maintenance therapy after tumour response or stable disease to cytotoxic chemotherapy. Two phase III studies have shown improvement in PFS, but the use of biomarkers for the selection of maintenance therapy remains debatable. Cetuximab is a monoclonal antibody against EGFR and its combination with chemotherapy was shown to improve overall survival in an unselected population. A new biomarker using the H-score will help to select patients for this combination.

| S-EPMC3384091 | biostudies-literature

Quantitative Biomarkers for Prediction of Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Cancer.

Project description:ObjectivesTo predict epidermal growth factor receptor (EGFR) mutation status using quantitative radiomic biomarkers and representative clinical variables.MethodsThe study included 180 patients diagnosed as of non-small cell lung cancer (NSCLC) with their pre-therapy computed tomography (CT) scans. Using a radiomic method, 485 features that reflect the heterogeneity and phenotype of tumors were extracted. Afterwards, these radiomic features were used for predicting epidermal growth factor receptor (EGFR) mutation status by a least absolute shrinkage and selection operator (LASSO) based on multivariable logistic regression. As a result, we found that radiomic features have prognostic ability in EGFR mutation status prediction. In addition, we used radiomic nomogram and calibration curve to test the performance of the model.ResultsMultivariate analysis revealed that the radiomic features had the potential to build a prediction model for EGFR mutation. The area under the receiver operating characteristic curve (AUC) for the training cohort was 0.8618, and the AUC for the validation cohort was 0.8725, which were superior to prediction model that used clinical variables alone.ConclusionRadiomic features are better predictors of EGFR mutation status than conventional semantic CT image features or clinical variables to help doctors to decide who need EGFR tyrosine kinase inhibitor (TKI) treatment.

| S-EPMC6002350 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data