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https://www.readbyqxmd.com/read/28097086/liver-x-receptor-agonist-t0901317-reverses-resistance-of-a549-human-lung-cancer-cells-to-egfr-tki-treatment
#1
Haixia Cao, Shaorong Yu, Dan Chen, Changwen Jing, Zhuo Wang, Rong Ma, Siwen Liu, Jie Ni, Jifeng Feng, Jianzhong Wu
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective in lung cancer patients carrying sensitive EGFR mutations. In this study, we investigated if liver X receptor (LXR) agonist T0901317 could reverse the resistance of lung cancer cell lines A549 and H1650 to EGFR-TKI treatment. We found that T0901317 could make natural EGFR-TKI-resistant A549 human lung cancer cells sensitive to EGFR-TKI treatment and that this was dependent on LXRβ expression. However, T0901317 does not have a similar effect on another natural EGFR-TKI-resistant cell line H1650...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28093244/novel-mutations-on-egfr-leu792-potentially-correlate-to-acquired-resistance-to-osimertinib-in-advanced-nsclc
#2
Kai Chen, Fei Zhou, Wenxiang Shen, Tao Jiang, Xue Wu, Xiaoling Tong, Yang W Shao, Songbing Qin, Caicun Zhou
Osimertinib is an irreversible third generation EGFR tyrosine kinase inhibitor (TKI) and has shown outstanding performances in treating EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) patients, but acquired resistance is inevitable. EGFR C797S is the most notable resistance mechanism to this drug, but other EGFR mutations may also exist. In three lung adenocarcinoma patients resistant to osimertinib, we identified recurrent novel mutations at EGFR Leu792 codon by targeted next generation sequencing (NGS) of cell free DNA (cfDNA) from plasma or pleural effusion...
January 13, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28093061/polyphyllin-ii-restores-sensitization-of-the-resistance-of-pc-9-zd-cells-to-gefitinib-by-a-negative-regulation-of-the-pi3k-akt-mtor-signaling-pathway
#3
Ruzhen Zheng, Hao Jiang, Jinhui Li, Xinge Liu, Hongwei Xu
: EGFR tyrosine kinase inhibitors (TKIs) are widely used for advanced non-small cell lung cancer (NSCLC) patients with a sensitizing EGFR mutation and provide a promising treatment strategy. However, acquired resistance to EGFR-TKIs restrict their application. The mechanisms underlying acquired resistance to TKIs have been explored and Phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway plays a very important role in NSCLC development as well as EGFR-TKI resistance. Polyphyllin II(PP II) is the main steroidal saponin constituent which derives from the root of Paris polychylia...
December 13, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28089594/epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-sensitive-exon-19-insertion-and-exon-20-insertion-in-patients-with-advanced-non-small-cell-lung-cancer
#4
Yen-Ting Lin, Yi-Nan Liu, Shang-Gin Wu, James Chih-Hsin Yang, Jin-Yuan Shih
BACKGROUND: The clinical responsiveness to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with exon 19 insertion and the specific exon 20 insertion (A763_Y764 insFQEA) are still not well known. MATERIALS AND METHODS: We analyzed cancer specimens taken from NSCLC patients for EGFR mutations using RNA reverse transcription polymerase chain reaction or direct DNA sequencing. The clinical course and responsiveness to an EGFR TKI in patients with EGFR exon 19 insertion or exon 20 insertion (A763_Y764 insFQEA) were recorded...
December 28, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28089159/immunohistochemistry-for-egfr-mutation-detection-in-non-small-cell-lung-cancer
#5
Nina Turnšek Hitij, Izidor Kern, Aleksander Sadikov, Lea Knez, Karmen Stanič, Matjaž Zwitter, Tanja Cufer
INTRODUCTION: The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation-positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing. METHODS: The trial included 79 consecutive EGFR mutation-positive and 29 EGFR mutation-negative NSCLC cases diagnosed with reflex PCR-based testing...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#6
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28079142/the-prognostic-role-of-egfr-tkis-for-patients-with-advanced-non-small-cell-lung-cancer
#7
Dan Zhao, Xuejing Chen, Na Qin, Dan Su, Lijuan Zhou, Quan Zhang, Xi Li, Xinyong Zhang, Mulan Jin, Jinghui Wang
Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28076323/clinical-outcome-of-tyrosine-kinase-inhibitors-alone-or-combined-with-radiotherapy-for-brain-metastases-from-epidermal-growth-factor-receptor-egfr-mutant-non-small-cell-lung-cancer-nsclc
#8
Qianqian Zhu, Yanan Sun, Yingying Cui, Ke Ye, Chengliang Yang, Daoke Yang, Jie Ma, Xiao Liu, Jinming Yu, Hong Ge
This study compared treatment outcomes between TKI monotherapy and TKI administration combined with brain radiotherapy (TKI + RT) in 133 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). We also evaluated the association of different epidermal growth factor receptor (EGFR) mutation subtypes with treatment outcome. To screen for potential variables affecting cranial progression free survival (PFS) and overall survival (OS), we performed univariate and multivariate analysis based on Cox proportional-hazards models...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28073786/phase-1-study-of-twice-weekly-pulse-dose-and-daily-low-dose-erlotinib-as-initial-treatment-for-patients-with-egfr-mutant-lung-cancers
#9
H A Yu, C Sima, D Feldman, L L Liu, B Vaitheesvaran, J Cross, C M Rudin, M G Kris, W Pao, F Michor, G J Riely
BACKGROUND: Patients with EGFR-mutant lung cancers treated with EGFR tyrosine kinase inhibitors (TKIs) develop clinical resistance, most commonly with acquisition of EGFR T790M. Evolutionary modeling suggests that a schedule of twice weekly pulse and daily low-dose erlotinib may delay emergence of EGFR T790M. Pulse dose erlotinib has superior central nervous system (CNS) penetration and may result in superior CNS disease control. METHODS: We evaluated toxicity, pharmacokinetics, and efficacy of twice weekly pulse and daily low-dose erlotinib...
October 25, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28066597/the-impact-of-smoking-status-on-radiologic-tumor-progression-patterns-and-response-to-epidermal-growth-factor-receptor-egfr-tyrosine-kinase-inhibitors-in-lung-adenocarcinoma-with-activating-egfr-mutations
#10
Yoon Ki Cha, Ho Yun Lee, Myung-Ju Ahn, Keunchil Park, Jin Seok Ahn, Jong-Mu Sun, Yoon-La Choi, Kyung Soo Lee
BACKGROUND: The aim of this study was to evaluate the impact of smoking on the treatment outcome of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant lung adenocarcinoma, with consideration of other factors including radiologic tumor progression pattern according to patient smoking status. METHODS: A total of 224 patients with EGFR mutant lung adenocarcinomas that were treated with EGFR-TKIs were retrospectively reviewed...
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28061471/transformation-to-small-cell-carcinoma-as-an-acquired-resistance-mechanism-to-azd9291-a-case-report
#11
Lin Li, Hui Wang, Chao Li, Zheng Wang, Ping Zhang, Xu Yan
AZD9291, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), benefits patients with T790M mutant non-small-cell lung cancer who fail treatment with first-generation EGFR TKIs. Acquisition of resistance to AZD9291 occurs inevitable and mechanisms need to be explored. We reported an advanced lung adenocarcinoma female with EGFR exon19 deletion treated on AZD9291 after failure of erlotinib and chemotherapy. Disease progressed again after 6 months' treatment of AZD9291 with hepatic metastasis...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28061461/estimation-of-cell-free-circulating-egfr-mutation-concentration-predicts-outcomes-in-nsclc-patients-treated-with-egfr-tkis
#12
Yan-Juan Zhu, Hai-Bo Zhang, Yi-Hong Liu, Fu-Li Zhang, Ya-Zhen Zhu, Yong Li, Jian-Ping Bai, Li-Rong Liu, Yan-Chun Qu, Xin Qu, Xian Chen, Yan Li, Guang-Juan Zheng
Detection of circulating tumor DNA using droplet digital polymerase chain reaction (ddPCR) is a highly-sensitive, minimally invasive alternative to serial biopsies for assessment and management of cancer. We used ddPCR to assess the utility of measuring plasma concentrations of common epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, and T790M) in 57 non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). High baseline plasma EGFR mutation (pEGFRmut) concentrations were associated with shorter progression-free survival (8...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28057155/-level-of-soluble-programmed-death-1-ligand-1-in-peripheral-blood-of-patients-with-advanced-epidermal-growth-factor-receptor-mutated-lung-adenocarcinoma-and-its-clinical-implications
#13
L Q Zhang, Y Chen, X Pan, Y F Xing, M H Shi, Y J Chen
Objective: To analyze the expression of soluble programmed death ligand 1 (sPD-L1) in the serum of patients with advanced epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma and to explore its clinical implications. Methods: Seventy-two patients with EGFR mutated advanced lung adenocarcinoma (EGFR mutation group) were included from the Department of Respiratory Diseases in The Second Affiliated Hospital of Soochow University from May 2015 to July 2016. Thirty-one patients with advanced EGFR wild type (WT) lung adenocarcinoma [EGFR WT group, diagnosed via mini specimens from bronchoscopy or transthoracic needle aspiration biopsy (TNAB), matching in sex, age and tumor stage with EGFR mutation group] were also enrolled as controls...
December 27, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28056412/toxicity-of-concurrent-stereotactic-radiotherapy-and-targeted-therapy-or-immunotherapy-a-systematic-review
#14
REVIEW
Stephanie G C Kroeze, Corinna Fritz, Morten Hoyer, Simon S Lo, Umberto Ricardi, Arjun Sahgal, Rolf Stahel, Roger Stupp, Matthias Guckenberger
BACKGROUND AND PURPOSE: Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment. MATERIAL AND METHODS: PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK"...
December 19, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28052016/total-dna-input-is-a-crucial-determinant-of-the-sensitivity-of-plasma-cell-free-dna-egfr-mutation-detection-using-droplet-digital-pcr
#15
Yu Zhang, Yan Xu, Wei Zhong, Jing Zhao, Minjiang Chen, Li Zhang, Longyun Li, Mengzhao Wang
We evaluated the use of droplet digital PCR (ddPCR) to detect plasma cell-free DNA (cfDNA) epidermal growth factor receptor (EGFR) mutations in advanced non-small cell lung cancer (NSCLC) patients. Compared with tumor-tissue-based detection, the sensitivity of ddPCR for detecting plasma cfDNA tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutations was 61.3%, the specificity was 96.7%, and the consistency rate was 81.4% (κ=0.605, 95% confidence interval: 0.501-0.706, p <0.0001). The sensitivity declined from 82...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28040594/transcriptome-analysis-of-egfr-tyrosine-kinase-inhibitors-resistance-associated-long-noncoding-rna-in-non-small-cell-lung-cancer
#16
Pei Ma, Meiling Zhang, Fengqi Nie, Zebo Huang, Jing He, Wei Li, Liang Han
The non-small cell lung cancer (NSCLC) patients harbor mutations in the epidermal growth factor receptor (EGFR) can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib, and show improved progression-free survival. However, most of the patients who are initially responsive to EGFR TKIs with activating EGFR mutations eventually develop acquired resistance after long-term therapy, and are followed by disease progression. Recently, diverse mechanisms of acquired EGFR TKI resistance have been reported, but little is known about the role of long noncoding RNAs in EGFR TKIs resistance...
December 29, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28031837/carcinomatous-pleuritis-and-pericarditis-accompanied-by-pulmonary-tuberculosis
#17
Munechika Hara, Shin-Ichiro Iwakami, Naohisa Matsumoto, Taichi Miyawaki, Ryo Wada, Kazuhisa Takahashi
Although both lung cancer and pulmonary tuberculosis (TB) commonly occur in clinical practice, little attention has been paid to their coexistence. A 62-year-old female was admitted with acute dyspnoea secondary to cardiac tamponade. During her admission, a mass lesion harbouring air bronchograms in the right upper lobe rapidly increased in size. Surgical lung, pericardial, and pleural specimens yielded TB from a nodule in the right upper lobe and lung adenocarcinoma from the pericardium and pleura. Anti-tuberculous therapy was administered and gefitinib was subsequently started after the positive identification of epidermal growth factor receptor (EGFR) mutation (exon 19 deletion)...
November 2016: Respirology Case Reports
https://www.readbyqxmd.com/read/28029530/survival-of-asian-females-with-advanced-lung-cancer-in-the-era-of-tyrosine-kinase-inhibitor-therapy
#18
Daniel J Becker, Juan P Wisnivesky, Michael L Grossbard, Abraham Chachoua, D Ross Camidge, Benjamin P Levy
INTRODUCTION: We examined the effect of access to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy on survival for Asian female (AF) EGFR mutation-enriched patients with advanced lung adenocarcinoma. MATERIALS AND METHODS: We used the Surveillance Epidemiology and End Results database to study patients with stage IV lung adenocarcinoma diagnosed from 1998 to 2012. We compared survival (lung cancer-specific survival [LCSS] and overall survival) between AFs and non-Asian males (NAMs), an EGFR mutation-enriched and EGFR mutation-unenriched population, respectively, with a diagnosis in the pre-EGFR TKI (1998-2004) and EGFR TKI (2005-2012) eras...
October 5, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28029074/a-rational-approach-to-target-the-epidermal-growth-factor-receptor-in-glioblas
#19
Madan M Kwatra
Glioblastoma (GBM) is a deadly brain cancer, and all attempts to control it have failed so far. However, the future looks bright, as we now know the molecular landscape of GBM through the work of The Cancer Genome Atlas (TCGA) program. GBMs exhibit significant inter- and intra-tumoral heterogeneity, and to control this type of tumor, a personalized approach is required. One target, whose gene is amplified and mutated in a large number of GBMs, is the epidermal growth factor receptor (EGFR). But all attempts to target it have been unsuccessful...
December 26, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28024692/synchronous-occurrence-of-squamous-cell-carcinoma-transformation-and-egfr-exon-20-s768i-mutation-as-a-novel-mechanism-of-resistance-in-egfr-mutated-lung-adenocarcinoma
#20
Lucia Longo, Maria Cecilia Mengoli, Federica Bertolini, Stefania Bettelli, Samantha Manfredini, Giulio Rossi
The occurrence of secondary EGFR mutation T790M in exon 20 and histologic "transformation" are common mechanisms underlying resistance to EGFR first- or second-generation tyrosine kinase inhibitors (TKI). We describe here on a hitherto unreported mechanism of EGFR TKI resistance synchronously combining squamous-cell carcinoma change and occurrence of the EGFR exon 20 S768I secondary mutation in a 43 year-old woman with stage IV adenocarcinoma harbouring EGFR exon 21 L858R mutation. After 8 months of response to gefitinib, the patient experienced EGFR TKI resistance and died of leptomeningeal neoplastic dissemination...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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