egfr mutation wiki
20 十二月 2020

Vanaf stadium 3 moet nierfalen behandeld worden. 2017 Apr;13(4):2425-2431. doi: 10.3892/ol.2017.5740. Dieser genetische Defekt tritt mit einer Häufigkeit von ca. EGFR: EGF-Rezeptor (Epidermal Growth Factor Receptor) eGFR: Geschätzte glomeruläre Filtrationsrate (estimated glomerular filtration rate) Tags: Abkürzung. Die EGFR-T790M-Mutation des epidermalen Wachstumsfaktor-Rezeptors ( englisch Epidermal Growth Factor Receptor) wurde als Ursache einer erworbenen Resistenz von Lungenadenokarzinomen gegen Gefitinib oder Erlotinib entdeckt. targeted therapy) sind unter anderem Gefitinib (Iressa), Erlotinib (Tarceva) und Afatinib (Giotrif) oder die monoklonalen Antikörper Cetuximab (Erbitux) und Panitumumab (Vectibix). Estimated glomerular filtration rate (eGFR), a measure of renal function. These mutations are displayed at the amino acid level across the full length of the gene by default. Interruption of EGFR signalling, either by blocking EGFR binding sites on the extracellular domain of the receptor or by inhibiting intracellular tyrosine kinase activity, can prevent the growth of EGFR-expressing tumours and improve the patient's condition. Vorhandene Strukturdaten: Ektodomäne: 1IVO, 1MOX, 1NQL, 1YY9, 3B2U, 3B2V, 3C09; Juxtamembran-Domäne: 1Z9I (NMR); Tyrosinkinase: 1M14, 1M17, 1XKK, 2EB2, 2EB3, 2GS2, 2GS6, 2GS7, 2ITN, 2ITO, 2ITP, 2ITQ, 2ITT, 2ITU, 2ITV, 2ITW, 2ITX, 2ITY, 2ITZ, 2J5E, 2J5F, 2J6M, 2JIT, 2JIU, 2JIV, 2RF9, 2RFD, 2RFE, 2RGP, 3BEL, 3BUO, 3GOP, 3GT8. The pathogenicity of the EGFR mutation was supported by in vitro experiments and functional analysis of a skin biopsy. The overall EGFR mutation frequency was 16.6%, and the highest mutation frequencies were observed in exon 19 (6.4%) and exon 21 (7.3%). Top Disease Cases with EGFR Mutation Around 90% of these mutations are due to exon 19 deletion or exon 21 L858R point mutation. Die Mutation des EGFR ersetzt ein Threonin (T) durch ein Methionin (M) an Position 790 von Exon 20.[2]. • They attack the EGFR mutation in your cancer cells • They usually don’t harm healthy cells, which means that side effects could be mild • Standard treatment is 1 pill a day, so the treatment won't keep you from going about your usual activities. The most common adverse effect of EGFR inhibitors, found in more than 90% of patients, is a papulopustular rash that spreads across the face and torso; the rash's presence is correlated with the drug's antitumor effect. Cetuximab and panitumumab are examples of monoclonal antibody inhibitors. Der EGF-Rezeptor (Abkürzung für englisch Epidermal Growth Factor Receptor, EGFR) ist ein Protein in Zellmembranen von Wirbeltieren; es ist der Rezeptor für den Epidermal-Growth-Factor (EGF) und ist ein Mitglied der ErbB-Familie, eine Unterfamilie von vier eng verwandten Rezeptor-Tyrosinkinasen: EGFR1/HER1 (ErbB-1), HER2/c-neu (ErbB-2), HER3 (ErbB-3) und HER4 (ErbB-4). Er dient, Somatic Mutations in Epidermal Growth Factor Receptor DataBase, https://de.wikipedia.org/w/index.php?title=EGF-Rezeptor&oldid=193908729, „Creative Commons Attribution/Share Alike“. eGFR steht für: estimated GFR, die geschätzte glomeruläre Filtrationsrate, ein Maß für die Nierenfunktion. In the case of EGFR-positive non small cell lung cancer (NSCLC), a mutation, or damage, in a gene causes the EGFR to … The cobas ® EGFR Mutation Test v2 is a real-time PCR test that identifies 42 mutations in exons 18, 19, 20 and 21 of the epidermal growth factor receptor (EGFR) gene, including the T790M resistant mutation.. Mutations in EGFR can occur at different locations on exon 18 to 21. Es sind zahlreiche weitere Mutationen bekannt, von denen man weiß, dass sie an der Entstehung von Lungenkrebs beteiligt sind. Die Struktur des EGFR-Monomers besteht aus: der Ektodomäne (extrazelluläre Domäne) mit zwei homologen Domänen I (L1) und III (L2) und den cysteinreichen Domänen II (CR1 bzw. Clear results. [23][24] Aberrant persistence of myofibroblasts within tissues can lead to progressive tissue fibrosis, impairing tissue or organ function (e.g. Gallant JN et al. De eGFR is minder dan 15 milliliter per minuut. Weil es sich bei Patienten mit del19- oder Leu858Arg-Mutation offensichtlich um unterschiedliche Populationen handelte, sollten sie in … EGFR is found at abnormally high levels in cancer cells, and EGFR activation appears to be important in tumor growth and progression. 40 Prozent ist es mutiert. 170 liter per dag. gillian.ellison@astrazeneca.com Wichtiger Hinweis zu diesem Artikel Diese Seite wurde zuletzt am 20. November 2019 um 22:50 Uhr bearbeitet. [18] In glioblastoma a specific mutation of EGFR, called EGFRvIII, is often observed. Eine Hemmung der EGF-Rezeptoren führt zur Verlangsamung des Tumorwachstums oder sogar zur Tumorregression. CimaVax-EGF, an active vaccine targeting EGF as the major ligand of EGF, uses a different approach, raising antibodies against EGF itself, thereby denying EGFR-dependent cancers of a proliferative stimulus;[29] it is in use as a cancer therapy against non-small-cell lung carcinoma (the most common form of lung cancer) in Cuba, and is undergoing further trials for possible licensing in Japan, Europe, and the United States. Defined EGFR mutations are detected using DNA isolated from formalin-fixed paraffin-embedded tumor tissue (FFPET) or circulating-free tumor DNA (cfDNA) from plasma derived from … The EGFR gene provides instructions for making a receptor protein called the epidermal growth factor receptor, which spans the cell membrane so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. These downstream signaling proteins initiate several signal transduction cascades, principally the MAPK, Akt and JNK pathways, leading to DNA synthesis and cell proliferation. It has been reported that mutations in exon 19 were the most common of all EGFR mutations. Two primary sources of resistance are the T790M Mutation and MET oncogene. EGFR has been shown to play a critical role in TGF-beta1 dependent fibroblast to myofibroblast differentiation. [32] However, as of 2010 there was no consensus of an accepted approach to combat resistance nor FDA approval of a specific combination. De eGFR CKD-EPI van 45 tot 60 ml/min is beter dan de eGFR MDRD. Der EGF-Rezeptor wird in verschiedenen Tumorarten hochreguliert und/oder in mutierter Form vorgefunden, was dazu führt, dass die Tumorzellen unkontrolliert wachsen und sich vermehren. EGFR may refer to: Epidermal growth factor receptor (EGFR), a transmembrane receptor protein in humans. Tumors with EGFR gene amplification frequently contain EGFR gene rearrangements, with the most common extracellular domain mutation being EGFRvIII. In contrast, no relationship was noted between KRAS mutation status and SUVmax. More recently AstraZeneca has developed Osimertinib, a third generation tyrosine kinase inhibitor.[27]. Die Mutation des EGFR ersetzt ein Threonin (T) durch ein Methionin (M) an Position 790 von Exon 20. Confident decisions. [36], Laboratory research using genetically engineered stem cells to target EGFR in mice was reported in 2014 to show promise. EGFR mutations can be detected in tumour tissue, cytology specimens and blood from lung cancer patients. The epidermal growth factor receptor (EGFR) is overexpressed in a variety of human epithelial tumors, often as a consequence of gene amplification. EGFR mutations were generally assumed to give rise to spontaneous kinase activation, eliminating the dependence of the cancer mutants on dimerisation for activation. EGFR - Explore an overview of EGFR, with a histogram displaying coding mutations, full tabulated details of all associated variants, tissue distribution and any drug resistance data. In other words, there are many ways in which EGFR can be changed genetically. Epidermal growth factor receptor has been shown to interact with: In fruitflies, the epidermal growth factor receptor interacts with Spitz.[99]. [33] In 10% to 15% of patients the effects can be serious and require treatment. Europe: EntroGen’s EGFR Mutation Analysis Kit is available for research (RUO) and diagnostic (CE-IVD) purposes. The cobas ® EGFR Mutation Test v2 is a real-time PCR test for the qualitative detection of defined mutations of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) patients. Yang schlussfolgert aus diesen Ergebnissen, dass die Erstlinienbehandlung mit Afatinib Standard bei Patienten mit Del19-Mutation sein sollte. The monoclonal antibodies block the extracellular ligand binding domain. Die häufigsten EGFR-Varianten sind Deletionen in Exon 19 (Del19) und die Exon 21 Leu858Arg-Variante (85-90%). Jump to navigation Jump to search. 2 Department of Surgical Oncology, Tata Memorial … In einigen Tumoren sind EGF-Rezeptoren überexprimiert. The identification of EGFR as an oncogene has led to the development of anticancer therapeutics directed against EGFR (called "EGFR inhibitors"), including gefitinib,[25] erlotinib, afatinib, brigatinib and icotinib[26] for lung cancer, and cetuximab for colon cancer. EGFR mutations were more frequent in tumors with lower SUVmax. [39] The feasibility of in vivo imaging of EGFR expression has been demonstrated in several studies.[40][41]. Patients who harbor an EGFR mutation have a 60% response rate to erlotinib. His clinical features included a papulopustular rash, dry skin, chronic diarrhoea, abnormalities of hair growth, breathing difficulties and electrolyte imbalances.[22]. mit aktivierenden EGFR-Mutationen und unverändertem Krankheitszustand nach First-Line-Therapie Zweitlinie: bei NSCLC mit oder ohne EGFR-Mutation Metastasiertes Pankreaskarzinom: Erstlinie: in Kombination mit Gemcitabin: Zum Einsatz von Erlotinib als Erstmedikation und in der Kombinationstherapie bei Lungenkrebs werden zurzeit Studien durchgeführt. In Folge kann es zu einer verstärkten Metastasenbildung kommen. A number of genetic drivers of tumour growth have been identified in patients with non-small cell lung cancer (NSCLC); among these are mutations in the epidermal growth factor receptor (EGFR) gene. Ferner gibt es auch geringere Sensitivität gegenüber Chemo- und Radiotherapie. 1xkk: EGFR kinase domain complexed with a quinazoline inhibitor- GW572016, 1yy9: Structure of the extracellular domain of the epidermal growth factor receptor in complex with the Fab fragment of cetuximab/Erbitux/IMC-C225, 1z9i: A Structural Model for the Membrane-Bound Form of the Juxtamembrane Domain of the Epidermal Growth Factor Receptor, 2gs2: Crystal Structure of the active EGFR kinase domain, 2gs6: Crystal Structure of the active EGFR kinase domain in complex with an ATP analog-peptide conjugate, 2gs7: Crystal Structure of the inactive EGFR kinase domain in complex with AMP-PNP, 2itn: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AMP-PNP, 2ito: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH IRESSA, 2itp: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AEE788, 2itq: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AFN941, 2itt: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN L858R MUTATION IN COMPLEX WITH AEE788, 2itu: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN L858R MUTATION IN COMPLEX WITH AFN941, 2itv: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN L858R MUTATION IN COMPLEX WITH AMP-PNP, 2itw: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AFN941, 2itx: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AMP-PNP, 2ity: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH IRESSA, 2itz: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN L858R MUTATION IN COMPLEX WITH IRESSA, 2j5e: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 13-JAB, 2j5f: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 34-JAB, 2j6m: CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AEE788, note, a full list of the ligands able to activate EGFR and other members of the ErbB family is given in the, transmembrane receptor protein tyrosine kinase activity, transmembrane signaling receptor activity, phosphatidylinositol-4,5-bisphosphate 3-kinase activity, Ras guanyl-nucleotide exchange factor activity, epidermal growth factor-activated receptor activity, multivesicular body, internal vesicle lumen, positive regulation of protein phosphorylation, negative regulation of epidermal growth factor receptor signaling pathway, positive regulation of MAP kinase activity, negative regulation of protein catabolic process, transmembrane receptor protein tyrosine kinase signaling pathway, positive regulation of fibroblast proliferation, positive regulation of epithelial cell proliferation, activation of phospholipase A2 activity by calcium-mediated signaling, regulation of peptidyl-tyrosine phosphorylation, positive regulation of nitric oxide biosynthetic process, regulation of nitric-oxide synthase activity, cellular response to epidermal growth factor stimulus, positive regulation of transcription from RNA polymerase II promoter, positive regulation of synaptic transmission, glutamatergic, positive regulation of ERK1 and ERK2 cascade, positive regulation of superoxide anion generation, positive regulation of cell proliferation, cellular response to dexamethasone stimulus, negative regulation of mitotic cell cycle, cellular response to growth factor stimulus, GO:0007243 intracellular signal transduction, positive regulation of production of miRNAs involved in gene silencing by miRNA, positive regulation of smooth muscle cell proliferation, positive regulation of inflammatory response, positive regulation of prolactin secretion, regulation of transcription from RNA polymerase II promoter, positive regulation of protein kinase C activity, negative regulation of ERBB signaling pathway, positive regulation of protein localization to plasma membrane, negative regulation of cardiocyte differentiation, cellular response to reactive oxygen species, positive regulation of transcription, DNA-templated, positive regulation of blood vessel diameter, positive regulation of NIK/NF-kappaB signaling, epidermal growth factor receptor signaling pathway, positive regulation of peptidyl-serine phosphorylation, regulation of phosphatidylinositol 3-kinase signaling, positive regulation of protein kinase B signaling, positive regulation of nitric oxide mediated signal transduction, positive regulation of cyclin-dependent protein serine/threonine kinase activity, negative regulation of Notch signaling pathway, positive regulation of canonical Wnt signaling pathway, positive regulation of G1/S transition of mitotic cell cycle, GRCh38: Ensembl release 89: ENSG00000146648, GRCm38: Ensembl release 89: ENSMUSG00000020122, "ErbB receptors: from oncogenes to targeted cancer treatment", "A comprehensive pathway map of epidermal growth factor receptor signaling", "The ADAM17-amphiregulin-EGFR axis in mammary development and cancer", "Growth factor receptor expression in anal squamous lesions: modifications associated with oncogenic human papillomavirus and human immunodeficiency virus", "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib", "Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR", "Transforming growth factor-β1 (TGF-β1)-stimulated fibroblast to myofibroblast differentiation is mediated by hyaluronan (HA)-facilitated epidermal growth factor receptor (EGFR) and CD44 co-localization in lipid rafts", "MicroRNA-7 inhibition rescues age-associated loss of epidermal growth factor receptor and hyaluronan-dependent differentiation in fibroblasts", "EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy", "Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations", "Pharmacogenetics and pharmacogenomics in oncology therapeutic antibody development", "Cuba Has a Lung Cancer Vaccine—And America Wants It", "Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials", "Skin rash could predict the response to EGFR tyrosine kinase inhibitor and the prognosis for patients with non-small cell lung cancer: a systematic review and meta-analysis", "Management of EGFR-inhibitor associated rash: a retrospective study in 49 patients", "Engineering toxin-resistant therapeutic stem cells to treat brain tumors", "Aggregation of nanoparticles in endosomes and lysosomes produces surface-enhanced Raman spectroscopy", "Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR:2377 affibody molecule labeled with 99mTc using a peptide-based cysteine-containing chelator", "ADP-ribosylation factor 4 small GTPase mediates epidermal growth factor receptor-dependent phospholipase D2 activation", "Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. There is also evidence to suggest that clusters of activated EGFRs form, although it remains unclear whether this clustering is important for activation itself or occurs subsequent to activation of individual dimers. 2018;18(1):891. doi:10.1186%2Fs12885-018-4774-y. National Cancer Institute. Users can search uncommon EGFR mutations for additional information including alternative nomenclature, exon, and mutation description Fysiologisch daalt de GFR met de leeftijd, pathologisch bij verschillende nierziektes. EGFR dimerization stimulates its intrinsic intracellular protein-tyrosine kinase activity. [37] EGFR is a well-established target for monoclonal antibodies and specific tyrosine kinase inhibitors. The other ones I won't go into as much detail. Epidermal growth factor and its receptor was discovered by Stanley Cohen of Vanderbilt University. Es handelt sich um eine einzelne Missense-Mutation, eine Punktmutation, die den Einbau einer anderen Aminosäure in ein Protein verursacht. These mutations are usually heterozygous, where the mutant allele exhibits gene amplification. Osimertinib hat eine lange Halbwertszeit von 48 Stunden. Weitere Varianten finden sich vorrangig in Exon 18 und 20. 2019 Dec;20(12):1681-1690. doi: 10.1016/S1470-2045(19)30504-2. 1–4 Diagnostic tests are available that look for the presence or absence of mutations in tumour DNA encoding the EGFR gene. Many therapeutic approaches are aimed at the EGFR. The distribution of these mutations has been found to be race-dependent, with one study estimating that 10% of Caucasians, but 50% of Asians, will be found to have such tumor markers. Epub 2019 Oct 3. [34][35], Some tests are aiming at predicting benefit from EGFR treatment, as Veristrat. Confident decisions. Hier erfolgt die Liquid Biopsy zum Nachweis einer EGFR-T790M-Mutation. Bibliography of studies using this product. J Thorac Oncol . Objectives: Epidermal growth factor receptor (EGFR) mutations have been identified in lung adenocarcinomas and are associated with high response chance to EGFR tyrosine kinase inhibitors. Die Diagnostik erfolgt symptom- und therapieorientiert, siehe Tabelle 2. The total amount of DNA in the sample is assessed by a control assay. Die Aktivierung (Dimerisierung) des EGFR erfolgt durch extrazelluläre Bindung der Liganden Epidermal Growth Factor (EGF) und Transforming Growth Factor (TGFα), dessen Signal er über Autophosphorylierung und die Rekrutierung von Signalmolekülen wie Akt/PKB, MEK oder STAT-Protein ins Zellinnere leitet (Signaltransduktion), die letztendlich das Zellwachstum stimulieren und den apoptotischen (programmierten) Zelltod verhindern. [20][21] However, its exact roles in these conditions are ill-defined. As a result, autophosphorylation of several tyrosine (Y) residues in the C-terminal domain of EGFR occurs. In stadium 2 wordt geen verder onderzoek gepland, behalve als er ook bloed en/of eiwit aanwezig is in de urine, en bij diabetespatiënten. A number of genetic drivers of tumour growth have been identified in patients with non-small cell lung cancer (NSCLC), including mutations in the epidermal growth factor receptor (EGFR) gene. Phosphatidic acid activates receptor dephosphorylation by PTP1C", "Phosphotyrosine 1173 mediates binding of the protein-tyrosine phosphatase SHP-1 to the epidermal growth factor receptor and attenuation of receptor signaling", "Transforming growth factor {beta} (TGF-{beta})-Smad target gene protein tyrosine phosphatase receptor type kappa is required for TGF-{beta} function", "NSP1 defines a novel family of adaptor proteins linking integrin and tyrosine kinase receptors to the c-Jun N-terminal kinase/stress-activated protein kinase signaling pathway", "CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases", "Shc phosphotyrosine-binding domain dominantly interacts with epidermal growth factor receptors and mediates Ras activation in intact cells", "The Sos1 and Sos2 Ras-specific exchange factors: differences in placental expression and signaling properties", "N terminus of Sos1 Ras exchange factor: critical roles for the Dbl and pleckstrin homology domains", "Carbachol-stimulated transactivation of epidermal growth factor receptor and mitogen-activated protein kinase in T(84) cells is mediated by intracellular Ca2+, PYK-2, and p60(src)", "Identification of both positive and negative domains within the epidermal growth factor receptor COOH-terminal region for signal transducer and activator of transcription (STAT) activation", "Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells", "Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis", "Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells", 10.1002/1521-1878(200008)22:8<697::AID-BIES3>3.0.CO;2-1, "Phosphorylation of calmodulin. 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