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https://www.readbyqxmd.com/read/29329944/use-of-superarms-egfr-mutation-detection-kit-to-detect-egfr-in-plasma-cell-free-dna-of-patients-with-lung-adenocarcinoma
#1
Shaohua Cui, Lin Ye, Huimin Wang, Tianqing Chu, Yizhuo Zhao, Aiqin Gu, Liwen Xiong, Chunlei Shi, Liyan Jiang
BACKGROUND: The SuperARMS EGFR Mutation Detection Kit (SuperARMS) is highly selective and sensitive and able to detect 41 of the most common somatic mutations in exons 18 to 21 of the epidermal growth factor receptor gene (EGFR). It allows for the detection of 0.2% to 0.8% mutant DNA in a background of 99.8% to 99.2% normal DNA. The present study assessed the performance of SuperARMS in detecting EGFR mutations in cell-free DNA (cfDNA) samples derived from plasma in patients with advanced lung adenocarcinoma...
December 21, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29325035/amplicon-based-next-generation-sequencing-of-plasma-cell-free-dna-for-detection-of-driver-and-resistance-mutations-in-advanced-non-small-cell-lung-cancer
#2
N Guibert, Y Hu, N Feeney, Y Kuang, V Plagnol, G Jones, K Howarth, J F Beeler, C P Paweletz, G R Oxnard
Background: Genomic analysis of plasma cell-free DNA is transforming lung cancer care, however available assays are limited by cost, turnaround time, and imperfect accuracy. Here we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). Methods: Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1 and other rare genotypes) were collected while on therapy and analyzed, blinded to tumor genotype...
January 9, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29321587/distribution-analysis-of-epertinib-in-brain-metastasis-of-her2-positive-breast-cancer-by-imaging-mass-spectrometry-and-prospect-for-antitumor-activity
#3
Yukari Tanaka, Michinari Hirata, Satomi Shinonome, Mikinori Torii, Ken-Ichi Nezasa, Hidekazu Tanaka
Epertinib (S-222611) is a potent, reversible, and selective tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), human EGFR2 (HER2), and human EGFR4. We developed experimental brain metastasis models by intraventricular injection (intraventricular injection mouse model; IVM) of HER2-positive breast cancer (MDA-MB-361-luc-BR2/BR3) or T790M-EGFR-positive lung cancer (NCI-H1975-luc) cells. After a single oral administration, epertinib and lapatinib concentrations in brain metastatic regions were analyzed by quantitative imaging mass spectrometry...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321093/a-retrospective-comparison-of-the-clinical-efficacy-of-gefitinib-erlotinib-and-afatinib-in-japanese-patients-with-non-small-cell-lung-cancer
#4
Atsushi Fujiwara, Masamichi Yoshida, Hajime Fujimoto, Hiroki Nakahara, Kentaro Ito, Kota Nishihama, Taro Yasuma, Osamu Hataji, Osamu Taguchi, Corina N D'Alessandro-Gabazza, Esteban C Gabazza, Tetsu Kobayashi
Tyrosine kinase inhibitors (TKIs) are very effective against non-small-cell lung cancer caused by epidermal growth factor receptor (EGFR) mutation. Before the approval of osimertinib in March 2016, there were only three available EGFR TKIs (gefitinib, erlotinib and afatinib) for the therapy of non-small-cell lung cancer in Japan. Osimertinib can be indicated only against T790M (+) lung cancer as a second-line therapy. However, whether gefitinib, erlotinib or afatinib is most appropriate as a first-line therapy is still a controversial issue...
January 10, 2018: Oncology Research
https://www.readbyqxmd.com/read/29299405/clinical-management-of-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer-patients-after-progression-on-previous-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-the-necessity-of-repeated-molecular-analysis
#5
REVIEW
José Luís González-Larriba, Martín Lázaro-Quintela, Manuel Cobo, Manuel Dómine, Margarita Majem, Rosario García-Campelo
One of the most important advances in the treatment of non-small cell lung cancer (NSCLC) has been the identification of molecular alterations vulnerable to targeted inhibition, such as mutations in the epidermal growth factor receptor (EGFR) gene. EGFR tyrosine kinase inhibitors (EGFR-TKIs) are targeted agents used to treat EGFR mutation-positive advanced NSCLC showing significant improvements in terms of response rate (RR) and progression-free survival (PFS) compared to conventional chemotherapy. However, all patients eventually develop resistance to first-line EGFR-TKIs...
December 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29299135/acquired-resistance-to-pi3k-mtor-inhibition-is-associated-with-mitochondrial-dna-mutation-and-glycolysis
#6
King Xin Koh, Gim Hwa Tan, Sarah Hong Hui Low, Mohd Feroz Mohd Omar, Min Ji Han, Barry Iacopetta, Ross Soo, Mounia Beloueche-Babari, Bhaskar Bhattacharya, Richie Soong
Acquired resistance (AQR) to drug treatment occurs frequently in cancer patients and remains an impediment to successful therapy. The aim of this study was to gain insight into how AQR arises following the application of PI3K/mTOR inhibitors. H1975 lung cancer cells with EGFR T790M mutations that confer resistance to EGFR inhibitors underwent prolonged treatment with the PI3K/mTOR inhibitor, BEZ235. Monoclonal cells with stable and increased resistance to BEZ235 were obtained after 8 months treatment. These AQR clones showed class-specific resistance to PI3K/mTOR inhibitors, reduced G1 cell cycle arrest and impedance of migration following PI3K/mTOR inhibition, reduced PTEN expression and increased Akt and S6RP phosphorylation...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296194/changes-in-pd-l1-expression-according-to-tumor-infiltrating-lymphocytes-of-acquired-egfr-tki-resistant-egfr-mutant-non-small-cell-lung-cancer
#7
Tae-Jung Kim, Soon Auck Hong, Okran Kim, Seung Joon Kim, Ji-Hyun Yang, Eun Kyo Joung, Jin-Hyoung Kang, Sook-Hee Hong
Backgrounds: EGFR-mutant non-small cell lung cancer (NSCLC) that developed acquired resistance to EGFR-tyrosine kinase (TKI) are potential candidates for programmed death 1 (PD1) inhibitor. Results: TPS≥1% for PD-L1 and low CD8 + TIL in post-TKI tumor showed a trend for a lower PFS of EGFR-TKIs (14.2 vs 9.9 months; P = 0.060) (cohort A). Only 2 of 22 specimens (9.1%) with an acquired EGFR exon 20 T790M mutation exhibited in post-TKI TPS≥50% for PD-L1. The degree in post-TKI tumor of PD-L1 expression was varied in 19 patients (40...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290998/detection-of-somatic-variants-and-egfr-mutations-in-cell-free-dna-from-non-small-cell-lung-cancer-patients-by-ultra-deep-sequencing-using-the-ion-ampliseq-cancer-hotspot-panel-and-droplet-digital-polymerase-chain-reaction
#8
Jae Sook Sung, Hyon Yong Chong, Nak-Jung Kwon, Hae Mi Kim, Jong Won Lee, Boyeon Kim, Saet Byeol Lee, Chang Won Park, Jung Yoon Choi, Won Jin Chang, Yoon Ji Choi, Sung Yong Lee, Eun Joo Kang, Kyong Hwa Park, Yeul Hong Kim
Highly sensitive genotyping assays can detect mutations in cell-free DNA (cfDNA) from cancer patients, reflecting the biology of each patient's cancer. Because circulating tumor DNA comprises a small, variable fraction of DNA circulating in the blood, sensitive parallel multiplexing tests are required to determine mutation profiles. We prospectively examined the clinical utility of ultra-deep sequencing analysis of cfDNA from 126 non-small cell lung cancer (NSCLC) patients using the Ion AmpliSeq Cancer Hotspot Panel v2 (ICP) and validated these findings with droplet digital polymerase chain reaction (ddPCR)...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290257/primary-resistance-to-osimertinib-due-to-sclc-transformation-issue-of-t790m-determination-on-liquid-re-biopsy
#9
R Minari, P Bordi, M Del Re, F Facchinetti, F Mazzoni, F Barbieri, A Camerini, C E Comin, L Gnetti, C Azzoni, R Nizzoli, B Bortesi, E Rofi, P Petreni, N Campanini, G Rossi, R Danesi, M Tiseo
OBJECTIVES: EGFR T790M mutation is the most common mechanism of resistance to first-/second-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) and could be overcome by third-generation EGFR-TKIs, such as osimertinib. Liquid biopsy, a non-invasive technique used to test the presence of the resistant mutation, may help avoiding tissue re-biopsy. However, analysing only circulating-free DNA, information about other less frequent and coexisting resistance mechanisms may remain unrevealed...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29285395/paradoxical-response-to-osimertinib-therapy-in-a-patient-with-t790m-mutated-lung-adenocarcinoma
#10
Shinichiro Okauchi, Hajime Osawa, Kunihiko Miyazaki, Mio Kawaguchi, Hiroaki Satoh
A 'paradoxical response' to cancer treatment is a term used to describe the emergence of unexpected new lesions and the progression of existing lesions, despite appropriate and effective therapy. 'Pseudo-progression' is a phenomenon in which lymphocytes activated by an immune checkpoint inhibitor accumulate in a tumor and expand its shadow, mimicking enlargement of the primary lesion or development of a new metastatic lesion. Patients receiving cancer chemotherapy may respond differently to treatment, by exhibiting a response, deterioration, or the simultaneous occurrence of both...
January 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29285266/characterization-of-the-efficacies-of-osimertinib-and-nazartinib-against-cells-expressing-clinically-relevant-epidermal-growth-factor-receptor-mutations
#11
Keita Masuzawa, Hiroyuki Yasuda, Junko Hamamoto, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Kenzo Soejima, Tomoko Betsuyaku
Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) were developed to overcome EGFR T790M-mediated resistance to first- and second-generation EGFR-TKIs. Third-generation EGFR-TKIs, such as osimertinib and nazartinib, are effective for patients with the EGFR T790M mutation. However, there are no direct comparison data to guide the selection of a third-generation EGFR-TKI for patients with different EGFR mutations. We previously established an in vitro model to estimate the therapeutic windows of EGFR-TKIs by comparing their relative efficacies against cells expressing mutant or wild type EGFRs...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285237/outcome-of-egfr-mutated-nsclc-patients-with-met-driven-resistance-to-egfr-tyrosine-kinase-inhibitors
#12
Simon Baldacci, Julien Mazieres, Pascale Tomasini, Nicolas Girard, Florian Guisier, Clarisse Audigier-Valette, Isabelle Monnet, Marie Wislez, Maurice Pérol, Pascal Dô, Eric Dansin, Charlotte Leduc, Etienne Giroux Leprieur, Denis Moro-Sibilot, David Tulasne, Zoulika Kherrouche, Julien Labreuche, Alexis B Cortot
Background: Several mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC have been described including the T790M mutation and MET amplification. Whereas T790M mutation confers prolonged survival and sensitivity to 3rd generation TKIs, data are lacking on clinical features and outcome of MET-driven resistant EGFR-mutated NSCLC patients. Methods: Patients with metastatic EGFR-mutated NSCLC displaying high MET overexpression or MET amplification, detected on a biopsy performed after progression on EGFR TKI, were identified in 15 centers...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29262502/-precise-therapy-for-lung-cancer-patients-with-rare-sensitive-mutations-of-epidermal-growth-factor-receptor
#13
Y Li, L A Chen
Precise medicine is an emerging clinical therapeutic concept based on genomic and genetic information of patients. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is an important component of precise therapy for lung cancer patients. EGFR mutations occur mainly in exon 18 to 21, in which exon 19 deletion and exon 21 L858R point mutation that are known as sensitive mutations account for nearly 45% and 40%, respectively. Except for the above two mutations and T790M point mutation, the rest are rare mutations, including Ins19, Ins20, E709, G719, S768, L861 and some compound mutations...
December 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/29250520/design-synthesis-and-evaluation-of-ribose-modified-anilinopyrimidine-derivatives-as-egfr-tyrosine-kinase-inhibitors
#14
Xiuqin Hu, Disha Wang, Yi Tong, Linjiang Tong, Xia Wang, Lili Zhu, Hua Xie, Shiliang Li, You Yang, Yufang Xu
The synthesis of a series of ribose-modified anilinopyrimidine derivatives was efficiently achieved by utilizing DBU or tBuOLi-promoted coupling of ribosyl alcohols with 2,4,5-trichloropyrimidine as key step. Preliminary biological evaluation of this type of compounds as new EGFR tyrosine kinase inhibitors for combating EGFR L858R/T790M mutant associated with drug resistance in the treatment of non-small cell lung cancer revealed that 3-N-acryloyl-5-O-anilinopyrimidine ribose derivative 1a possessed potent and specific inhibitory activity against EGFR L858R/T790M over WT EGFR...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29247830/brief-report-phase-2-study-of-the-hsp-90-inhibitor-auy922-in-previously-treated-and-molecularly-defined-patients-with-advanced-non-small-cell-lung-cancer
#15
Enriqueta Felip, Fabrice Barlesi, Benjamin Besse, Quincy Chu, Leena Gandhi, Sang-We Kim, Enric Carcereny, Lecia V Sequist, Paal Brunsvig, Christos Chouaid, Egbert F Smit, Harry J M Groen, Dong-Wan Kim, Keunchil Park, Emin Avsar, Sebastian Szpakowski, Mikhail Akimov, Edward B Garon
INTRODUCTION: In this phase 2 study, we evaluated the activity of AUY922 in pretreated stage IV NSCLC patients. METHODS: Patients with advanced NSCLC were divided into molecularly defined strata based on mutations in EGFR, ALK, KRAS, or wild-type for all three. All patients must have received > 2 prior lines of therapy, except a fifth stratum for less pretreated EGFR cohort (EGFR < 2). In EGFR mutant and ALK-rearranged strata, prior platinum therapy was not required...
December 13, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29247383/adjusted-indirect-comparison-using-propensity-score-matching-of-osimertinib-to-platinum-based-doublet-chemotherapy-in-patients-with-egfrm-t790m-nsclc-who-have-progressed-after-egfr-tki
#16
Helen Mann, Frank Andersohn, Carolyn Bodnar, Tetsuya Mitsudomi, Tony S K Mok, James Chih-Hsin Yang, Christopher Hoyle
BACKGROUND AND OBJECTIVE: An adjusted indirect comparison was conducted to assess efficacy outcomes, particularly overall survival (OS), of osimertinib versus platinum-based doublet chemotherapy in patients with epidermal growth factor receptor-mutated (EGFRm) T790M mutation-positive non-small-cell lung cancer (NSCLC) who had progressed following an EGFR tyrosine kinase inhibitor (TKI). Analysis of treatment effect from two separate trials had the potential to more accurately estimate the magnitude of OS benefit due to absence of confounding due to treatment switching from the control arm to the osimertinib arm of the ongoing randomized control trial, AURA3...
December 15, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29246024/comparison-of-cross-platform-technologies-for-egfr-t790m-testing-in-patients-with-non-small-cell-lung-cancer
#17
REVIEW
Xuefei Li, Caicun Zhou
Somatic mutations in the gene encoding epidermal growth factor receptor (EGFR) play an important role in determining targeted treatment modalities in non-small cell lung cancer (NSCLC). The EGFR T790M mutation emerges in approximately 50% of cases who acquire resistance to tyrosine kinase inhibitors. Detecting EGFR T790M mutation in tumor tissue is challenging due to heterogeneity of the tumor, low abundance of the mutation and difficulty for re-biopsy in patients with advanced disease. Alternatively, circulating tumor DNA (ctDNA) has been proposed as a non-invasive method for mutational analysis...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29245913/epidermal-growth-factor-receptor-t790m-mutation-as-a-prognostic-factor-in-egfr-mutant-non-small-cell-lung-cancer-patients-that-acquired-resistance-to-egfr-tyrosine-kinase-inhibitors
#18
Guangzhi Ma, Jing Zhang, Hai Jiang, Nannan Zhang, Liyuan Yin, Wen Li, Qinghua Zhou
Epidermal growth factor receptor (EGFR) T790M mutation accounted for over half of drug resistance cases in EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) and led to different outcomes. This study aimed to assess the prognostic role of T790M in NSCLC patients treated with EGFR-TKIs that developed drug resistance. Eligible literatures were reviewed from various databases and a meta-analysis was performed to evaluate the prognostic role of T790M mutation in EGFR-TKIs treated patients that went progression...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29242281/fda-benefit-risk-assessment-of-osimertinib-for-the-treatment-of-metastatic-non-small-cell-lung-cancer-harboring-epidermal-growth-factor-receptor-t790m-mutation
#19
Lauretta Odogwu, Luckson Mathieu, Kirsten B Goldberg, Gideon M Blumenthal, Erin Larkins, Mallorie H Fiero, Lisa Rodriguez, Karen Bijwaard, Eunice Y Lee, Reena Philip, Ingrid Fan, Martha Donoghue, Patricia Keegan, Amy McKee, Richard Pazdur
On March 30, 2017, the U.S. Food and Drug Administration (FDA) approved osimertinib for the treatment of patients with metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive, non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed following EGFR tyrosine kinase inhibitor (TKI) therapy. Approval was based on demonstration of a statistically significant difference in the primary endpoint of progression-free survival (PFS) when comparing osimertinib with chemotherapy in an international, multicenter, open-label, randomized trial (AURA3)...
December 14, 2017: Oncologist
https://www.readbyqxmd.com/read/29239135/oxymatrine-inhibits-non-small-cell-lung-cancer-via-suppression-of-egfr-signaling-pathway
#20
Wei Li, Xinfang Yu, Shiming Tan, Wenbin Liu, Li Zhou, Haidan Liu
Epidermal growth factor receptor (EGFR) plays a crucial role in human non-small cell lung cancer (NSCLC) tumorigenesis. In this study, oxymatrine was identified as an EGFR signaling pathway inhibitor in NSCLC. Oxymatrine inhibited anchorage-dependent and independent growth of NSCLC cell lines but had no cytotoxicity in normal lung cells. We found that exposure to oxymatrine not only suppressed the activity of wild-type EGFR but also inhibited the activation of exon 19 deletion and L858R/T790M mutated EGFR. Flow cytometry analysis suggested that oxymatrine-induced cell cycle G0/G1 arrest was dependent on EGFR-Akt signaling...
December 13, 2017: Cancer Medicine
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