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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
#1
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
#2
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
#3
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 Osimertinib First Time in Patients Ascending Dose (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
#4
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
#5
Jia Zhong, Lei Li, Zhijie Wang, Hua Bai, Gai Fei, Jian Chunduan, Jun Zhao, Minglei Zhuo, Yuyang Wang, Shuhang Wang, Wanchun Zang, Meina Wu, Tongtong An, Guanhua Rao, Jie Wang
BACKGROUND: EGFR-TKIs have greatly improved the prognosis of lung adenocarcinoma. However, approximately 5%-10% lung adenocarcinoma patients with EGFR sensitive mutations have primary resistance to EGFR-TKIs treatment. The underlying mechanism is unknown. METHODS: This study used next-generation sequencing (NGS) to explore the mechanisms of primary resistance by analyzing 11 patients with primary resistance and 11 patients sensitive to EGFR-TKIs. NGS targeted sequencing was performed on the Illumina X platform for 483 cancer-related genes...
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28723866/a-case-of-resistance-to-tyrosine-kinase-inhibitor-therapy-small-cell-carcinoma-transformation-concomitant-with-plasma-genotyped-t790m-positivity
#8
Yanjun Xu, Zhiyu Huang, Lei Gong, Yun Fan
Although non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations are responsive to EGFR-tyrosine kinase inhibitors, drug resistances are always inevitable. The secondary somatic EGFR threonine-methionine substitution at position 790 (T790M) mutation accounts for ∼50% of acquired resistance mechanisms. Small cell lung cancer (SCLC) transformation is a relatively rare mechanism, but has recently attracted considerable attention. The coexistence of both the mechanisms in one patient is much more scarce in clinic...
July 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28723342/molecular-analysis-of-circulating-free-dna-from-lung-cancer-patients-in-routine-laboratory-practice-a-cross-platform-comparison-of-three-different-molecular-methods-for-mutation-detection
#9
Stephan Bartels, Sascha Persing, Britta Hasemeier, Elisa Schipper, Hans Kreipe, Ulrich Lehmann
Cell-free DNA (cfDNA), which is isolated from blood plasma, represents a noninvasive source for the detection of mutations conferring resistance against epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small-cell lung cancer patients. In advanced disease stages, performing regular biopsies is often not possible because of the general health condition of the patients. Furthermore, a biopsy of a single tumor lesion or metastasis may not reflect the heterogeneous genotype of the tumor and its metastases...
July 16, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28683123/reverse-epithelial-mesenchymal-transition-contributes-to-the-regain-of-drug-sensitivity-in-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer-cells
#10
An-Fu Lee, Man-Chin Chen, Chao-Ju Chen, Chih-Jen Yang, Ming-Shyang Huang, Yu-Peng Liu
Tyrosine kinase inhibitors (TKIs) are currently the first-line treatment for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. These patients receive platinum-based chemotherapy as the second-line treatment after they develop resistance to TKIs. Many patients regain sensitivity to the TKIs used in the first-line treatment after the failure of chemotherapy. However, the molecular mechanism for the regain of TKI sensitivity is largely unknown. In this study, we established gefitinib-resistant PC9 and HCC827 cell lines, which did not harbor the EGFR T790M mutation and MET amplification but exhibited the epithelial-mesenchymal transition (EMT) phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28620690/acquired-resistance-to-erlotinib-in-egfr-mutation-positive-lung-adenocarcinoma-among-hispanics-clicap
#11
Andrés F Cardona, Oscar Arrieta, Martín Ignacio Zapata, Leonardo Rojas, Beatriz Wills, Noemí Reguart, Niki Karachaliou, Hernán Carranza, Carlos Vargas, Jorge Otero, Pilar Archila, Claudio Martín, Luis Corrales, Mauricio Cuello, Carlos Ortiz, Luis E Pino, Rafael Rosell, Zyanya Lucia Zatarain-Barrón
BACKGROUND: Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. PATIENTS AND METHODS: EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015...
August 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28606923/detection-of-driver-and-resistance-mutations-in-leptomeningeal-metastases-of-nsclc-by-next-generation-sequencing-of-cerebrospinal-fluid-circulating-tumor-cells
#12
Ben-Yuan Jiang, Yang-Si Li, Wei-Bang Guo, Xu-Chao Zhang, Zhi-Hong Chen, Jian Su, Wen-Zhao Zhong, Xue-Ning Yang, Jin-Ji Yang, Yang Shao, Biao Huang, Yan-Hui Liu, Qing Zhou, Hai-Yan Tu, Hua-Jun Chen, Zhen Wang, Chong-Rui Xu, Bin-Chao Wang, Shu-Yu Wu, Cun-Yi Gao, Xian Zhang, Yi-Long Wu
Purpose: Leptomeningeal metastases are more common in non-small cell lung cancer (NSCLC) with EGFR mutations. The diagnosis is difficult by traditional imaging only, and leads to poor understanding of resistance mechanisms of leptomeningeal metastases.Experimental Design: We compared the CellSearch Assay, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected leptomeningeal metastases. Next-generation sequencing that included 416 cancer-associated genes was also performed on cerebrospinal fluid circulating tumor cells (CSFCTC) of 19 patients...
June 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28599309/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#13
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...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28576746/a-higher-proportion-of-the-egfr-t790m-mutation-may-contribute-to-the-better-survival-of-patients-with-exon-19-deletions-compared-with-those-with-l858r
#14
E-E Ke, Qing Zhou, Qiu-Yi Zhang, Jian Su, Zhi-Hong Chen, Xu-Chao Zhang, Chong-Rui Xu, Jin-Ji Yang, Hai-Yan Tu, Hong-Hong Yan, Yi-Chen Zhang, Fei-Yu Niu, Yi-Long Wu
INTRODUCTION: Increasing evidence has demonstrated that exon 19 deletions (Del19) and L858R mutation in EGFR have different prognostic and predictive roles in NSCLC. We aimed to investigate whether these two mutations produced differences in mechanisms of resistance to EGFR tyrosine kinase inhibitors. METHODS: Consecutive patients with advanced EGFR-mutant NSCLC who acquired resistance to EGFR tyrosine kinase inhibitors and underwent postprogression biopsy were enrolled...
May 30, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28575795/-11-c-erlotinib-pet-cannot-detect-acquired-erlotinib-resistance-in-nsclc-tumor-xenografts-in-mice
#15
Alexander Traxl, Taraneh Beikbaghban, Thomas Wanek, Kushtrim Kryeziu, Christine Pirker, Severin Mairinger, Johann Stanek, Thomas Filip, Michael Sauberer, Claudia Kuntner, Walter Berger, Oliver Langer
INTRODUCTION: [(11)C]Erlotinib PET has shown promise to distinguish non-small cell lung cancer (NSCLC) tumors harboring the activating epidermal growth factor receptor (EGFR) mutation delE746-A750 from tumors with wild-type EGFR. To assess the suitability of [(11)C]erlotinib PET to detect the emergence of acquired erlotinib resistance in initially erlotinib-responsive tumors, we performed in vitro binding and PET experiments in mice bearing tumor xenografts using a range of different cancer cells, which were erlotinib-sensitive or exhibited clinically relevant resistance mechanisms to erlotinib...
September 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28572531/egfr-g796d-mutation-mediates-resistance-to-osimertinib
#16
Di Zheng, Min Hu, Yu Bai, Xuehua Zhu, Xuesong Lu, Chunyan Wu, Jiying Wang, Li Liu, Zheng Wang, Jian Ni, Zhenfan Yang, Jianfang Xu
Osimertinib is an effective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in multiple countries and regions for patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC). Despite impressive initial tumor responses, development of drug resistance ultimately limits the benefit of this compound. Mechanisms of resistance to osimertinib are just beginning to emerge, such as EGFR C797S and L718Q mutations, BRAF V600E and PIK3CA E545K mutations, as well as ERBB2 and MET amplification...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28539465/utility-of-genomic-assessment-of-blood-derived-circulating-tumor-dna-ctdna-in-patients-with-advanced-lung-adenocarcinoma
#17
Maria C Schwaederlé, Sandip P Patel, Hatim Husain, Megumi Ikeda, Richard B Lanman, Kimberly C Banks, AmirAli Talasaz, Lyudmila Bazhenova, Razelle Kurzrock
Purpose: Genomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with non-small cell lung adenocarcinoma (NSCLC) were ascertained and correlated with clinical characteristics and therapeutic outcomes.Experimental Design: Comprehensive plasma ctDNA testing was performed in 88 consecutive patients; 34 also had tissue next-generation sequencing; 29, other forms of genotyping; and 25 (28.4%) had no tissue molecular tests because of inadequate tissue or biopsy contraindications.Results: Seventy-two patients (82%) had ≥1 ctDNA alteration(s); among these, 75% carried alteration(s) potentially actionable by FDA-approved (61...
September 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28521430/reduced-expression-levels-of-pten-are-associated-with-decreased-sensitivity-of-hcc827-cells-to-icotinib
#18
Yang Zhai, Yanjun Zhang, Kejun Nan, Xuan Liang
The clinical resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been linked to EGFR T790M resistance mutations or MET amplifications. Additional mechanisms underlying EGFR-TKI drug resistance remain unclear. The present study demonstrated that icotinib significantly inhibited the proliferation and increased the apoptosis rate of HCC827 cells; the cellular mRNA and protein expression levels of phosphatase and tensin homolog (PTEN) were also significantly downregulated...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515244/what-when-and-how-of-biomarker-testing-in-non-small-cell-lung-cancer
#19
Gregory L Riely
Biomarker testing is recommended for all patients diagnosed with non-small cell lung cancer. At a minimum, testing should include the mutations/fusions EGFR, ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA-approved therapies are available for these alterations. Other actionable molecular findings include RET rearrangements, BRAF(V600E) mutations, and MET exon 14 alterations. If adequate testing was not performed at treatment initiation, molecular testing should be performed before administration of subsequent lines of therapy...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28469968/the-selective-c-met-inhibitor-tepotinib-can-overcome-epidermal-growth-factor-receptor-inhibitor-resistance-mediated-by-aberrant-c-met-activation-in-nsclc-models
#20
Manja Friese-Hamim, Friedhelm Bladt, Giuseppe Locatelli, Uz Stammberger, Andree Blaukat
Non-small cell lung cancer (NSCLC) sensitive to first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often acquires resistance through secondary EGFR mutations, including the T790M mutation, aberrant c-Met receptor activity, or both. We assessed the ability of the highly selective c-Met inhibitor tepotinib to overcome EGFR TKI resistance in various xenograft models of NSCLC. In models with EGFR-activating mutations and low c-Met expression (patient explant-derived LU342, cell line PC-9), EGFR TKIs caused tumors to shrink, but growth resumed upon cessation of treatment...
2017: American Journal of Cancer Research
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