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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of the epidermal growth factor receptor (EGFR) has been observed in human breast tumors and is associated with poor prognosis in breast cancer patients. This would suggest that blocking the activity of the EGFR is a logical approach in the treatment of breast cancer. Three 20-mer phosphorothioate oligodeoxynucleotides were designed to target different regions of the human epidermal growth factor receptor (EGFR) mRNA. Several analogs of these oligodeoxynucleotides (the 2'-fluoro analog, the 2'-propoxy analog, and/or the 5-methyl cytosine analog) were also evaluated. We added these compounds to a human ovarian carcinoma cell line (SKOV3) and a human lung carcinoma line (A549), both of which overexpress the EGFR. All of these antisense oligonucleotides inhibited expression of the 10 kb EGFR mRNA (range: 22-97% inhibition) compared to a scrambled control oligonucleotide or an untreated control. Expression of the less prominent 5.6 kb EGFR mRNA band was also inhibited by all but two of the parent oligonucleotides. No inhibition of this 5.6 kb band was found with the control oligonucleotide. The reduction in the expression of EGFR mRNA by the three most potent antisense compounds was accompanied by a significant reduction of EGFR protein (90-98%) and in vitro growth inhibition of SKOV3 cells as compared to the control oligonucleotide.
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PMID:Antisense oligonucleotides to the epidermal growth factor receptor. 1020 71

The ErbB family of receptor tyrosine kinases, of which the epidermal growth factor receptor (EGFR) is the prototype, is associated with the formation and malignant progression of most of the common solid tumors. These molecules play a key role in a complex network of signal transduction pathways that function in normal development as well as in neoplastic transformation. The EGFR and other family members are therefore promising targets for new anticancer therapies. In normal tissues, EGFR-tyrosine kinase (TK) activity is strictly controlled. However, in tumor cells, there are multiple mechanisms that can lead to increased or inappropriate EGFR-TK activity, including altered expression of EGFR, its ligand, or interacting molecules; decreased deactivation through phosphatases or downregulation; or mutation of the EGFR protein. Novel therapeutic approaches aimed at inhibiting increased EGFR-TK activity include antibodies that block the extracellular ligand-binding site, antibody or ligand fusion proteins that specifically target toxins to the tumor cells, or small-molecule TK inhibitors (TKIs) that act intracellularly to block downstream signal transduction from EGFR. Studies have shown that such blockade can lead to reduced cellular proliferation, inhibition of survival signals, and inhibition of tumor metastasis and angiogenesis. Additionally, some agents, including EGFR antibodies and TKIs such as gefitinib have been demonstrated to be effective against various human solid tumors in preclinical models and have shown activity in advanced non-small-cell lung cancer and other solid tumors.
Clin Lung Cancer 2003 Sep
PMID:The impact of gefitinib on epidermal growth factor receptor signaling pathways in cancer. 1464 88

Treatment of second- and third-line patients with non-small-cell lung carcinoma (NSCLC) with the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib significantly increased survival relative to placebo. Whereas patient tumors with EGFR mutations have shown responses to EGFR inhibitors, an exclusive role for mutations in patient survival benefit from EGFR inhibition is unclear. Here we show that wild-type EGFR-containing human NSCLC lines grown both in culture and as xenografts show a range of sensitivities to EGFR inhibition dependent on the degree to which they have undergone an epithelial to mesenchymal transition (EMT). NSCLC lines which express the epithelial cell junction protein E-cadherin showed greater sensitivity to EGFR inhibition in vitro and in xenografts. In contrast, NSCLC lines having undergone EMT, expressing vimentin and/or fibronectin, were insensitive to the growth inhibitory effects of EGFR kinase inhibition in vitro and in xenografts. The differential sensitivity of NSCLC cells with epithelial or mesenchymal phenotypes to EGFR inhibition did not correlate with cell cycle status in vitro or with xenograft growth rates in vivo, or with total EGFR protein levels. Cells sensitive to EGFR inhibition, with an epithelial cell phenotype, did exhibit increased phosphorylation of EGFR and ErbB3 and a marked increase in total ErbB3. The loss of E-cadherin and deregulation of beta-catenin associated with EMT have been shown to correlate with poor prognosis in multiple solid tumor types. These data suggest that EMT may be a general biological switch rendering non-small cell lung tumors sensitive or insensitive to EGFR inhibition.
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PMID:Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. 1623 Apr 9

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity to tyrosine kinase inhibitors (TKIs) and are present in 10-30% of non-small cell lung carcinoma depending on ethnic origin. EGFR protein is also overexpressed in about 90% of squamous cell carcinoma of head and neck (HNSCC), and treatment with TKIs has shown clinical benefit in a subgroup of these patients. Recently, EGFR mutations were described in three Asian patients with larynx cancer. We screened for EGFR tyrosine kinase mutations in tumour DNA of 100 patients of Caucasian origin with HNSCC by direct sequencing of the hotspot regions. Only one patient with larynx cancer displayed a novel, somatic EGFR missense mutation, K745R, affecting a highly conserved residue within the ATP cleft. Similar to reports in lung cancer, EGFR kinase domain mutations in HNSCC patients seem to show a lower incidence in patients of Caucasian origin.
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PMID:Low incidence of mutations in EGFR kinase domain in Caucasian patients with head and neck squamous cell carcinoma. 1632 36

The epidermal growth factor receptor (EGFR) is overexpressed in many epithelial malignancies, against which some antitumoral drugs have been developed. There is a lack of information as to EGFR expression in malignant pleural mesothelioma (MPM), an aggressive and fatal cancer poorly responsive to current oncological treatments. Our aim was to: (a) compare EGFR immunohistochemical expression with mRNA levels measured by real time PCR; (b) assess the relationships between EGFR expression and clinico-pathological data including survival; (c) analyze the EGFR mutations. We developed an immunohistochemical method of EGFR evaluation based on the number of immunoreactive cells and staining intensity in 61 MPMs. EGFR immunoreactivity was documented in 34/61 (55.7%) cases. A significant correlation between EGFR protein and mRNA levels (p = 0.0077) was found, demonstrating the reliability of our quantification method of EGFR membrane expression. Radically resected patients (p = 0.005) and those with epithelial histotype (p = 0.048) showed an increased survival. No statistical correlation between EGFR immunoreactivity and patients survival was observed. No EGFR mutation was documented. This study documents EGFR overexpression in MPM at the protein and the transcriptional levels; it proposes a reliable method for EGFR expression evaluation in MPM. EGFR levels are not associated with clinico-pathological features of patients, including survival.
Lung Cancer 2006 Feb
PMID:EGFR overexpression in malignant pleural mesothelioma. An immunohistochemical and molecular study with clinico-pathological correlations. 1638 23

We evaluated epidermal growth factor receptor (EGFR) protein expression by immunohistochemical analysis and EGFR gene amplification by fluorescence in situ hybridization in 199 consecutive newly diagnosed and surgically treated patients with primary non-small cell lung carcinoma (NSCLC) and correlated results with clinicopathologic findings. EGFR protein expression was more common in squamous cell carcinoma (SCC; 17 [26.2%]) than in adenocarcinoma (14 [11.1%]; (P = .0076) and more frequently associated with EGFR amplification (8 [14.5%] vs 4 [3.6%] cases; P = .0208). Poor differentiation was associated with a higher average number of EGFR gene copies per cell (mean, 4.18; P = .0322) and a higher EGFR/chromosome 7 ratio (mean, 1.84; P = .0324). N0 disease showed a higher number of EGFR gene copies (mean, 4.196; P = .0163). SCCs demonstrated a higher EGFR/chromosome 7 ratio than adenocarcinomas (mean, 1.95 vs 1.47; P = .0324), particularly T1 tumors (mean, 1.79; P = .0243). Statistical analysis failed to show correlation between outcome and EGFR protein expression and gene amplification in early NSCLC. EGFR protein expression was uncoupled from gene amplification in most cases, although good correlation occurred in a subset of SCCs.
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PMID:Significance of EGFR protein expression and gene amplification in non-small cell lung carcinoma. 1669 Apr 85

In response to the paper by Popat et al. "Recurrent responses to non-small-cell lung cancer brain metastases with erlotinib", we wish to report a similar case and to provide comments. A 32-year-old Chinese never-smoker female presented a primary lung adenocarcinoma with brain metastasis and three subsequent responses to EGFR tyrosine kinase inhibitors (gefitinib and erlotinib). Direct sequencing of epidermal growth factor receptor (EGFR) gene exons 18 to 21 and K-ras gene was performed on tissue obtained from initial biopsies and post-chemotherapy surgical specimens. An EGFR exon 21 L858R point mutation was identified on pre- and post-chemotherapy samples. K-ras mutations and EGFR exon 20 T790M point mutations were not detected. Moreover, EGFR protein overexpression was observed by immunohistochemistry as well as EGFR gene high polysomy by fluorescent in situ hybridization. These case suggest that re-challenging patients with NSCLC several times with EGFR-TKI should be considered when progressive disease is observed under chemotherapy. However, we do not yet know whether this option should be considered in light of tumor molecular evaluation, or whether it should be proposed to patients who experienced a clinical response after a first administration.
Lung Cancer 2007 Dec
PMID:Subsequent brain metastasis responses to epidermal growth factor receptor tyrosine kinase inhibitors in a patient with non-small-cell lung cancer. 1715 52

This study was conducted to evaluate the prevalence of EGFR and KIT mutations in thymomas and thymic carcinomas as a means of exploring the potential for molecularly targeted therapy with tyrosine kinase inhibitors. Genomic DNA was isolated from 41 paraffin-embedded tumor samples obtained from 24 thymomas and 17 thymic carcinomas. EGFR exons 18, 19, and 21, and KIT exons 9, 11, 13, and 17, were analyzed for mutations by PCR and direct sequencing. Protein expression of EGFR and KIT was evaluated immunohistochemically. EGFR mutations were detected in 2 of 20 thymomas, but not in any of the thymic carcinomas. All of the EGFR mutations detected were missense mutations (L858R and G863D) in exon 21. EGFR protein was expressed in 71% of the thymomas and 53% of the thymic carcinomas. The mutational analysis of KIT revealed only a missense mutation (L576P) in exon 11 of one thymic carcinoma. KIT protein was expressed in 88% of the thymic carcinomas and 0% of the thymomas. The results of this study indicate that EGFR and KIT mutations in thymomas and thymic carcinomas are rare, but that many of the tumors express EGFR or KIT protein.
Lung Cancer 2008 Dec
PMID:Mutational status of EGFR and KIT in thymoma and thymic carcinoma. 1844 88

Recent years have brought tremendous progress in the development of genomic and proteomic platforms to study cancer biology. Tests based on these platforms are helpful in early diagnosis, prognosis, and prediction of treatment benefit. Molecular studies performed on minimally invasive material (plasma, sputum) from individuals participating in longitudinal or case-control studies have approximately 70%-90% sensitivity and specificity to detect lung cancer. In operable non-small-cell lung cancer, genomic and proteomic studies yield better prognostic information than pathologic staging. There are several examples of successful identification of predictive assays for benefit from chemotherapy (ERCC1, RRM1, p27Kip1, and p53 expression) or targeted therapies (epidermal growth factor receptor [EGFR] gene copy number, EGFR activating mutations, EGFR protein expression, serum proteomic profile). These markers should be prospectively tested in clinical studies before they can be routinely used in the clinic.
Clin Lung Cancer 2008 Mar
PMID:Advances in genomic and proteomic studies of non-small-cell lung cancer: clinical and translational research perspective. 1850 Oct 93

To evaluate the epidermal growth factor receptor (EGFR) protein expression and increased copy number as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC), we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR increased copy number and EGFR protein expression statuses in 109 surgically treated NSCLC cases. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR increased copy number was defined as Cappuzzo et al. criteria. FISH positive was found from 36/109 (33.0%) lung cancer patients, including 30 high polysomy cases and 6 gene amplification cases. FISH-positive cases were significantly correlated with worse prognosis (log-rank test p=0.0097). Within EGFR-mutant patients (n=55), FISH-positive cases were also correlated with poor prognosis (p=0.0255). FISH-negative tumors were found to be more frequently well-differentiated histology. Smoking status (never smoker vs. smoker, p=0.1510), and gender (p=0.5248) did not correlated with FISH positive. EGFR IHC results were correlated with FISH results (p=0.004), but not correlated with prognosis (p=0.2815). Although EGFR FISH-positive rate did not correlated with EGFR mutation (p=0.1973), EGFR polysomy or amplification cases were correlated with EGFR mutations (p=0.0023). In conclusion, the EGFR FISH-positive rate in Japanese patients with NSCLC was similar to rates in Western populations, unlike the higher frequencies of EGFR mutation in East Asians. A high EGFR gene copy number might have shorter survival in NSCLC.
Lung Cancer 2009 Jun
PMID:Epidermal growth factor receptor gene amplification in surgical resected Japanese lung cancer. 1905 70


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