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https://www.readbyqxmd.com/read/29334606/the-association-of-acquired-t790m-mutation-with-clinical-characteristics-after-resistance-to-first-line-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-in-lung-adenocarcinoma
#1
Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Kun-Chieh Chen, Chia-Hung Hsu, Kang-Yi Su, Jeremy J W Chen, Huei-Wen Chen, Sung-Liang Yu, Tsung-Ying Yang, Gee-Chen Chang
Purpose: The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients with acquired resistance after first-line EGFR‒tyrosine kinase inhibitor (TKI) treatment. Materials and Methods: We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status...
January 4, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29332537/azd9291-increases-sensitivity-to-radiation-in-pc-9-ir-cells-by-delaying-dna-damage-repair-after-irradiation-and-inducing-apoptosis
#2
Shenghai Wu, Lucheng Zhu, Linglan Tu, Sumei Chen, Haixiu Huang, Jingjing Zhang, Shenglin Ma, Shirong Zhang
AZD9291 is a novel, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which is administered orally. It has been proven effective in non-small cell lung cancer (NSCLC) patients, with both EGFR-sensitizing and EGFR T790M mutations in preclinical models. However, the potential therapeutic effects of AZD9291 combined with other modalities, including ionizing radiation, are not well understood. The presence of AZD9291 significantly increases the cell-killing effects of radiation in PC-9-IR cells with a secondary EGFR mutation (T790M), which was developed from NSCLC PC-9 cells (human lung adenocarcinoma cell with EGFR 19 exon 15 bp deletion) after chronic exposure to increasing doses of gefitinib, and in H1975 cells (human lung adenocarcinoma cell with EGFR exon 20 T790M mutation de novo), but not in PC-9 cells or in H460 cells (human lung adenocarcinoma cell with wild-type EGFR)...
January 13, 2018: Radiation Research
https://www.readbyqxmd.com/read/29331420/dacomitinib-antagonizes-multidrug-resistance-mdr-in-cancer-cells-by-inhibiting-the-efflux-activity-of-abcb1-and-abcg2-transporters
#3
Ying-Fang Fan, Wei Zhang, Leli Zeng, Zi-Ning Lei, Chao-Yun Cai, Pranav Gupta, Dong-Hua Yang, Qingbin Cui, Zuo-Dong Qin, Zhe-Sheng Chen, Louis D Trombetta
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Numerous mechanisms have been recognized that cause MDR, but one of the most important mechanisms is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, through which the efflux of various anticancer drugs against their concentration gradients is powered by ATP. In recent years, small molecular tyrosine kinase inhibitors (TKIs) have been developed for treatment in various human cancers overexpressing epidermal growth factor receptor (EGFR)...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29328407/estrogen-receptor-%C3%AE-1-activation-accelerates-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer
#4
Shengling Fu, Changyu Liu, Quanfu Huang, Sheng Fan, Hexiao Tang, Xiangning Fu, Bo Ai, Yongde Liao, Qian Chu
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR‑TKIs) have revolutionized the treatment of patients with advanced EGFR-mutant NSCLC. However, drug resistance eventually develops in the majority of patients despite an excellent initial response. The present study aimed to investigate the mechanism of acquired resistance to EGFR-TKIs and to explore strategies to overcome the resistance to EGFR-TKIs from a gender perspective...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327061/egfr-tki-associated-interstitial-pneumonitis-in-nivolumab-treated-patients-with-non-small-cell-lung-cancer
#5
Yasuo Oshima, Tetsuya Tanimoto, Koichiro Yuji, Arinobu Tojo
Importance: Nivolumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are now the standard-of-care therapies in non-small cell lung cancer (NSCLC). Although EGFR-TKIs are well understood and have well-defined safety profiles, our experience with immune checkpoint inhibitors is still growing, particularly regarding the use of combinations of different classes of antitumor agents, including both the concomitant and sequential use of such agents. Objective: To determine whether nivolumab increases EGFR-TKI-associated interstitial pneumonitis (IP)...
January 11, 2018: JAMA Oncology
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
#6
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/29321482/enhanced-yap-expression-leads-to-egfr-tki-resistance-in-lung-adenocarcinomas
#7
Ting-Fang Lee, Yu-Chi Tseng, Phung Anh Nguyen, Yu-Chuan Li, Chao-Chi Ho, Cheng-Wen Wu
Epidermal growth factor receptor (EGFR) mutation is prevalently expressed in lung adenocarcinoma cases and acts as one of the major driving oncogenes. EGFR tyrosine kinase inhibitors (TKIs) have been used in patients with EGFR-mutant as an effective targeted therapy in lung adenocarcinoma, but drug resistance and tumor recurrence inevitably occurs. Recently, Yes-associate protein (YAP) has been reported to promote multiple cancer cell properties, such as promoting cell proliferation, epithelial-mesenchymal transition and drug resistance...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317963/neutrophil-to-lymphocyte-ratio-predicts-overall-survival-of-advanced-non-small-cell-lung-cancer-harboring-mutant-epidermal-growth-factor-receptor
#8
Seigo Minami, Yoshitaka Ogata, Shouichi Ihara, Suguru Yamamoto, Kiyoshi Komuta
Background: Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be prognostic biomarkers in various cancers, including non-small cell lung cancer (NSCLC). However, little has been known about these two ratios for a specific population of NSCLC harboring active epidermal growth factor receptor (EGFR) mutation. Methods: We retrospectively reviewed electrical medical records of 152 patients who met the following criteria: NSCLC harboring mutant EGFR, EGFR-tyrosine kinase inhibitor (EGFR-TKI) monotherapy initiated between October 2007 and February 2017 at our hospital, stage III-IV or post-surgical recurrence...
December 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/29317428/small-cell-transformation-of-alk-rearranged-non-small-cell-adenocarcinoma-of-the-lung
#9
Agnes Balla, Kenneth J Hampel, Farrah Khan, Dara L Aisner, Nikoletta Sidiropoulos
Anaplastic lymphoma kinase (ALK) gene rearrangements are present in approximately 5% of non-small-cell lung cancers (NSCLCs). These rearrangements occur because of a chromosomal inversion within the short arm of chromosome 2, which results in the formation of the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion oncogene. While NSCLC transformation to SCLC is a rare phenomenon described in EGFR mutant cancers primarily after treatment with targeted therapy, it is exceedingly rare in ALK rearranged adenocarcinomas (Toyokawa et al...
January 9, 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29317191/randomized-double-blind-phase-ib-iii-study-of-erlotinib-with-ramucirumab-or-placebo-in-previously-untreated-egfr-mutant-metastatic-non-small-cell-lung-cancer-relay-phase-ib-results
#10
Martin Reck, Edward B Garon, Luis Paz-Ares, Santiago Ponce, Jesus Corral Jaime, Oscar Juan, Ernest Nadal, Katsuyuki Kiura, Ryan C Widau, Shuang He, Rita Dalal, Pablo Lee, Kazuhiko Nakagawa
BACKGROUND: Despite the likelihood of an initial response to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), EGFR-mutant non-small-cell lung cancer (NSCLC) patients develop disease progression. Antiangiogenic agents in combination with an EGFR TKI might provide additional benefit in patients with EGFR-mutant NSCLC. In this article we report safety, exposure, and progression-free survival (PFS) results for part A (phase Ib) of RELAY, a randomized, double-blind, phase Ib/III study investigating safety and efficacy of erlotinib (EGFR TKI) with ramucirumab (anti-vascular endothelial growth factor receptor-2 antibody) or placebo in first-line EGFR-mutant stage IV NSCLC...
November 21, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29312741/disease-free-survival-improved-by-use-of-adjuvant-egfr-tyrosine-kinase-inhibitors-in-resectable-non-small-cell-lung-cancer-an-updated-meta-analysis
#11
Yonggang Yuan, Qingyuan Huang, Chang Gu, Haiquan Chen
Background: A previous meta-analysis of our research team suggested survival advantage from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after surgery in patients with EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to follow up on the findings of the previous one and presents our latest updates through the past few years. Methods: The study advanced the previous meta-analysis and included a comprehensive range of relevant studies in PubMed...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29312548/mimicking-the-bim-bh3-domain-overcomes-resistance-to-egfr-tyrosine-kinase-inhibitors-in-egfr-mutant-non-small-cell-lung-cancer
#12
Jinjing Xia, Hao Bai, Bo Yan, Rong Li, Minhua Shao, Liwen Xiong, Baohui Han
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are widely applied to treat EGFR-mutant non-small cell lung cancer (NSCLC). BIM is a BH3 domain-containing protein encoded by BCL2L11. Some EGFR-mutant NSCLC patients showing BIM deletion polymorphism are resistant to EGFR TKIs. We retrospectively investigated BIM deletion polymorphism in NSCLC patients, its correlation with EGFR TKI (erlotinib) resistance, and the mechanism underlying the drug resistance. Among 245 EGFR-mutant NSCLC patients examined, BIM deletion polymorphism was detected in 43 (12...
December 12, 2017: Oncotarget
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
#13
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/29298799/targeting-her2-aberrations-in-non-small-cell-lung-cancer-with-osimertinib
#14
Shengwu Liu, Shuai Li, Josephine Hai, Xiaoen Wang, Ting Chen, Max M Quinn, Peng Gao, Yanxi Zhang, Hongbin Ji, Darren Cross, Kwok-Kin Wong
PURPOSE: HER2 (or ERBB2) aberrations, including both amplification and mutations, have been classified as oncogenic drivers that contribute to 2-6 percent of lung adenocarcinomas. HER2 amplification is also an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). However, due to limited preclinical studies and clinical trials, currently there is still no available standard of care for lung cancer patients with HER2 aberrations. To fulfill the clinical need for targeting HER2 in non-small cell lung cancer (NSCLC) patients, we performed a comprehensive pre-clinical study to evaluate the efficacy of a third-generation TKI, osimertinib (AZD9291)...
January 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#15
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
#16
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
#17
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/29290255/egfr-rad51-fusion-variant-in-lung-adenocarcinoma-and-response-to-erlotinib-a-case-report
#18
You-Cai Zhu, Wen-Xian Wang, Chun-Wei Xu, Zheng-Bo Song, Kai-Qi Du, Gang Chen, Tang-Feng Lv, Yong Song
The most frequent epidermal growth factor receptor (EGFR) mutations of lung cancer include exon 19 in deletion and the exon 21 L858R mutation. And EGFR-tyrosine kinase inhibitor (TKI) as the standard first line treatment show good response to classical/sensitizing EGFR mutations. With the development of detection methods, some uncommon genomic mutation events such as exon 18-25 kinase domain duplications (KDD) and EGFR rearrangements (EGFR-RAD51 or EGFR-PURB) are found. We reported a case of EGFR-RAD51 fusion in non-small-cell lung cancer(NSCLC) and the efficacy of erlotinib to this type fusion of NSCLC patients...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29290252/immune-checkpoint-inhibitors-in-epidermal-growth-factor-receptor-mutant-non-small-cell-lung-cancer-current-controversies-and-future-directions
#19
REVIEW
Ross A Soo, Sun Min Lim, Nicholas L Syn, Rebecca Teng, Richie Soong, Tony S K Mok, Byoung Chul Cho
Major advances with the development of epidermal growth factor receptor tyrosine kinase inhibitors and immune check-point inhibitors have ushered in a new era in lung cancer therapy. Whilst pre-clinical studies suggest EGFR-driven NSCLC inhibit antitumor immunity through the activation of the PD-1/PD-L1 pathway, epidemiology studies suggest EGFR mutant NSCLC are more likely to have decreased PD-L1 expression. The superiority of single agent PD-1/PD-L1 inhibitors over docetaxel in pre-treated EGFR mutant NSCLC appears to be moderated...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29290249/a-phase-i-trial-of-afatinib-and-bevacizumab-in-chemo-na%C3%A3-ve-patients-with-advanced-non-small-cell-lung-cancer-harboring-egfr-mutations-okayama-lung-cancer-study-group-trial-1404
#20
Takashi Ninomiya, Naoyuki Nogami, Toshiyuki Kozuki, Daijiro Harada, Toshio Kubo, Kadoaki Ohashi, Shoichi Kuyama, Kenichiro Kudo, Akihiro Bessho, Nobuaki Fukamatsu, Nobukazu Fujimoto, Keisuke Aoe, Takuo Shibayama, Keisuke Sugimoto, Nagio Takigawa, Katsuyuki Hotta, Katsuyuki Kiura
OBJECTIVE: In advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC), treatment with afatinib, a second-generation EGFR-tyrosine kinase inhibitor (TKI), confers a significant survival benefit over platinum-based chemotherapy. The first-generation EGFR-TKIs gefitinib and erlotinib in combination with bevacizumab have improved progression-free survival. We hypothesized that the combination of afatinib with bevacizumab would further improve efficacy, and conducted a phase I trial to test this hypothesis...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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