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Driver mutation lung cancer

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https://www.readbyqxmd.com/read/28438075/concomitant-presence-of-egfr-and-alk-fusion-gene-mutation-in-adenocarcinoma-of-lung-a-case-report-and-review-of-the-literature
#1
Nishitha Thumallapally, Hana Yu, Mohammad Farhan, Uroosa Ibrahim, Maricel Odiami
Empirical evidence has long suggested that oncogenic driver mutations in non-small-cell lung cancer are mutually independent. However, recent studies reported in pertinent literature reveal that concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangement can occur in a subset of patients with NSCLC. In order to shed further light on this issue, we report a case of adenocarcinoma of lung harboring both EGFR mutation in exon 21 (L861Q) and ALK rearrangement...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28435024/lkb1-deletion-in-murine-b-lymphocytes-promotes-cell-death-and-cancer
#2
George P Souroullas, Yuri Fedoriw, Louis M Staudt, Norman E Sharpless
LKB1 (aka STK11) is a potent tumor suppressor in solid tumors such as melanoma and lung adenocarcinoma, but inactivation in hematopoietic cells causes cell death, without signs of tumorigenesis. We noted somatic LKB1 deletion or mutation at low frequency in human B cell lymphoma. In order to determine if LKB1 inactivation is a passenger or driver event in lymphoid cancers, we examined the effects of conditional inactivation of Lkb1 in murine lymphocytes. Consistent with prior reports, Lkb1 deletion in either T or B cells resulted in massive, lineage-specific apoptosis...
April 20, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28433570/association-between-environmental-tobacco-smoke-exposure-and-the-occurrence-of-egfr-mutations-and-alk-rearrangements-in-never-smokers-with-non-small-cell-lung-cancer-analyses-from-a-prospective-multinational-ets-registry
#3
Ross A Soo, Akihito Kubo, Masahiko Ando, Tomoya Kawaguchi, Myung-Ju Ahn, Sai-Hong Ignatius Ou
BACKGROUND: Molecular studies have demonstrated actionable driver oncogene alterations are more frequent in never-smokers with non-small-cell lung cancer (NSCLC). The etiology of these driver oncogenes in patients with NSCLC remains unknown, and environmental tobacco smoke (ETS) is a potential cause in these cases. MATERIALS AND METHODS: We assembled clinical and genetic information for never-smoker patients with NSCLC accrued in Japan, Korea, Singapore, and the United States...
January 19, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28430586/epidermal-growth-factor-receptor-egfr-a-rising-star-in-the-era-of-precision-medicine-of-lung-cancer
#4
REVIEW
Xiaomin Liu, Ping Wang, Caiyan Zhang, Zhongliang Ma
Lung cancer is a leading cause of cancer mortality worldwide. In tumors, the important role of noncoding RNA regulatory networks has been more and more reveal. EGFR has been identified as an oncogenic driver of NSCLC, especially activating mutations EGFR and its inhibition with specific TKIs can generate dramatic tumor responses. Studies have shown that EGFR plays significant roles in the progression of NSCLC. Subset analysis of the small proportion of patients with EGFR-mutant lung cancer showed a disease-free survival benefit, but was underpowered to detect a survival advantage...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430579/antiangiogenesis-and-gene-aberration-related-therapy-may-improve-overall-survival-in-patients-with-concurrent-kras-and-tp53-hotspot-mutant-cancer
#5
Zhijie Wang, Sarina Piha-Paul, Filip Janku, Vivek Subbiah, Naiyi Shi, Jing Gong, Chetna Wathoo, Kenna Shaw, Kenneth Hess, Russell Broaddus, Aung Naing, David Hong, Apostolia M Tsimberidou, Daniel Karp, James Yao, Funda Meric-Bernstam, Siqing Fu
PURPOSE: Genetic alterations such as activating KRAS and/or inactivating TP53 are thought to be the most common drivers to tumorigenesis. Therefore, we assessed phase I cancer patients with KRAS+/TP53+ mutations. RESULTS: Approximately 8% of patients referred to phase I clinical trials harbored concurrent KRAS and TP53 mutations. Patients who received a phase I trial therapy (n = 57) had a median OS of 12 months, compared with 4.6 months in those who were not treated (n = 106; p = 0...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418914/met-exon-14-mutations-as-targets-in-routine-molecular-analysis-of-primary-sarcomatoid-carcinoma-of-the-lung
#6
Raphaël Saffroy, Vincent Fallet, Nicolas Girard, Julien Mazieres, Denis Moro Sibilot, Sylvie Lantuejoul, Isabelle Rouquette, Françoise Thivolet-Bejui, Thibaut Vieira, Martine Antoine, Jacques Cadranel, Antoinette Lemoine, Marie Wislez
MET exon 14 splicing mutations are new targetable oncogenic drivers reported in 3% of non-small cell lung cancer (NSCLC) cases and have been shown to be more common in pulmonary sarcomatoid carcinomas (PSCs). This study sought to screen mutations affecting MET exon 14 splice sites in a large SC cohort of Caucasian patients, with a large adenocarcinoma cohort as internal control.We tested 81 patients with SC and 150 with adenocarcinoma for splice site DNA mutations leading to RNA splicing-based skipping of MET exon 14...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416482/notch1-signaling-regulates-self-renewal-and-platinum-chemoresistance-of-cancer-stem-like-cells-in-human-non-small-cell-lung-cancer
#7
Yun Zhang, Wei Xu, Huiqin Guo, Yanmei Zhang, Yuexi He, Sau Har Lee, Xin Song, Xiaoyan Li, Yongqing Guo, Yunlong Zhao, Cheng Ding, Fei Ning, Yuanyuan Ma, Qun-Ying Lei, Xiaoyu Hu, Shengnan Li, Wei Guo
Cancer stem-like cells (CSC) are thought to drive tumor initiation, metastasis, relapse and therapeutic resistance, but their specific pathogenic characters in many cancers including non-small cell lung cancer (NSCLC) have yet to be well defined. Here we develop findings that the growth factor HGF promotes CSC sphere formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD-SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC). In particular, we isolated a subpopulation of CD166(+)CD49f(hi)CD104(-)Lin(-) LCSC present in all human specimens of NSCLC examined, regardless of their histological subtypes or genetic driver mutations...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28415711/mutational-analysis-of-multiple-lung-cancers-discrimination-between-primary-and-metastatic-lung-cancers-by-genomic-profile
#8
Taichiro Goto, Yosuke Hirotsu, Hitoshi Mochizuki, Takahiro Nakagomi, Daichi Shikata, Yujiro Yokoyama, Toshio Oyama, Kenji Amemiya, Kenichiro Okimoto, Masao Omata
In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature. The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399384/biomarkers-for-selection-of-therapy-for-adenocarcinoma-of-the-lung
#9
Eric H Bernicker, Ross A Miller, Phillip T Cagle
To suggest that the discovery of targetable driver mutations in many patients with advanced adenocarcinoma of the lung has completely transformed the work-up and therapeutic options for this disease would not be hyperbole. Although not curative, small-molecule tyrosine kinase inhibitors directed at oncogene-addicted tumors have led to significantly improved response rates compared with cytotoxic chemotherapy, with often manageable toxicities and better tolerance. However, the absence of reliable clinical predictors has made molecular testing essential to ensure that patients receive the proper medical management...
April 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28388009/triplet-therapy-with-afatinib-cetuximab-and-bevacizumab-induces-deep-remission-in-lung-cancer-cells-harboring-egfr-t790m-in-vivo
#10
Kenichiro Kudo, Kadoaki Ohashi, Go Makimoto, Hisao Higo, Yuka Kato, Hiroe Kayatani, Yasuko Kurata, Yoichiro Takami, Daisuke Minami, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Akiko Sato, Katsuyuki Hotta, Tadashi Yoshino, Mitsune Tanimoto, Katsuyuki Kiura
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment strategy for EGFR-mutant lung cancers; however, resistance usually occurs due to a secondary mutation, T790M, in EGFR. Combination therapy using afatinib and cetuximab has had good results in lung tumors harboring EGFR(T)(790M) mutations in clinical trials. The effect of bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, combined with EGFR-TKIs has also been investigated. We hypothesized that the dosage of afatinib and cetuximab could be reduced by combination with bevacizumab, and that the triplet therapy may result in better tumor inhibition with tolerable toxicity...
April 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28383694/genetic-variations-in-cancer-related-significantly-mutated-genes-and-lung-cancer-susceptibility
#11
Y Zhang, L Zhang, R Li, D W Chang, Y Ye, J D Minna, J A Roth, B Han, X Wu
Background: Cancer initiation and development are driven by key mutations in driver genes. Applying high-throughput sequencing technologies and bioinformatic analyses, The Cancer Genome Atlas (TCGA) project has identified panels of somatic mutations that contributed to the etiology of various cancers. However, there are few studies investigating the germline genetic variations in these significantly mutated genes (SMGs) and lung cancer susceptibility. Patients and Methods: We comprehensively evaluated 1655 tagged SNPs located in 127 SMGs identified by TCGA, and test their association with lung cancer risk in large-scale case-control study...
April 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28380484/post-progression-survival-associated-with-overall-survival-in-patients-with-advanced-non-small-cell-lung-cancer-receiving-docetaxel-monotherapy-as-second-line-chemotherapy
#12
Mie Kotake, Yosuke Miura, Hisao Imai, Keita Mori, Reiko Sakurai, Kyoichi Kaira, Yoshio Tomizawa, Koichi Minato, Ryusei Saito, Takeshi Hisada
BACKGROUND: In patients with non-small-cell lung cancer (NSCLC), the effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. Therefore, using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) and post-progression survival (PPS) with OS in patients with advanced NSCLC treated with docetaxel monotherapy as second-line chemotherapy. METHODS: Between April 2002 and December 2014, data from 86 patients with advanced NSCLC who underwent second-line docetaxel monotherapy following first-line treatment with platinum combination chemotherapy were analyzed...
April 6, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28378229/advances-in-the-development-of-molecularly-targeted-agents-in-non-small-cell-lung-cancer
#13
Saoirse O Dolly, Dearbhaile C Collins, Raghav Sundar, Sanjay Popat, Timothy A Yap
Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that involves personalized strategies based on histological and molecular subtypes. The molecular era has revolutionized the treatment of patients harboring epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 gene aberrations. In the appropriately selected population, anti-tumor agents against these molecular targets can significantly improve progression-free survival...
April 4, 2017: Drugs
https://www.readbyqxmd.com/read/28377205/molecular-testing-turnaround-time-for-non-small-cell-lung-cancer-in-routine-clinical%C3%A2-practice-confirms-feasibility-of-cap-iaslc-amp-guideline-recommendations-a-single-center-analysis
#14
Marcello DiStasio, Yigu Chen, Deepa Rangachari, Daniel B Costa, Yael K Heher, Paul A VanderLaan
INTRODUCTION: Molecular testing to identify targetable driver mutations is the standard of care for patients with advanced-stage non-small cell lung cancer. Recent guideline recommendations by the College of American Pathologists (CAP), International Association for the Study of Lung Cancer (IASLC), and Association for Molecular Pathology (AMP) established a benchmark turnaround time (TAT) target of 10 working days for results to be available to the treating oncologist and ≤ 3 days for specimens to arrive at a commercial testing laboratory if testing is not performed in-house...
March 14, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28370323/recombinant-cells-in-the-lung-increase-with-age-via-de-novo-recombination-events-and-clonal-expansion
#15
Takafumi Kimoto, Jennifer E Kay, Na Li, Bevin P Engelward
Homologous recombination (HR) is a critical DNA repair pathway, which is usually error-free, but can sometimes lead to cancer-promoting mutations. Despite the importance of HR as a driver of mutations, the spontaneous frequency of such mutations has proven difficult to study. To gain insight to location, cell type, and subsequent proliferation of mutated cells, we used the Rosa26 Direct Repeat (RaDR) mice for in situ detection and quantification of recombinant cells in the lung. We developed a method for automated enumeration of recombinant cells in lung tissue using the Metafer 4 slide-scanning platform...
April 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28359318/24h-gene-variation-effect-of-combined-bevacizumab-erlotinib-in-advanced-non-squamous-non-small-cell-lung-cancer-using-exon-array-blood-profiling
#16
Florent Baty, Markus Joerger, Martin Früh, Dirk Klingbiel, Francesco Zappa, Martin Brutsche
BACKGROUND: The SAKK 19/05 trial investigated the safety and efficacy of the combined targeted therapy bevacizumab and erlotinib (BE) in unselected patients with advanced non-squamous non-small cell lung cancer (NSCLC). Although activating EGFR mutations were the strongest predictors of the response to BE, some patients not harboring driver mutations could benefit from the combined therapy. The identification of predictive biomarkers before or short after initiation of therapy is therefore paramount for proper patient selection, especially among EGFR wild-types...
March 30, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28357677/identification-of-a-novel-somatic-mutation-leading-to-allele-dropout-for-egfr-l858r-genotyping-in-non-small-cell-lung-cancer
#17
Helio A Costa, Joel W Neal, Carlos D Bustamante, James L Zehnder
OBJECTIVE: While PCR-based genotyping methods abound in molecular testing for lung cancer therapy, these approaches may not provide the robust sensitivity to detect accurate genotypes in a variable cancer genomic background. METHODS: Here, we describe a study of a clinical tumor specimen containing a novel somatic single nucleotide variant that caused allele drop-out in EGFR L858R genotyping, resulting in a false-negative interpretation and impacting patient clinical management...
March 29, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28356014/inhibition-of-egfr-signaling-by-n-cyclohexyl-2-1-phenylsulfonyl-piperidin-4-yl-acetamide
#18
Sensen Lin, Hang Li, Jun Yu, Luyong Zhang, Ming Yan, Hongyang Li, Xinxin Li, Shengtao Yuan, Li Sun
The epidermal growth factor receptor (EGFR) is a driver oncogene and specific blockade of EGFR has been shown to be an effective therapeutic approach against multiple human cancers. Here we employed the homogeneous time-resolved fluorescence (HTRF) technology to screen for new EGFR mediators. 4 hits (NDS-41107、NDS-41119、NDS-41111 and NDS-41126) were confirmed in a compound library of 8000 compounds, and the IC50 values were determined to be 15.45±2.25μM (NDS-41107), 6.16±0.88 μM (NDS-41119), 11.33±3...
March 27, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28342334/oncogene-addiction-in-non-small-cell-lung-cancer-focus-on-ros1-inhibition
#19
REVIEW
Francesco Facchinetti, Giulio Rossi, Emilio Bria, Jean-Charles Soria, Benjamin Besse, Roberta Minari, Luc Friboulet, Marcello Tiseo
Detection of molecular aberrations driving the biology and the clinical behavior of advanced non-small cell lung cancer (NSCLC) allows the adoption of specific therapeutic strategies dramatically impacting disease courses. Among these, ROS1 rearrangements are present in 1-2% of lung adenocarcinomas. Thanks to similarities between ALK and ROS1 oncogenes, lessons inferred from ALK can be applied to ROS1-positive NSCLC; nevertheless, disparities exist between diseases mastered by these two fusion genes. In the absence of more common genetic alterations detected in NSCLC (e...
March 12, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28340578/abcb1-and-abcg2-drug-transporters-are-differentially-expressed-in-non-small-cell-lung-cancers-nsclc-and-expression-is-modified-by-cisplatin-treatment-via-altered-wnt-signaling
#20
M Vesel, J Rapp, D Feller, E Kiss, L Jaromi, M Meggyes, G Miskei, B Duga, G Smuk, T Laszlo, I Karner, J E Pongracz
BACKGROUND: Lung cancer (LC) is still the most common cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all LC cases but is not a single entity. It is now accepted that, apart from the characteristic driver mutations, the unique molecular signatures of adeno- (AC) and squamous cell carcinomas (SCC), the two most common NSCLC subtypes should be taken into consideration for their management. Therapeutic interventions, however, frequently lead to chemotherapy resistance highlighting the need for in-depth analysis of regulatory mechanisms of multidrug resistance to increase therapeutic efficiency...
March 24, 2017: Respiratory Research
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