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met exon 14

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https://www.readbyqxmd.com/read/28061541/a-prospective-multicenter-phase-ii-trial-of-low-dose-erlotinib-as-maintenance-treatment-after-platinum-doublet-chemotherapy-for-advanced-non-small-cell-lung-cancer-harboring-egfr-mutation
#1
Satoshi Hirano, Go Naka, Yuichiro Takeda, Motoyasu Iikura, Noriko Hayama, Asako Yanagisawa, Hiroyuki Amano, Makoto Nakamura, Sukeyuki Nakamura, Hiroshi Tabeta, Haruhito Sugiyama
BACKGROUND: Maintenance therapy with full-dose erlotinib for patients with advanced non-small cell lung cancer (NSCLC) has demonstrated a significant overall survival (OS) benefit. However, 150 mg/day of erlotinib seems too toxic as maintenance therapy. This study aimed to evaluate the efficacy and safety of low-dose erlotinib (25 mg/day) as maintenance treatment after platinum doublet chemotherapy in NSCLC harboring epidermal growth factor receptor (EGFR) mutation. METHODS: Activated EGFR-mutation-positive NSCLC patients who did not progress after first-line platinum-doublet chemotherapy, ≥20 and ≤85 years old, with performance status (PS) 0-3 were included in this study...
December 2016: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28024701/a-comprehensive-analysis-of-clinical-outcomes-in-lung-cancer-patients-harboring-a-met-exon-14-skipping-mutation-compared-to-other-driver-mutations-in-an-east-asian-population
#2
Chien-Hung Gow, Min-Shu Hsieh, Shang-Gin Wu, Jin-Yuan Shih
INTRODUCTION: Recurrent somatic splice-site alterations at MET exon 14 (MET(Δ14)), which result in exon skipping and MET proto-oncogene, receptor tyrosine kinase (MET) activation, have been characterised. However, their demographic features and clinical outcomes in East Asian lung cancer patients have yet to be determined. METHODS: A one-step reverse transcription-polymerase chain reaction (RT-PCR), using RNA samples from 850 East Asian lung cancer patients, was performed in order to detect MET(Δ14) and five other major driver mutations, including those in the EGFR, KRAS, ALK, HER2, and ROS1 genes...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28024693/the-race-to-target-met-exon-14-skipping-alterations-in-non-small-cell-lung-cancer-the-why-the-how-the-who-the-unknown-and-the-inevitable
#3
REVIEW
Thanyanan Reungwetwattana, Ying Liang, Viola Zhu, Sai-Hong Ignatius Ou
A number of small molecule tyrosine kinase inhibitors (TKIs) have now been approved for the treatment of non-small cell lung cancers (NSCLC), including those targeted against epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1. Despite a wealth of agents developed to target the receptor tyrosine kinase, MET, clinical outcomes have as yet been disappointing, leading to pessimism about the role of MET in the pathogenesis of NSCLC. However, in recent years, there has been a renewed interest in MET exon 14 alterations as potential drivers of lung cancer...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27988098/targeting-met-exon-14-skipping-alterations-has-lung-cancer-met-its-match
#4
EDITORIAL
Timothy A Yap, Sanjay Popat
No abstract text is available yet for this article.
January 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27987579/response-and-acquired-resistance-to-crizotinib-in-chinese-patients-with-lung-adenocarcinomas-harboring-met-exon-14-splicing-alternations
#5
Hua-Jie Dong, Peng Li, Chang-Ling Wu, Xiao-Yue Zhou, Hong-Jun Lu, Tong Zhou
Approximately 10% of lung adenocarcinomas harbor aberrations that are targetable using the approved multitargeted TKI crizotinib. MET exon 14 skipping mutation predicts for response to crizotinib in human lung adenocarcinomas. However, a substantial part of patients still has no sufficient tissue to perform genomic analysis. As a promising noninvasive biomarker and potential surrogate for the entire tumor genome, circulating tumor DNA (ctDNA) has been applied to the detection of driver gene mutations. Here we described the MET exon 14 splicing mutations in cell-free circulating-tumor DNA by next-generation sequencing (NGS) technology...
December 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27969534/ps01-67-case-series-of-met-exon-14-skipping-mutation-positive-non-small-cell-lung-cancers-and-response-to-crizotinib-topic-medical-oncology
#6
Samantha X Wang, Bing M Zhang, Heather Wakelee, Maximilian Diehn, Christian A Kunder, Joel W Neal
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27928797/-changes-of-diagnosis-and-treatment-for-gastrointestinal-stromal-tumors-during-a-18-year-period-in-four-medical-centers-of-china
#7
Haibo Qiu, Peng Zhang, Xingyu Feng, Tao Chen, Xiaowei Sun, Jiang Yu, Zhijing Chen, Yong Li, Kaixiong Tao, Guoxin Li, Zhiwei Zhou
OBJECTIVE: To elucidate the historic and current diagnosis and treatment status of gastrointestinal stromal tumor (GIST) in the Chinese population based on four high volume databases. METHODS: Clinicopathological data of GIST patients with follow-up information between January 1998 and December 2015 from Sun Yat-sen University Cancer Center, Union Hospital of Huazhong University of Science and Technology, Southern Medical University Nanfang Hospital and Guangdong General Hospital were retrospectively analyzed...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27899992/beside-p53-and-pten-identification-of-molecular-alterations-of-the-ras-mapk-and-pi3k-akt-signaling-pathways-in-high-grade-serous-ovarian-carcinomas-to-determine-potential-novel-therapeutic-targets
#8
Shuhui Chen, Elisa Cavazza, Catherine Barlier, Julia Salleron, Pierre Filhine-Tresarrieu, Céline Gavoilles, Jean-Louis Merlin, Alexandre Harlé
Despite great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify 'druggable' targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27864688/detection-of-mutations-in-the-braf-gene-in-patients-with-kit-and-pdgfra-wild-type-gastrointestinal-stromal-tumors
#9
Karin Jasek, Veronika Buzalkova, Gabriel Minarik, Andrea Stanclova, Peter Szepe, Lukas Plank, Zora Lasabova
Gastrointestinal stromal tumors (GISTs) are characterized by mutations in exons 9, 11, 13, and 17 of KIT or exons 12, 14, and 18 of PDGFRA gene. However, approximately 10 to 15 % of GISTs lack the mutations in KIT and PDGFRA, and these are referred to as wild-type GISTs which are less sensitive to tyrosine-kinase inhibitors. The aim of this study was to detect BRAF mutations in patients with wild-type GISTs. We applied a sensitive allele-specific PCR, which was optimized using the V600E mutation-harboring cell line RKO, followed by verification of the results by dideoxy sequencing...
January 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27826534/fusion-gene-and-splice-variant-analyses-in-liquid-biopsies-of-lung-cancer-patients
#10
REVIEW
Cristina Aguado, Ana Giménez-Capitán, Niki Karachaliou, Ana Pérez-Rosado, Santiago Viteri, Daniela Morales-Espinosa, Rafael Rosell
Obtaining a biopsy of solid tumors requires invasive procedures that strongly limit patient compliance. In contrast, a blood extraction is safe, can be performed at many time points during the course disease and encourages appropriate therapy modifications, potentially improving the patient's clinical outcome and quality of life. Fusion of the tyrosine kinase genes anaplastic lymphoma kinase (ALK), C-ROS oncogen 1 (ROS 1), rearranged during transfection (RET) and neurotrophic tyrosine kinase 1 (NTRK1) occur in 1-5% of lung adenocarcinomas and constitute therapeutic targets for tyrosine kinase inhibitors...
October 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/27794501/targeting-met-in-lung-cancer-will-expectations-finally-be-met
#11
REVIEW
Alexander Drilon, Federico Cappuzzo, Sai-Hong Ignatius Ou, D Ross Camidge
The hepatocyte growth factor receptor (MET) is a potential therapeutic target in a number of cancers, including NSCLC. In NSCLC, MET pathway activation is thought to occur through a diverse set of mechanisms that influence properties affecting cancer cell survival, growth, and invasiveness. Preclinical and clinical evidence suggests a role for MET activation as both a primary oncogenic driver in subsets of lung cancer and as a secondary driver of acquired resistance to targeted therapy in other genomic subsets...
January 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27745897/-interest-of-crizotinib-in-a-lung-cancer-patient-with-de-novo-amplification-of-met
#12
A Rabeau, I Rouquette, J-M Vantelon, E Taranchon-Clermont, J Mazières
Targeted therapy in lung cancer changes the prognostic and treatment of patients. MET is an oncogene including exon 14 mutations and gene amplification associated with worse prognosis. We here report the case of a 47-year-old former smoker, woman, with a stage IV lung adenocarcinoma with multiple chemotherapy failure. A MET amplification was identified and the patient consequently received crizotinib. A major response was observed after eight weeks of treatment. MET amplification screening appears to be interesting with some oncogenic-addicted tumor response rate...
October 13, 2016: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/27732995/metastatic-lung-cancer-emerging-therapeutic-strategies
#13
Sana Saif Ur Rehman, Suresh S Ramalingam
Advanced stage nonsmall cell lung cancer had been treated mainly with platinum-based doublet chemotherapy, and other cytotoxic agents that offered significant survival advantage over best supportive care, until recently. Modest improvements were achieved with the addition of antibodies targeting the vascular endothelial growth factor, and the introduction of maintenance chemotherapy. Improvements in our knowledge of lung cancer biology have shifted the current treatment paradigm from being based on histology to one based on molecular biomarkers...
October 2016: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27693535/intracranial-activity-of-cabozantinib-in-met-exon-14-positive-nsclc-with-brain-metastases
#14
Samuel J Klempner, Ali Borghei, Behrooz Hakimian, Siraj M Ali, Sai-Hong Ignatius Ou
INTRODUCTION: A significant portion of NSCLCs with MET proto-oncogene, receptor tyrosine kinase gene (MET) exon 14 skipping alterations are sensitive to small-molecule mesenchymal-epithelial transition tyrosine kinase inhibitors. However, the incidence and management of brain metastases in this molecular subset is unknown and represents an unmet clinical need. METHODS: Hybrid capture-based comprehensive genomic profiling identified a patient with a MET exon 14 skipping alteration, and serial magnetic resonance imaging was utilized to follow intracranial disease during crizotinib and subsequent cabozantinib therapy...
January 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27676475/o-04-profiling-of-met-amplified-non-small-cell-lung-cancer-nsclc-correlation-to-cmet-protein-expression-met-exon-14-skipping
#15
David Arguello, Andreas Voss, Zoran Gatalica, Ryan Bender
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27666659/emergence-of-preexisting-met-y1230c-mutation-as-a-resistance-mechanism-to-crizotinib-in-nsclc-with-met-exon-14-skipping
#16
Sai-Hong Ignatius Ou, Lauren Young, Alexa B Schrock, Adrienne Johnson, Samuel J Klempner, Viola W Zhu, Vincent A Miller, Siraj M Ali
INTRODUCTION: MET proto-oncogene, receptor tyrosine kinase gene exon 14 skipping (METex14) alterations represent a unique subset of oncogenic drivers in NSCLC. Preliminary clinical activity of crizotinib against METex14-positive NSCLC has been reported. The full spectrum of resistance mechanisms to crizotinib in METex14-positive NSCLC remains to be identified. METHODS: Hybrid capture-based comprehensive genomic profiling performed on a tumor specimen obtained at diagnosis, and a hybrid capture-based assay of circulating tumor DNA (ctDNA) at the time of progression during crizotinib treatment was assessed in a pairwise fashion...
January 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27664533/responses-to-crizotinib-can-occur-in-high-level-met-amplified-non-small-cell-lung-cancer-independent-of-met-exon-14-alterations
#17
Rafael Caparica, Cheng Tzu Yen, Renata Coudry, Sai-Hong Ignatius Ou, Marileila Varella-Garcia, D Ross Camidge, Gilberto de Castro
Activation of the MET proto-oncogene (MET) highly sensitive to MET inhibition has recently been described in NSCLC through two mechanisms: high-level amplification of the MNNG HOS Transforming gene (MET) (usually expressed relative to the chromosome 7 centromere [CEP7] when using fluorescence in situ hybridization) and exon 14 alterations. As partial overlap of these biomarkers occurs, whether one is purely a surrogate for the other or both can represent true oncogenic driver states continues to be explored...
January 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27615396/comprehensive-characterization-of-oncogenic-drivers-in-asian-lung-adenocarcinoma
#18
Shiyong Li, Yoon-La Choi, Zhuolin Gong, Xiao Liu, Maruja Lira, Zhengyan Kan, Ensel Oh, Jian Wang, Jason C Ting, Xiangsheng Ye, Christoph Reinhart, Xiaoqiao Liu, Yunfei Pei, Wei Zhou, Ronghua Chen, Shijun Fu, Gang Jin, Awei Jiang, Julio Fernandez, James Hardwick, Min Woong Kang, Hoseok I, Hancheng Zheng, Jhingook Kim, Mao Mao
INTRODUCTION: The incidence rate of lung adenocarcinoma (LUAD), the predominant histological subtype of lung cancer, is elevated in Asians, particularly in female nonsmokers. The mutation patterns in LUAD in Asians might be distinct from those in LUAD in whites. METHODS: We profiled 271 resected LUAD tumors (mainly stage I) to characterize the genomic landscape of LUAD in Asians with a focus on female nonsmokers. RESULTS: Mutations in EGFR, KRAS, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), and BRAF; gene fusions involving anaplastic lymphoma receptor tyrosine kinase gene (ALK), ROS1, and ret proto-oncogene (RET); and Met Proto-Oncogene Tyrosine Kinase (MET) exon 14 skipping were the major drivers in LUAD in Asians, exhibiting mutually exclusive and differing prevalence from those reported in studies of LUAD in non-Asians...
December 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27565402/met-in-the-driver-s-seat-exon-14-skipping-mutations-as-actionable-targets-in-lung-cancer
#19
EDITORIAL
Martin Sattler, Ravi Salgia
No abstract text is available yet for this article.
September 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27550450/antitumor-properties-of-an-igg2-enhanced-next-generation-met-monoclonal-antibody-that-degrades-wild-type-and-mutant-met-receptors
#20
Yan Yang, Sreekala Mandiyan, Brett S Robinson, Gerald McMahon
A sound rationale exists for antibody targeting of the MET receptor tyrosine kinase, but therapeutic agents that can broadly block HGF ligand binding and exon 14-mutated or amplified MET to induce receptor degradation have yet to be reported. Here we report the identification of several MET monoclonal antibodies (mAb) that block MET-dependent signaling and tumor growth. In particular, the MET mAb KTN0073 and KTN0074 bind the Sema/PSI domain, at overlapping but distinct epitopes, preventing HGF interaction with MET and triggering receptor ubiquitination and degradation...
October 1, 2016: Cancer Research
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