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https://www.readbyqxmd.com/read/29342193/analysis-of-copy-number-loss-of-the-erbb4-receptor-tyrosine-kinase-in-glioblastoma
#1
DeAnalisa C Jones, Adriana Scanteianu, Matthew DiStefano, Mehdi Bouhaddou, Marc R Birtwistle
Current treatments for glioblastoma multiforme (GBM)-an aggressive form of brain cancer-are minimally effective and yield a median survival of 14.6 months and a two-year survival rate of 30%. Given the severity of GBM and the limitations of its treatment, there is a need for the discovery of novel drug targets for GBM and more personalized treatment approaches based on the characteristics of an individual's tumor. Most receptor tyrosine kinases-such as EGFR-act as oncogenes, but publicly available data from the Cancer Cell Line Encyclopedia (CCLE) indicates copy number loss in the ERBB4 RTK gene across dozens of GBM cell lines, suggesting a potential tumor suppressor role...
2018: PloS One
https://www.readbyqxmd.com/read/29341459/multicenter-study-of-diagnostic-procedures-genetic-aberration-analysis-and-first-line-treatment-of-lung-cancer-in-jiangsu-province-china
#2
YangBo Hu, Huan Hu, LiYun Miao, Xin Zhao, Wei Gu, Wei Heng, ZiLi Meng, Jian Feng, Yi You, XingXiang Xu, Rong Hu, HaiQuan Li, Jie Zhao, XiaoLi Zhu, MeiQi Shi, Li Shen, XiuWei Zhang, XiaoWei Yin, Hang Ma, MinHua Shi, Yong Yu, Hong Lv, LiMing Cai, GaoHua Feng, YeQing Zhang, Feng Wu, TangFeng Lv, Yong Song
BACKGROUND: Jiangsu Province, China, is highly developed economically and culturally, and has a high prevalence of lung cancer. We aimed to evaluate the diagnostic procedures, genetic aberration analysis status, and first-line treatment models of lung cancer in Jiangsu Province. METHODS: Lung cancer patients diagnosed in 2016 at 22 tertiary care hospitals were evaluated. Demographic characteristics, tumor histology, staging, family history of lung cancer, auxiliary examinations, genetic testing, and first-line treatment were collected on discharge...
January 17, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29341374/validation-of-the-digital-pcr-system-in-tyrosine-kinase-inhibitor-resistant-egfr-mutant-non-small-cell-lung-cancer
#3
Katsuhiro Masago, Shiro Fujita, Akito Hata, Chiyuki Okuda, Yuko Yoshizumi, Reiko Kaji, Nobuyuki Katakami, Yukio Hirata, Yasushi Yatabe
The aim of this study was to compare the accuracy of the QuantStudio 3D Digital polymerase chain reaction (dPCR) system and a PCR-based next generation sequencing (NGS) system for detecting a secondary mutation in the epidermal growth factor receptor (EGFR) gene T790M in non-small cell lung cancer (NSCLC) patients previously diagnosed with EGFR-activating mutations. Twenty-five patients with NSCLC previously treated with EGFR-TKIs were examined. The patients were treated daily with either erlotinib or gefitinib...
January 17, 2018: Pathology International
https://www.readbyqxmd.com/read/29340107/a-comparison-of-arms-plus-and-droplet-digital-pcr-for-detecting-egfr-activating-mutations-in-plasma
#4
Xinxin Zhang, Ning Chang, Guohua Yang, Yong Zhang, Mingxiang Ye, Jing Cao, Jie Xiong, Zhiping Han, Shuo Wu, Lei Shang, Jian Zhang
In this study, we introduce a novel amplification refractory mutation system (ARMS)-based assay, namely ARMS-Plus, for the detection of epidermal growth factor receptor (EGFR) mutations in plasma samples. We evaluated the performance of ARMS-Plus in comparison with droplet digital PCR (ddPCR) and assessed the significance of plasma EGFR mutations in predicting efficacy of EGFR-tyrosine kinase inhibitor (TKI) regimen. A total of 122 advanced non-small cell lung cancer (NSCLC) patients were enrolled in this study...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340050/molecular-characteristics-and-clinical-outcomes-of-egfr-exon-19-indel-subtypes-to-egfr-tkis-in-nsclc-patients
#5
Jian Su, Wenzhao Zhong, Xuchao Zhang, Ying Huang, Honghong Yan, Jinji Yang, Zhongyi Dong, Zhi Xie, Qing Zhou, Xiaosui Huang, Danxia Lu, Wenqing Yan, Yi-Long Wu
Patients with non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions and L858R) benefit from EGFR tyrosine kinase inhibitors (TKIs). However, some researchers have reported that responses to TKIs differ by subtypes of EGFR exon 19 mutations. We retrospectively analyzed EGFR exon 19 deletion subtypes and their correlation with clinical outcomes of treatment with TKIs. A cohort of 2664 consecutive patients with NSCLC was enrolled. A total of 440 EGFR exon 19 deletions were defined as 39 subtypes...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340043/clinical-significance-of-yap1-activation-in-head-and-neck-squamous-cell-carcinoma
#6
Young-Gyu Eun, Dongjin Lee, Young Chan Lee, Bo Hwa Sohn, Eui Hyun Kim, Sun Young Yim, Kee Hwan Kwon, Ju-Seog Lee
By analyzing the genomic data of head and neck squamous cell cancer (HNSCC), we investigated clinical significance of YAP1 activation. Copy number and mRNA expression of YAP1 were analyzed together to assess clinical relevance of YAP1 activation in HNSCC. The clinical significance of YAP1 activation was further validated in four independent test cohorts. We also assessed the correlation of YAP1 activation with genomic alterations such as copy number alteration, somatic mutation, and miRNA expression. The YAP1-activated (YA) subgroup showed worse prognosis for HNSCC as tested and validated in five cohorts...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340039/integrative-molecular-network-analysis-identifies-emergent-enzalutamide-resistance-mechanisms-in-prostate-cancer
#7
Carly J King, Josha Woodward, Jacob Schwartzman, Daniel J Coleman, Robert Lisac, Nicholas J Wang, Kathryn Van Hook, Lina Gao, Joshua Urrutia, Mark A Dane, Laura M Heiser, Joshi J Alumkal
Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors harbor countless genomic aberrations that control many hallmarks of cancer. While some specific mutations in CRPC may be actionable, many others are not. We hypothesized that genomic aberrations in cancer may operate in concert to promote drug resistance and tumor progression, and that organization of these genomic aberrations into therapeutically targetable pathways may improve our ability to treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant CRPC, we performed transcriptional and copy number profiling studies using paired enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29337640/molecular-determinants-of-response-to-anti-programmed-cell-death-pd-1-and-anti-programmed-death-ligand-pd-l-ligand-1-blockade-in-patients-with-non-small-cell-lung-cancer-profiled-with-targeted-next-generation-sequencing
#8
Hira Rizvi, Francisco Sanchez-Vega, Konnor La, Walid Chatila, Philip Jonsson, Darragh Halpenny, Andrew Plodkowski, Niamh Long, Jennifer L Sauter, Natasha Rekhtman, Travis Hollmann, Kurt A Schalper, Justin F Gainor, Ronglai Shen, Ai Ni, Kathryn C Arbour, Taha Merghoub, Jedd Wolchok, Alexandra Snyder, Jamie E Chaft, Mark G Kris, Charles M Rudin, Nicholas D Socci, Michael F Berger, Barry S Taylor, Ahmet Zehir, David B Solit, Maria E Arcila, Marc Ladanyi, Gregory J Riely, Nikolaus Schultz, Matthew D Hellmann
Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known. Methods Detailed clinical annotation and response data were collected for patients with advanced non-small-cell lung cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240)...
January 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29337243/intratumoral-morphological-heterogeneity-can-be-an-indicator-of-genetic-heterogeneity-in-colorectal-cancer
#9
Juliane Büttner, Korinna Jöhrens, Frederick Klauschen, Michael Hummel, Dido Lenze, Wolfgang Saeger, Annika Lehmann
Anti-EGFR-targeted therapy is used to treat metastatic colorectal cancers with RAS wild-type. However, resistance to targeted therapy is often observed and can be primary or acquired. One reason for primary resistance is the presence of mutations that are undetected due to genetic heterogeneity, which can be expressed by differences present in primary tumor and distant metastasis or recurrence or by an intratumoral heterogeneity (presence of different subclones in the investigated tumor sample). The aim of our study was to investigate if morphological heterogeneity can be an indicator of intratumoral heterogeneity...
January 11, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29337056/comparison-of-epithelial-mesenchymal-transition-mediated-tyrosine-kinase-inhibitor-resistance-in-non-small-cell-lung-cancer-cell-lines-with-wild-type-egfr-and-mutant-type-egfr
#10
Tsatsral Iderzorig, Joseph Kellen, Chike Osude, Sanjana Singh, James A Woodman, Christian Garcia, Neelu Puri
In the United States, lung cancer is the second most common cancer in men and women. In 2017, 222,500 new cases and 155,870 deaths from lung cancer are estimated to have occurred. A tyrosine kinase receptor, epidermal growth factor receptor (EGFR) is over expressed or mutated in non-small cell lung cancer (NSCLC) resulting in increased cell proliferation and survival. Tyrosine kinase inhibitors (TKIs) are currently being used as therapy for NSCLC patients, however, they have limited efficacy in NSCLC patients due to acquisition of resistance...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29336166/optimizing-outcomes-in-egfr-mutation-positive-nsclc-which-tyrosine-kinase-inhibitor-and-when
#11
Nicolas Girard
Despite the efficacy of standard-of-care EGFR tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib and afatinib, in EGFR mutation-positive non-small-cell lung cancer, resistance develops, most commonly due to the T790M mutation. Osimertinib showed clinical activity in the treatment of T790M-positive disease following progression on a first-line TKI, and is approved in this setting. Recently, osimertinib improved efficacy versus first-generation TKIs (erlotinib and gefitinib) in the first-line setting. Multiple factors can influence first-line treatment decisions, including subsequent therapy options, presence of brain metastases and tolerability, all of which should be considered in the long-term treatment plan...
January 16, 2018: Future Oncology
https://www.readbyqxmd.com/read/29336009/gefitinib-for-advanced-non-small-cell-lung-cancer
#12
REVIEW
Esther Ha Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
BACKGROUND: The role of gefitinib for the treatment of advanced non-small cell lung cancer (NSCLC) is evolving. We undertook a systematic review to evaluate the available evidence from all randomised trials. OBJECTIVES: To determine the effectiveness and safety of gefitinib as first-line, second-line or maintenance treatment for advanced NSCLC. SEARCH METHODS: We performed searches in CENTRAL, MEDLINE and Embase from inception to 17 February 2017...
January 16, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29335443/elucidating-the-genomic-architecture-of-asian-egfr-mutant-lung-adenocarcinoma-through-multi-region-exome-sequencing
#13
Rahul Nahar, Weiwei Zhai, Tong Zhang, Angela Takano, Alexis J Khng, Yin Yeng Lee, Xingliang Liu, Chong Hee Lim, Tina P T Koh, Zaw Win Aung, Tony Kiat Hon Lim, Lavanya Veeravalli, Ju Yuan, Audrey S M Teo, Cheryl X Chan, Huay Mei Poh, Ivan M L Chua, Audrey Ann Liew, Dawn Ping Xi Lau, Xue Lin Kwang, Chee Keong Toh, Wan-Teck Lim, Bing Lim, Wai Leong Tam, Eng-Huat Tan, Axel M Hillmer, Daniel S W Tan
EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to EGFR tyrosine kinase inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent and early whole-genome doubling, aneuploidy, and high clonal diversity. Multiple truncal alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on cell cycle dysregulation, with late sector-specific high-amplitude amplifications and deletions that potentially beget drug resistant clones...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29334606/the-association-of-acquired-t790m-mutation-with-clinical-characteristics-after-resistance-to-first-line-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-in-lung-adenocarcinoma
#14
Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Kun-Chieh Chen, Chia-Hung Hsu, Kang-Yi Su, Jeremy J W Chen, Huei-Wen Chen, Sung-Liang Yu, Tsung-Ying Yang, Gee-Chen Chang
Purpose: The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients with acquired resistance after first-line EGFR‒tyrosine kinase inhibitor (TKI) treatment. Materials and Methods: We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status...
January 4, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29332537/azd9291-increases-sensitivity-to-radiation-in-pc-9-ir-cells-by-delaying-dna-damage-repair-after-irradiation-and-inducing-apoptosis
#15
Shenghai Wu, Lucheng Zhu, Linglan Tu, Sumei Chen, Haixiu Huang, Jingjing Zhang, Shenglin Ma, Shirong Zhang
AZD9291 is a novel, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which is administered orally. It has been proven effective in non-small cell lung cancer (NSCLC) patients, with both EGFR-sensitizing and EGFR T790M mutations in preclinical models. However, the potential therapeutic effects of AZD9291 combined with other modalities, including ionizing radiation, are not well understood. The presence of AZD9291 significantly increases the cell-killing effects of radiation in PC-9-IR cells with a secondary EGFR mutation (T790M), which was developed from NSCLC PC-9 cells (human lung adenocarcinoma cell with EGFR 19 exon 15 bp deletion) after chronic exposure to increasing doses of gefitinib, and in H1975 cells (human lung adenocarcinoma cell with EGFR exon 20 T790M mutation de novo), but not in PC-9 cells or in H460 cells (human lung adenocarcinoma cell with wild-type EGFR)...
January 13, 2018: Radiation Research
https://www.readbyqxmd.com/read/29332331/egfr-mutations-and-tumor-metastases-in-patients-with-nonsmall-cell-lung-cancer-in-the-south-of-russia
#16
Oleg I Kit, Dmitry I Vodolazhsky, Natalia N Timoshkina, Lubov' Yu Vladimirova, Igor N Turkin, Ksenia A Kutsyn, Yaroslav S Enin, Svetlana B Panina, Vladimir Jurisic
PURPOSE: To assess the frequencies of somatic EGFR mutations in the tumor tissues of patients with non-small cell lung cancer (NSCLC) residing in the South of Russia (SR), and to define the relationship between genetic subtypes of NSCLC and the emergence of different types of metastases. METHODS: DNA was extracted from formalin-fixed parrafin embedded (FFPE) samples of 721 patients. A total of 29 somatic EGFR mutations were detected using commercial Therascreen EGFR RGQ PCR Kit...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331751/comprehensive-genomic-profiling-of-head-and-neck-squamous-cell-carcinoma-reveals-fgfr1-amplifications-and-tumour-genomic-alterations-burden-as-prognostic-biomarkers-of-survival
#17
C Dubot, V Bernard, M P Sablin, S Vacher, W Chemlali, A Schnitzler, G Pierron, K Ait Rais, N Bessoltane, E Jeannot, J Klijanienko, O Mariani, T Jouffroy, V Calugaru, C Hoffmann, M Lesnik, N Badois, F Berger, C Le Tourneau, M Kamal, I Bieche
BACKGROUND: We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value. PATIENTS AND METHODS: We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis...
January 10, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#18
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29330617/characterizing-genomic-differences-of-human-cancer-stratified-by-the-tp53-mutation-status
#19
Mengyao Wang, Chao Yang, Xiuqing Zhang, Xiangchun Li
The key roles of the TP53 mutation in cancer have been well established. TP53 is the most frequently mutated gene, and its inactivation is widespread among human cancer types. However, the landscape of genomic alterations in human cancers stratified by the TP53 mutation has not yet been described. We obtained somatic mutation and copy number change data of 6551 regular-mutated samples from the Cancer Genome Atlas (TCGA) and compared significantly mutated genes (SMGs), copy number alterations, mutational signatures and mutational strand asymmetries between cancer samples with and without the TP53 mutation...
January 12, 2018: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/29329944/use-of-superarms-egfr-mutation-detection-kit-to-detect-egfr-in-plasma-cell-free-dna-of-patients-with-lung-adenocarcinoma
#20
Shaohua Cui, Lin Ye, Huimin Wang, Tianqing Chu, Yizhuo Zhao, Aiqin Gu, Liwen Xiong, Chunlei Shi, Liyan Jiang
BACKGROUND: The SuperARMS EGFR Mutation Detection Kit (SuperARMS) is highly selective and sensitive and able to detect 41 of the most common somatic mutations in exons 18 to 21 of the epidermal growth factor receptor gene (EGFR). It allows for the detection of 0.2% to 0.8% mutant DNA in a background of 99.8% to 99.2% normal DNA. The present study assessed the performance of SuperARMS in detecting EGFR mutations in cell-free DNA (cfDNA) samples derived from plasma in patients with advanced lung adenocarcinoma...
December 21, 2017: Clinical Lung Cancer
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