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https://www.readbyqxmd.com/read/29163842/real-world-experience-of-afatinib-as-a-first-line-therapy-for-advanced-egfr-mutation-positive-lung-adenocarcinoma
#1
Sheng-Kai Liang, Min-Shu Hsieh, Meng-Rui Lee, Li-Ta Keng, Jen-Chung Ko, Jin-Yuan Shih
We evaluated the real-world efficacy and side effects of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. The medical records of patients receiving afatinib as a first-line therapy after National Health Insurance reimbursement between May 2014 and January 2016 were reviewed, and information on patient characteristics and treatment courses were collected consecutively. Rebiopsy tissue was collected for EGFR mutation and MET amplification analyses. MET amplification was detected by fluorescence in situ hybridization and immunohistochemistry...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29125233/in-vivo-imaging-xenograft-models-for-the-evaluation-of-anti-brain-tumor-efficacy-of-targeted-drugs
#2
Kenji Kita, Sachiko Arai, Akihiro Nishiyama, Hirokazu Taniguchi, Koji Fukuda, Rong Wang, Tadaaki Yamada, Shinji Takeuchi, Shoichiro Tange, Atsushi Tajima, Mitsutoshi Nakada, Kazuo Yasumoto, Yoshiharu Motoo, Takashi Murakami, Seiji Yano
Molecular-targeted drugs are generally effective against tumors containing driver oncogenes, such as EGFR, ALK, and NTRK1. However, patients harboring these oncogenes frequently experience a progression of brain metastases during treatment. Here, we present an in vivo imaging model for brain tumors using human cancer cell lines, including the EGFR-L858R/T790M-positive H1975 lung adenocarcinoma cells, the NUGC4 hepatocyte growth factor (HGF)-dependent gastric cancer cells, and the KM12SM colorectal cancer cells containing the TPM3-NTRK1 gene fusion...
November 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29119113/increased-egfr-phosphorylation-correlates-with-higher-programmed-death-ligand-1-expression-analysis-of-tki-resistant-lung-cancer-cell-lines
#3
Kenichi Suda, Leslie Rozeboom, Koh Furugaki, Hui Yu, Mary Ann C Melnick, Kim Ellison, Christopher J Rivard, Katerina Politi, Tetsuya Mitsudomi, Fred R Hirsch
Despite the recent development of immunotherapies that target programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) treatment, these therapies are less effective in NSCLC patients with epidermal growth factor receptor (EGFR) mutations. However, the molecular mechanisms underlying this lower efficacy of immunotherapies in EGFR mutant lung cancers are still unclear. In this study, we analyzed PD-L1 protein expression in lung cancer cell lines with EGFR mutations prior to and after acquisition of resistance to EGFR tyrosine kinase inhibitors (TKIs)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29117310/sequencing-and-phasing-cancer-mutations-in-lung-cancers-using-a-long-read-portable-sequencer
#4
Ayako Suzuki, Mizuto Suzuki, Junko Mizushima-Sugano, Martin C Frith, Wojciech Makalowski, Takashi Kohno, Sumio Sugano, Katsuya Tsuchihara, Yutaka Suzuki
Here, we employed cDNA amplicon sequencing using a long-read portable sequencer, MinION, to characterize various types of mutations in cancer-related genes, namely, EGFR, KRAS, NRAS and NF1. For homozygous SNVs, the precision and recall rates were 87.5% and 91.3%, respectively. For previously reported hotspot mutations, the precision and recall rates reached 100%. The precise junctions of EML4-ALK, CCDC6-RET and five other gene fusions were also detected. Taking advantages of long-read sequencing, we conducted phasing of EGFR mutations and elucidated the mutational allelic backgrounds of anti-tumor drug-sensitive and resistant mutations, which could provide useful information for selecting therapeutic approaches...
June 27, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29110101/histological-transformation-after-acquired-resistance-to-epidermal-growth-factor-tyrosine-kinase-inhibitors
#5
REVIEW
Yi Shao, Dian-Sheng Zhong
Non-small-cell lung cancer patients with sensitive epidermal growth factor receptor mutations generally respond well to tyrosine kinase inhibitors (TKIs). However, acquired resistance will eventually develop place after 8-16 months. Several mechanisms contribute to the resistance including T790M mutation, c-Met amplification, epithelial mesenchymal transformation and PIK3CA mutation; however, histological transformation is a rare mechanism. The patterns and mechanisms underlying histological transformation need to be explored...
November 7, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29097733/discovery-of-targetable-genetic-alterations-in-advanced-non-small-cell-lung-cancer-using-a-next-generation-sequencing-based-circulating-tumor-dna-assay
#6
Helei Hou, Xiaonan Yang, Jinping Zhang, Zhe Zhang, Xiaomei Xu, Xiaoping Zhang, Chuantao Zhang, Dong Liu, Weihua Yan, Na Zhou, Hongmei Zhu, Zhaoyang Qian, Zhuokun Li, Xiaochun Zhang
Next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) assays have provided a new method of identifying tumor-driving genes in patients with advanced non-small cell lung carcinoma (NSCLC), especially in those whose cancer tissues are unavailable or in those that have acquired treatment resistance. Here, we describe a total of 119 patients with advanced EGFR-TKI-naive NSCLC and 15 EGFR-TKI-resistant patients to identify somatic SNVs, small indels, CNVs and gene fusions in 508 tumor-related genes...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29094453/uterine-metastasis-of-lung-adenocarcinoma-under-molecular-target-therapy-with-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-a-case-report-and-review-of-the-literature
#7
Mayu Shibata, Masato Shizu, Kazuko Watanabe, Akihiro Takeda
A 63-year-old woman presented with abnormal vaginal bleeding. Her disease history was significant, and included advanced lung adenocarcinoma with a deletion mutation in exon 19 of the epidermal growth factor receptor (EGFR) gene, which was managed by concurrent chemoradiotherapy, followed by molecular targeted therapy with tyrosine kinase inhibitors (TKIs) for a two-year period. Contrast-enhanced computed tomography showed the enlargement of a previously suspicious myoma node, with peripheral enhancement. Hemorrhagic necrosis was also observed on magnetic resonance imaging...
November 2, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/29071523/choroidal-metastasis-from-non-small-cell-lung-cancer-responsive-to-osimertinib-a-case-report-efficacy-of-a-third-generation-epidermal-growth-factor-tyrosine-kinase-inhibitor
#8
Morara Mariachiara, Ruatta Celeste, Foschi Federico, Balducci Nicole, Ciardella Antonio
PURPOSE: To report a case of a choroidal metastasis from a non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation, which responded to Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (TKI). BACKGROUND: First- and second-generation EGFR-TKis have been widely used for advanced NSCLC patients; however, acquired resistance to these inhibitors, as T790M mutation, could be present in resistant cases. Third-generation EGFR-TKis have emerged as potential therapeutics to overcome this resistance...
October 25, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/29070999/treatment-of-leptomeningeal-metastases-in-a-patient-with-non-small-cell-lung-cancer-harboring-egfr-t790m-mutation
#9
Hardy Niu, Junle Zhou, Harvinder Maan, Maurie Markman, Jiaxin Niu
BACKGROUND: Leptomeningeal metastasis (LM) is an uncommon complication in patients with solid tumors, associated with poor survival. However, LM appears to be more frequent in lung cancer patients with EGFR mutations, posing a unique clinical challenge to treating physicians. CASE PRESENTATION: We report the case of a 68-year-old Asian man with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, which was initially treated with gefitinib. He developed disease progression 1 year later...
September 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/29070957/egfr-t790m-revealing-the-secrets-of-a-gatekeeper
#10
REVIEW
Brian Ko, Daniel Paucar, Balazs Halmos
Non-small-cell lung cancers that harbor activating mutations in the EGFR gene represent an important molecularly defined subset of lung cancer. Despite dramatic initial responses with first- and second-generation EGFR-directed tyrosine-kinase inhibitors (TKIs) against these cancers, the development of a dominant and frequent resistance mechanism through a threonine-methionine amino acid substitution at position 790 (T790M) of EGFR has limited the long-term efficacy of these targeted therapies. This "gatekeeper" EGFR T790M alteration remains the only validated and relevant second-site resistance mutation for EGFR, allowing for focused research to understand and overcome EGFR T790M-mediated resistance...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29069959/the-liquid-biopsy-a-tool-for-a-combined-diagnostic-and-theranostic-approach-for-care-of-a-patient-with-late-stage-lung-carcinoma-presenting-with-bilateral-ocular-metastases
#11
Linda Bouhlel, Véronique Hofman, Célia Maschi, Marius Ilié, Maryline Allégra, Charles-Hugo Marquette, Clarisse Audigier-Valette, Juliette Thariat, Paul Hofman
Liquid biopsies (LB) are used routinely in clinical practice in two situations for late stage non-small-cell lung cancer (NSCLC) patients, (i) at the initial diagnosis when looking for activating mutations in EGFR in the absence of analyzable tissue DNA and, (ii) during tumor progression on a tyrosine kinase inhibitor treatment to look for the resistance mutation T790M in EGFR. LB is not presently recommended in daily practice for the diagnosis of NSCLC. Areas covered: We report the diagnosis of a NSCLC in a patient with bilateral ocular metastases after detection of a deletion in exon 19 of EGFR when using plasma DNA...
November 2, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28965727/proteome-wide-map-of-targets-of-t790m-egfr-directed-covalent-inhibitors
#12
Sherry Niessen, Melissa M Dix, Sabrina Barbas, Zachary E Potter, Shuyan Lu, Oleg Brodsky, Simon Planken, Douglas Behenna, Chau Almaden, Ketan S Gajiwala, Kevin Ryan, RoseAnn Ferre, Michael R Lazear, Matthew M Hayward, John C Kath, Benjamin F Cravatt
Patients with non-small cell lung cancers that have kinase-activating epidermal growth factor receptor (EGFR) mutations are highly responsive to first- and second-generation EGFR inhibitors. However, these patients often relapse due to a secondary, drug-resistant mutation in EGFR whereby the gatekeeper threonine is converted to methionine (T790M). Several third-generation EGFR inhibitors have been developed that irreversibly inactivate T790M-EGFR while sparing wild-type EGFR, thus reducing epithelium-based toxicities...
November 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28961841/dual-met-and-erbb-inhibition-overcomes-intratumor-plasticity-in-osimertinib-resistant-advanced-non-small-cell-lung-cancer-nsclc
#13
A Martinez-Marti, E Felip, J Matito, E Mereu, A Navarro, S Cedrés, N Pardo, A Martinez de Castro, J Remon, J M Miquel, A Guillaumet-Adkins, E Nadal, G Rodriguez-Esteban, O Arqués, R Fasani, P Nuciforo, H Heyn, A Villanueva, H G Palmer, A Vivancos
Background: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib are the last line of targeted treatment of metastatic non-small-cell lung cancer (NSCLC) EGFR-mutant harboring T790M. Different mechanisms of acquired resistance to third-generation EGFR-TKIs have been proposed. It is therefore crucial to identify new and effective strategies to overcome successive acquired mechanisms of resistance. Methods: For Amplicon-seq analysis, samples from the index patient (primary and metastasis lesions at different timepoints) as well as the patient-derived orthotopic xenograft tumors corresponding to the different treatment arms were used...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28919784/durable-complete-remission-of-poor-performance-status-metastatic-lung-adenocarcinoma-patient-treated-with-second-line-erlotinib-a-case-report
#14
Dragana Jovanovic, Ruza Stevic, Marta Velinovic, Milica Kontic, Dragana Maric, Jelena Spasic, Davorin Radosavljevic
This paper presents a rare case of an elderly patient treated with erlotinib for disseminated lung adenocarcinoma with poor performance status (Eastern Cooperative Oncology Group performance status [PS]3). This treatment led to a long duration of complete remission according to Response Evaluation Criteria in Solid Tumors 1.1 - almost 7 years (81 months) of progression-free survival (PFS) and overall survival (OS) of 10 years by March 2017. The treatment with erlotinib started in September 2008 and it was well tolerated with no adverse effects...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28915640/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#15
Shu-Yan Han, Wei Zhao, Hai-Bo Han, Hong Sun, Dong Xue, Yan-Na Jiao, Xi-Ran He, Shan-Tong Jiang, Ping-Ping Li
Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28841389/osimertinib-as-first-line-treatment-of-egfr-mutation-positive-advanced-non-small-cell-lung-cancer
#16
Suresh S Ramalingam, James C-H Yang, Chee Khoon Lee, Takayasu Kurata, Dong-Wan Kim, Thomas John, Naoyuki Nogami, Yuichiro Ohe, Helen Mann, Yuri Rukazenkov, Serban Ghiorghiu, Daniel Stetson, Aleksandra Markovets, J Carl Barrett, Kenneth S Thress, Pasi A Jänne
Purpose The AURA study ( ClinicalTrials.gov identifier: NCT01802632) included two cohorts of treatment-naïve patients to examine clinical activity and safety of osimertinib (an epidermal growth factor receptor [EGFR] -tyrosine kinase inhibitor selective for EGFR-tyrosine kinase inhibitor sensitizing [ EGFRm] and EGFR T790M resistance mutations) as first-line treatment of EGFR-mutated advanced non-small-cell lung cancer (NSCLC). Patients and Methods Sixty treatment-naïve patients with locally advanced or metastatic EGFRm NSCLC received osimertinib 80 or 160 mg once daily (30 patients per cohort)...
August 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28829429/establishing-dual-resistance-to-egfr-tki-and-met-tki-in-lung-adenocarcinoma-cells-in-vitro-with-a-2-step-dose-escalation-procedure
#17
Toshimitsu Yamaoka, Motoi Ohba, Satoru Arata, Tohru Ohmori
Drug resistance is a major challenge in cancer therapy. The generation of resistant sublines in vitro is necessary for discovering novel mechanisms to overcome this challenge. Here, a 2-step dose-escalation method for establishing dual-resistance to an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), gefitinib, and a MET-TKI, PHA665752, is described. This method is based on simple stepwise dose-escalation of inhibitors for inducing acquired resistance in cell lines. The alternate method for generating resistant sublines involves exposing the cells to high concentrations of the inhibitor in one step...
August 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28818608/potential-resistance-mechanisms-revealed-by-targeted-sequencing-from-lung-adenocarcinoma-patients-with-primary-resistance-to-epidermal-growth-factor-receptor-egfr-tyrosine-kinase-inhibitors-tkis
#18
Jia Zhong, Lei Li, Zhijie Wang, Hua Bai, Fei Gai, Jianchun Duan, Jun Zhao, Minglei Zhuo, Yuyan Wang, Shuhang Wang, Wanchun Zang, Meina Wu, Tongtong An, Guanhua Rao, Guanshan Zhu, Jie Wang
INTRODUCTION: EGFR tyrosine kinase inhibitors (TKIs) have greatly improved the prognosis of lung adenocarcinoma. However, approximately 5% to 10% of patients with lung adenocarcinoma with EGFR sensitive mutations have primary resistance to EGFR TKI treatment. The underlying mechanism is unknown. METHODS: This study used next-generation sequencing to explore the mechanisms of primary resistance by analyzing 11 patients with primary resistance and 11 patients sensitive to EGFR TKIs...
August 14, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28782530/chemotherapeutics-resistance-arms-race-an-update-on-mechanisms-involved-in-resistance-limiting-egfr-inhibitors-in-lung-cancer
#19
REVIEW
Pankaj Kumar Singh, Om Silakari
Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc...
October 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28767414/real-world-experience-of-afatinib-as-a-first-line-therapy-for-advanced-egfr-mutation-positive-lung-adenocarcinoma
#20
Sheng-Kai Liang, Min-Shu Hsieh, Meng-Rui Lee, Li-Ta Keng, Jen-Chung Ko, Jin-Yuan Shih
We evaluated the real-world efficacy and side effects of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. The medical records of patients receiving afatinib as a first-line therapy after National Health Insurance reimbursement between May 2014 and January 2016 were reviewed, and information on patient characteristics and treatment courses were collected consecutively. Rebiopsy tissue was collected for EGFR mutation and MET amplification analyses. MET amplification was detected by fluorescence in situ hybridization and immunohistochemistry...
July 26, 2017: Oncotarget
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