Abstract. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686) and hold promise to further boost the median survival of patients with EGFR mutated NSCLC. Nature. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. 2020 Dec 17. doi: 10.1038/s41388-020-01597-1. Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors. PURPOSE: The vast majority of epidermal growth factor receptor (EGFR) mutations occur in lung adenocarcinoma, and even rare cases of other subtypes with this mutation, such as adenosquamous cell carcinoma, are associated with adenocarcinoma histology. 2014;106: doi: 10.1093/jnci/djt361. Correlate the presence of EGFR mutation in blood with EGFR mutation in primary or metastatic NSCLC tumor block. doi: 10.1097/MD.0000000000023503. 2008 Jun;60 Suppl 2:S10-8. Epidermal growth factor receptor mutation; gefitinib; molecular targeted therapy; non–small cell lung cancer; SMAP; Non–small cell lung cancer (NSCLC) is the most common cause of death by cancer worldwide ().As the global burden of NSCLC continues to increase, new agents are being developed for more effective treatment within a wide range of modalities, including surgery, … Epidermal growth factor receptor (EGFR) mutations are the second most common oncogenic driver event in non-small cell lung cancer (NSCLC). Mendelsohn J. Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data S.E.D.C. In response to exposure to tobacco smoke, this epithelium becomes initially hyperplastic, then metaplastic, and then frankly dysplastic. Medicine (Baltimore). Mutations in the epidermal growth factor receptor (EGFR) are drivers of a subset of lung cancers. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. Non-small-cell lung cancer (NSCLC), the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review. -, Thorgeirsson TE, Geller F, Sulem P, Rafnar T, Wiste A, Magnusson KP, et al. Secondary EGFR mutations such as EGFR T790M commonly lead to resistance to these agents, limiting their long-term efficacy. The epidermal growth factor receptor (EGFR) has emerged as an attractive therapeutic target for patients with non–small-cell lung cancer (NSCLC). Effectiveness of Tyrosine Kinase Inhibitors in Japanese Patients with Non-small Cell Lung Cancer Harboring Minor Epidermal Growth Factor Receptor Mutations: Results from a Multicenter Retrospective Study (HANSHIN Oncology Group 0212). Amivantamab (JNJ-61186372) is a low fucose, fully human immunoglobulin G1 (IgG1)-based bispecific antibody directed against epidermal growth factor receptor (EGFR) and (A) Results from patients harboring the EGFR resistance mutation T790M (9 patients) are shown. Purpose: In this phase I study (BLOOM), osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was evaluated in patients with leptomeningeal metastases (LMs) from EGFR-mutated (EGFRm) advanced non-small-cell lung cancer (NSCLC) whose disease had progressed on previous EGFR-TKI therapy.  |   |  Epidermal growth factor receptor mutations were more prevalent in adenocarcinomas than in non-adenocarcinoma histological types. There was a higher prevalence of KRAS mutations in the non-Asian patients. NIH National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. 2020 Oct;12(10):5505-5516. doi: 10.21037/jtd-19-3570. Epidermal growth factor receptor (…, Figure 2.  |  Background. Establishment of multiplex allele-specific blocker PCR for enrichment and detection of 4 common. Searching for a magic bullet in NSCLC: the role of epidermal growth factor receptor mutations and tyrosine kinase inhibitors. Determine if epidermal growth factor receptor (EGFR) mutation exists in the peripheral blood of patients with advanced non-small cell lung cancer (NSCLC). N Engl J Med. Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers have generated enormous interest, because they predict for … 2020 Nov;8(22):1509. doi: 10.21037/atm-20-6754. Online ahead of print. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs). Oncogene. We review the results of genetic, biochemical and clinical studies focused on somatic mutations of EGFR that are associated with the phenomenon of oncogene addiction, describing 'oncogenic shock' as a mechanistic explanation for the apoptosis that follows the acute treatment of susceptible cells with kinase inhibitors. Jorge, S.S. Kobayashi and D.B. Differentiating synchronous double primary lung adenocarcinomas from intrapulmonary metastasis by CT features, EGFR mutations and ALK rearrangement status. cancers. USA.gov. doi: 10.1016/S0169-5002(08)70100-4. Bell DW, Gore I, Okimoto RA, Godin-Heymann N, Sordella R, Mulloy R, Sharma SV, Brannigan BW, Mohapatra G, Settleman J, Haber DA. Activating mutations in the epidermal growth factor receptor (EGFR) gene occur in 10–20% of Caucasian and at least 50% of Asian non-small cell lung cancer (NSCLC) patients [,,, ]. Codons in exon 18, 19, 20, and 21 are shown in blue, yellow, red, and green, respectively. Rational Computational Design of Fourth-Generation EGFR Inhibitors to Combat Drug-Resistant Non-Small Cell Lung Cancer. Please enable it to take advantage of the complete set of features! J Cancer Res Clin Oncol. Conformational Insight on WT- and Mutated-EGFR Receptor Activation and Inhibition by Epigallocatechin-3-Gallate: Over a Rational Basis for the Design of Selective Non-Small-Cell Lung Anticancer Agents. However, despite its almost universal presence in NSCLC tumors, therapeutic inhibition of EGFR has resulted in significant tumor regressions in only 10% to 20% of patients. Germline mutations in driver oncogenes and inherited lung cancer risk independent of smoking history. Patients with epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer derive significant clinical benefit from treatment with the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR) gene mutations. The epidermal growth factor receptor (EGFR) is a validated therapeutic target in non-small cell lung cancer (NSCLC). Background Most patients with non–small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). So far these mutations have been extensively characterized in established cell lines. CA Cancer J Clin. The discovery that sensitizing epidermal growth factor receptor (EGFR) mutations are predictive for therapeutic benefit from EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib marked the beginning of a new era in lung cancer therapeutics. Lung Cancer. Mutation in epidermal growth factor receptor (EGFR) gene is one of the principal mechanisms leading to tumorigenesis of non‐small‐cell lung cancer (NSCLC), and was found in up to 50% of Asian, female patients who never smoked. -, Brennan P, Hainaut P, Boffetta P. Genetics of lung-cancer susceptibility. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Background: Many patients with non–small-cell lung cancer (NSCLC) who achieve radiographic responses to treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib have somatic mutations in the EGFR tyrosine kinase domain. Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond. Epidermal growth factor receptor (EGFR) gene mutations are important for the pathogenesis of lung adenocarcinoma, and the tyrosine kinase function of EGFR is a promising target for the treatment of non-small cell lung cancer.In patients with advanced lung adenocarcinoma, those harboring EGFR mutations have longer survival than those without EGFR mutations, mainly due to the … The discovery that somatic mutations in the epidermal growth factor receptor (EGFR) gene are found in a subset of lung adenocarcinomas and are associated with sensitivity to the EGFR tyrosine kinase inhibitors (TKI) gefitinib (1, 2) and erlotinib (3) has generated excitement among clinicians and researchers studying non–small cell lung cancer (NSCLC). Clinical impact of switching to a second EGFR-TKI after a severe AE related to a first EGFR-TKI in EGFR-mutated NSCLC. Cheng FJ, Chen CH, Tsai WC, Wang BW, Yu MC, Hsia TC, Wei YL, Hsiao YC, Hu DW, Ho CY, Li TS, Wu CY, Chou WY, Yu YL, Tang CH, Chen CY, Chen CM, Hsu JL, Chen HF, Chen Y, Tu CY, Hung MC, Huang WC. 2008 May;21 Suppl 2:S16-22. 2020 Mar 3;21(5):1721. doi: 10.3390/ijms21051721. Abstract. This site needs JavaScript to work properly. The amount of EGFR … Understanding the genetic heterogeneity of epithelial tumours and devising strategies to circumvent their rapid acquisition of resistance to targeted kinase inhibitors are essential to the successful use of targeted therapies in common epithelial cancers. Balak MN, Gong Y, Riely GJ, et al. Introduction In patients with non-small cell lung cancer (NSCLC), the predictive value of rare epidermal growth factor receptor (EGFR) exon 20 mutations in determining a patient’s response to EGFR tyrosine kinase inhibitor (TKI) treatment is unclear. Clipboard, Search History, and several other advanced features are temporarily unavailable. Responses were most pronounced in female non‐smokers with adenocarcinoma histology.  |  Targeted therapy for these lung cancers has been established based on evidence regarding mainly common mutations; that is, exon 19 deletions (Del19) and L858R. Minnelli C, Laudadio E, Mobbili G, Galeazzi R. Int J Mol Sci. The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) has been linked to activating mutations in the EGFR gene. In lung cancer, the molecules gefitinib and erlotinib which target the intracellular kinase domain of the epidermal growth factor receptor (EGFR), cause significant tumour responses and, in the case of erlotinib, a survival benefit in patients with previously treated cancers. 2011;61:69–90. The KRASoncogene also plays an important role in the development of lung cancer. In 2004, several investigators reported that somatic mutations in the epidermal growth factor receptor gene were associated with clinical responses to erlotinib and gefitinib in patients with non–small cell lung cancer. Yu Z, Boggon TJ, Kobayashi S, Jin C, Ma PC, Dowlati A, Kern JA, Tenen DG, Halmos B. 2020 Nov 15;17(4):842-863. doi: 10.20892/j.issn.2095-3941.2020.0005. Clipboard, Search History, and several other advanced features are temporarily unavailable. In recent years, the treatment of non‐small cell lung cancer (NSCLC), especially with EGFR inhibitors, has made rapid progress, and the median progression‐free survival (PFS) of patients with EGFR gene‐sensitive mutations has been significantly prolonged. Patients and Methods We reviewed data for NSCLC patients harboring EGFR exon 20 mutations from two hospitals in Korea. 2011 Nov;13(11):812-8. doi: 10.1007/s12094-011-0739-1. Lynch TJ, Bell DW, Sordella R, et al. Costa. doi: 10.1038/nature06846. Epub 2012 Mar 28. Somatic mutations in the epidermal growth factor receptor (EGFR) gene are present in approximately 20% (in Caucasians) to 40% (in East Asians) of adenocarcinomas of the lung. Lung adenocarcinomas with mutated epidermal growth factor receptor have significant responses to tyrosine kinase inhibitors, although for unselected patients it does not appear to have a survival benefit. Lung cancers with EGFR gene mutations tend to respond to treatments that specifically target the overactive epidermal growth factor receptor protein that allows cancer cells to constantly grow and divide. Your story matters Citation Jorge, S.E.D.C., S.S. Kobayashi, and D.B. Method: The related database was systematically searched with keywords until … doi: 10.1038/modpathol.3801018. Lung adenocarcinomas with mutated epidermal growth factor receptor have significant responses to tyrosine kinase inhibitors, although for unselected patients it … This study assesses different technologies for detecting epidermal growth factor receptor (EGFR) mutations from circulating tumor DNA in patients with EGFR T790M‐positive advanced non–small cell lung cancer (NSCLC) from the AURA3 study (NCT02151981), and it evaluates clinical responses to osimertinib and platinum‐pemetrexed according to the plasma T790M status. Cancer Res. This study was prospectively designed to evaluate a phase II study of gefitinib for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations… Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions) make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. Lancet Oncol. Epidermal growth factor receptor ( EGFR ) mutations in non-small-cell lung cancer (NSCLC). Ann Transl Med. Background: Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity. 2020 Mar;146(3):767-775. doi: 10.1007/s00432-019-03103-x. The epidermal growth factor receptor (EGFR) is a validated therapeutic target in non-small cell lung cancer (NSCLC). Lung cancer; Mutations; Epidermal growth factor receptor (EGFR), a transmembrane glycoprotein, is related to the proliferation and resistance to apoptosis of cells. Targeted therapy for these lung cancers has been established based on evidence regarding mainly common mutations; that is, exon 19 deletions (Del19) and L858R. 2012 Jun;42(6):528-33. doi: 10.1093/jjco/hys042. doi: 10.3322/caac.20107. -, Siegel R, Ma J, Zou Z, Jemal A. 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