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https://www.readbyqxmd.com/read/29621416/c-met-inhibitors-for-advanced-non-small-cell-lung-cancer
#1
Giulia Pasquini, Giuseppe Giaccone
The role of the c-mesenchymal-epithelial transition factor (c-MET) signaling pathway in tumor progression and invasion has been extensively studied. C-MET inhibitors have shown anti-tumor activity in NSCLC both in preclinical and in clinical trials. However, given the molecular heterogeneity of NSCLC, it is likely that only a specific subset of NSCLC patients will benefit from c-MET inhibitors. Emerging data also suggest that MET inhibitors in combination with EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors) may have a role in therapy for both EGFR-TKI resistant and EGFR-TKI naïve patients...
April 5, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29507487/standardizing-biomarker-testing-for-canadian-patients-with-advanced-lung-cancer
#2
B Melosky, N Blais, P Cheema, C Couture, R Juergens, S Kamel-Reid, M-S Tsao, P Wheatley-Price, Z Xu, D N Ionescu
Background: The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor ( EGFR ) inhibitors, is the standard of care in Canada and many parts of the world. Methods: A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR , anaplastic lymphoma kinase ( ALK ), ROS1 , BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression...
February 2018: Current Oncology
https://www.readbyqxmd.com/read/29489023/kras-mutation-is-predictive-of-outcome-in-patients-with-pulmonary-sarcomatoid-carcinoma
#3
Mitra Mehrad, Somak Roy, William A LaFramboise, Patti Petrosko, Caitlyn Miller, Pimpin Incharoen, Sanja Dacic
Pulmonary Sarcomatoid Carcinoma (PSC) is a poorly-differentiated non-small cell lung carcinoma (NSCLC) with aggressive behavior. This study aimed to evaluate the prognostic clinicopathologic and genetic characteristics of PSCs. Fifty-three cases of surgically treated PSCs were selected, of which 23 were subjected to mutation and copy number variation analysis using 50-gene Ion AmpliSeq Cancer Panel. Majority of the patients were male (32/53, 60.3%) and smoker (51/53, 96.2%). Overall, 25 (47.1%) patients died within 2 to 105 months (mean 22...
February 28, 2018: Histopathology
https://www.readbyqxmd.com/read/29467863/detection-of-egfr-and-braf-mutations-by-competitive-allele-specific-taqman-polymerase-chain-reaction-in-lung-adenocarcinoma
#4
Yang Yang, Yi Meng, Hang Zhang, Xiaoyan Shen, Rutian Li, Lixia Yu, Baorui Liu, Lifeng Wang
Epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitors are the standard first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) expressing sensitive EGFR-mutants. Other drugs target different driver mutants, including the serine/threonine-protein kinase B-raf (BRAF) inhibitor dabrafenib, which has exhibited promising efficacy for treating patients with metastatic BRAF-mutated NSCLC. Therefore, identifying patients carrying mutations that may be treated using targeted therapies is important...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456848/survival-associated-factors-of-first-line-egfr-tyrosine-kinase-inhibitor-responders-and-non-responders-in-lung-adenocarcinoma-patients-with-common-egfr-mutations
#5
Ming-Szu Hung, Yu-Hung Fang, Yu-Ching Lin, Jr-Hau Lung, Meng-Jer Hsieh, Ying-Huang Tsai
The aim of the present retrospective cohort study was to elucidate the clinical presentation of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) responders and non-responders in lung adenocarcinoma patients with common EGFR mutations. The cohort included 131 lung adenocarcinoma patients with common exon 19 or exon 21 EGFR mutations, who were receiving first-line EGFR-TKI therapy. The patient characteristics, treatment regimen and outcomes were recorded and analyzed. Of the 131 patients, 104 (79...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29435981/forty-nine-gastric-cancer-cell-lines-with-integrative-genomic-profiling-for-development-of-c-met-inhibitor
#6
Hyun Jeong Kim, Sun Kyoung Kang, Woo Sun Kwon, Tae Soo Kim, Inhye Jeong, Hei-Cheul Jeung, Michael Kragh, Ivan D Horak, Hyun Cheol Chung, Sun Young Rha
Receptor tyrosine kinase MET (c-MET) has received considerable attention as a potential target for gastric cancer (GC) therapy and a number of c-MET inhibitors have been developed. For successful drug development, proper preclinical studies especially using patient derived cancer cell lines are very important. We profiled MET and MET-related characteristics in 49 GC cell lines to utilize them as models in preclinical studies of GC. Forty-nine cell lines were analyzed for genetic, biological, and molecular status to characterize MET and MET-related molecules...
February 13, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29416799/correlation-among-genetic-variations-of-c-met-in-chinese-patients-with-non-small-cell-lung-cancer
#7
Jianchun Duan, Xiaodan Yang, Jun Zhao, Minglei Zhuo, Zhijie Wang, Tongtong An, Hua Bai, Jie Wang
Background: The purpose of our research was to determine the correlation of amplification, protein expression and somatic mutation of c-MET in IIIb-IV stage NSCLC (Non-small cell lung cancer). We also explored correlation of c-MET variation with clinical outcome. Results: c-MET expression was observed in 28.6% (56/196) cases, and among those 13.8% (27/196) were shown to be FISH positive. Only 2.67% patients in this study carried the c-MET mutation. Cases with c-MET FISH positive were all IHC positive ,but in IHC positive cases, only half were FISH positive...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29381967/responses-to-crizotinib-and-disease-monitoring-with-circulating-tumor-cells-in-lung-adenocarcinoma-patient-with-met-exon-14-skipping-mutation-a-case-report
#8
Xiang Tan, Lei Dai, Yongyong Wang, Guanbiao Liang, Nuo Yang, Mingwu Chen
RATIONALE: Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutation was a targetable alteration in nonsmall-cell lung cancer (NSCLC), and the MET inhibitor of crizotinib had the most efficacy among all the targeted drugs. Most of the cancer-related deaths are associated with metastasis. Circulating tumor cells (CTCs) have been a valuable biomarker in assessing metastasis. Recent experiences suggested that CTCs detection may help improve diagnosis and predict prognosis for patients with NSCLC...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29338938/distinct-met-protein-localization-associated-with-met-exon-14-mutation-types-in-patients-with-non-small-cell-lung-cancer
#9
Tian Qiu, Weihua Li, Tongtong Zhang, Puyuan Xing, Wenting Huang, Bingning Wang, Lixia Chu, Lei Guo, Xiuyun Liu, Yan Li, Jianming Ying, Junling Li
BACKGROUND: The MET gene has been recognized as a potential important therapeutic target in non-small-cell lung cancer (NSCLC). We sought to investigate the MET exon 14 mutations in a cohort of Chinese patients with NSCLC. METHODS: We tested 461 NSCLCs for MET exon 14 mutations by sequencing whole exon 14 and its flanking introns. The protein expression was determined by immunohistochemical analysis. RESULTS: In this study, we identified MET exon 14 mutations in 9 (2...
December 21, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29217198/clinical-molecular-and-computational-analysis-in-two-cases-with-mitochondrial-encephalomyopathy-associated-with-suclg1-mutation-in-a-consanguineous-family
#10
Marwa Maalej, Amel Tej, Jihène Bouguila, Samia Tilouche, Senda Majdoub, Boudour Khabou, Mouna Tabbebi, Rahma Felhi, Marwa Ammar, Emna Mkaouar-Rebai, Leila Keskes, Lamia Boughamoura, Faiza Fakhfakh
Deficiency of the mitochondrial enzyme succinyl COA ligase (SUCL) is associated with encephalomyopathic mtDNA depletion syndrome and methylmalonic aciduria. This disorder is caused by mutations in both SUCL subunits genes: SUCLG1 (α subnit) and SUCLA2 (β subnit). We report here, two Tunisian patients belonging to a consanguineous family with mitochondrial encephalomyopathy, hearing loss, lactic acidosis, hypotonia, psychomotor retardation and methylmalonic aciduria. Mutational analysis of SUCLG1 gene showed, for the first time, the presence of c...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29188469/met-targeting-antibody-emibetuzumab-and-kinase-inhibitor-merestinib-as-single-agent-or-in-combination-in-a-cancer-model-bearing-met-exon-14-skipping
#11
S Betty Yan, Suzane L Um, Victoria L Peek, Jennifer R Stephens, Wei Zeng, Bruce W Konicek, Ling Liu, Jason R Manro, Volker Wacheck, Richard A Walgren
Purpose Approximately 3% of lung cancer bears mutations leading to MET exon 14 skipping, an oncogenic driver which is further evidenced by case reports of patient response to MET kinase inhibitor treatment. Approximately 15% of tumors harboring MET exon14 skipping have concurrent MET amplification. Experimental Design Merestinib is a type II MET kinase inhibitor. Emibetuzumab, a bivalent anti-MET antibody, internalizes MET receptor. Each single agent and the combination were evaluated in the Hs746t gastric cancer line bearing MET exon14 skipping and MET amplification...
November 29, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29139039/genetic-screening-and-molecular-characterization-of-met-alterations-in-non-small-cell-lung-cancer
#12
M Saigi, A McLeer-Florin, E Pros, E Nadal, E Brambilla, M Sanchez-Cespedes
PURPOSE: Aberrant activation of MET as a result of exon 14-skipping (METex14) mutations or gene amplification is an oncogenic mechanism in non-small cell lung carcinoma (NSCLC) and a potential therapeutic target. The purpose of this study was to characterize MET alterations in a cohort of NSCLC patients treated with surgery. METHODS AND PATIENTS: 157 NSCLCs of various histopathologies, including pulmonary sarcomatoid carcinomas (PSC), were tested for MET alterations...
November 14, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29066084/comparative-genomic-profiling-of-matched-primary-and-metastatic-tumors-in-renal-cell-carcinoma
#13
Maria F Becerra, Ed Reznik, Almedina Redzematovic, Daniel M Tennenbaum, Mahyar Kashan, Mazyar Ghanaat, Jozefina Casuscelli, Brandon Manley, Philip Jonsson, Renzo G DiNatale, Kyle A Blum, Jeremy C Durack, Stephen B Solomon, Maria E Arcila, Caitlin Bourque, Nick Socci, Maria I Carlo, Chung-Han Lee, Martin H Voss, Darren R Feldman, Robert J Motzer, Jonathan A Coleman, Paul Russo, Emily H Cheng, A Ari Hakimi, James J Hsieh
BACKGROUND: Next-generation sequencing (NGS) studies of matched pairs of primary and metastatic tumors in renal cell carcinoma (RCC) have been limited to small cohorts. OBJECTIVE: To evaluate the discordance in somatic mutations between matched primary and metastatic RCC tumors. DESIGN, SETTING, AND PARTICIPANTS: Primary tumor (P), metastasis (M), and germline DNA from 60 patients with RCC was subjected to NGS with a targeted exon capture-based assay of 341 cancer-associated genes...
October 20, 2017: European Urology Focus
https://www.readbyqxmd.com/read/29063069/targeting-met-in-cancer-therapy
#14
REVIEW
Hong-Nan Mo, Peng Liu
MET encodes a receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF). The specific combination of c-MET and HGF activates downstream signaling pathways to trigger cell migration, proliferation, and angiogenesis. MET exon 14 alterations and MET gene amplification play a critical role in the origin of cancer. Several monoclonal antibodies and small-molecule inhibitors of c-MET have been evaluated in clinical trials. In patients with advanced non-small cell lung cancer, cabozantinib and crizotinib showed clear efficacy with a generally tolerable adverse events profile...
September 2017: Chronic Diseases and Translational Medicine
https://www.readbyqxmd.com/read/29037218/clinicopathologic-features-and-treatment-efficacy-of-chinese-patients-with-braf-mutated-metastatic-colorectal-cancer-a-retrospective-observational-study
#15
Xicheng Wang, Qing Wei, Jing Gao, Jian Li, Jie Li, Jifang Gong, Yanyan Li, Lin Shen
BACKGROUND: The prognostic role of the V600E mutation of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in metastatic colorectal cancer (mCRC) is well established, but the therapeutic regimen targeting this disease is lacking. This study aimed to analyze the clinicopathologic features of and treatment efficacy of commonly used regimens on BRAF-mutated mCRCs. METHODS: We collected and reviewed the medical records of mCRC patients treated at Peking University Cancer Hospital & Institute (Beijing, China) between July 2011 and July 2016...
October 16, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28960774/the-bdnf-val66met-polymorphism-is-associated-with-lower-bmi-lower-postprandial-glucose-levels-and-elevated-carbohydrate-intake-in-children-and-adolescents
#16
A Kalenda, K Landgraf, D Löffler, P Kovacs, W Kiess, A Körner
BACKGROUND: The amino acid-changing exonic variant rs6265 (Val66Met polymorphism) in the brain-derived neurotrophic factor (BDNF) has been linked to obesity in several genotype-phenotype association studies. OBJECTIVE: To identify metabolic factors by which this effect might be conveyed, we aimed to investigate its correlation with (i) obesity, (ii) metabolic parameters, (iii) serum levels of BDNF and (iv) measures of energy intake in children and adolescents. METHODS: We genotyped the variant in 2131 subjects (age 6-18 years) and checked for an association with obesity...
March 2018: Pediatric Obesity
https://www.readbyqxmd.com/read/28958502/dacomitinib-versus-gefitinib-as-first-line-treatment-for-patients-with-egfr-mutation-positive-non-small-cell-lung-cancer-archer-1050-a-randomised-open-label-phase-3-trial
#17
RANDOMIZED CONTROLLED TRIAL
Yi-Long Wu, Ying Cheng, Xiangdong Zhou, Ki Hyeong Lee, Kazuhiko Nakagawa, Seiji Niho, Fumito Tsuji, Rolf Linke, Rafael Rosell, Jesus Corral, Maria Rita Migliorino, Adam Pluzanski, Eric I Sbar, Tao Wang, Jane Liang White, Sashi Nadanaciva, Rickard Sandin, Tony S Mok
BACKGROUND: Dacomitinib is a second-generation, irreversible EGFR tyrosine kinase inhibitor. We compared its efficacy and safety with that of the reversible EGFR tyrosine kinase inhibitor gefitinib in the first-line treatment of patients with advanced EGFR-mutation-positive non-small-cell lung cancer (NSCLC). METHODS: In this international, multicentre, randomised, open-label, phase 3 study (ARCHER 1050), we enrolled adults (aged ≥18 years or ≥20 years in Japan and South Korea) with newly diagnosed advanced NSCLC and one EGFR mutation (exon 19 deletion or Leu858Arg) at 71 academic medical centres and university hospitals in seven countries or special administrative regions...
November 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28952227/analysis-of-the-status-of-egfr-ros1-and-met-genes-in-non-small-cell-lung-adenocarcinoma
#18
Qiong Wang, Yali Lv, Mei Zhong, Fengwei Zhu, Lixin Wei, Huaiyin Shi
PURPOSE: To investigate the status and distribution of epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (MET), and receptor tyrosine kinase (ROS1) genes in patients with non-small cell lung (NSCL) adenocarcinoma. METHODS: The copy number of the MET gene was detected using fluorescence in situ hybridization (FISH). The splice mutation in exon 14 gene was detected by Sanger sequencing. The mutations in EGFR and the fusion of the ROS1 gene were detected using the fluorescence real-time quantitative PCR method (RT-qPCR)...
July 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28943896/a-large-chinese-pedigree-of-multiple-endocrine-neoplasia-type-2a-with-a-novel-c634y-d707e-germline-mutation-in-ret-exon-11
#19
Fanqian Lu, Xiaohong Chen, Yunlong Bai, Yaru Feng, Jian Wu
The present study identified the clinical features of the largest multiple endocrine neoplasia type 2 (MEN2) A pedigree from China, with a novel double missense rearranged during transfection (RET) mutation (C634Y/D707E). To the best of our knowledge, the D707E mutation has not been identified to date. In the present study, a total of 101 family members who originated from a large pedigree (134 members in total) underwent RET mutation screening by next-generation sequencing and polymerase chain reaction (PCR) amplification, followed by direct bidirectional DNA sequencing...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28843992/tracking-met-de-addiction-in-lung-cancer-a-road-towards-the-oncogenic-target
#20
REVIEW
S Pilotto, L Carbognin, N Karachaliou, P C Ma, R Rosell, G Tortora, E Bria
The discovery of druggable oncogenic drivers (i.e. EGFR and ALK), along with the introduction of comprehensive tumor genotyping techniques into the daily clinical practice define non-small-cell lung cancer (NSCLC) asa group of heterogeneous diseases, requiring a context-personalized clinico-therapeutical approach. Among the most investigated biomarkers, the MET proto-oncogene has been extensively demonstrated to play a crucial role throughout the lung oncogenesis, unbalancing the proliferation/apoptosis signaling and influencing the epithelial-mesenchymal transition and the invasive phenotype...
November 2017: Cancer Treatment Reviews
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