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Egfr-tki treatment for lung cancer

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https://www.readbyqxmd.com/read/28548967/detection-of-activating-and-acquired-resistant-mutation-in-plasma-from-egfr-mutated-nsclc-patients-by-peptide-nucleic-acid-pna-clamping-assisted-fluorescence-melting-curve-analysis
#1
Chang Gon Kim, Hyo Sup Shim, Min Hee Hong, Yoon Jin Cha, Su Jin Heo, Hyung Soon Park, Jee Hung Kim, Jin Gu Lee, Chang Young Lee, Byoung Chul Cho, Hye Ryun Kim
This study was designed to prospectively examine whether peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper™) is feasible for the detection of activating and acquired resistant epidermal growth factor receptor (EGFR) mutation in plasma. Patients with non-small cell lung cancer harboring activating EGFR mutations who were scheduled to undergo EGFR-tyrosine kinase inhibitors (EGFR-TKIs) were enrolled between September 2011 and March 2015. A total of 102 patients with EGFR-mutated lung cancer were enrolled, 53 had available plasma samples at disease progression, and 28 underwent serial plasma sampling during EGFR-TKI treatment...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529628/cross-platform-comparison-of-four-leading-technologies-for-detecting-egfr-mutations-in-circulating-tumor-dna-from-non-small-cell-lung-carcinoma-patient-plasma
#2
Ting Xu, Xiaozheng Kang, Xiaofang You, Liang Dai, Dequan Tian, Wanpu Yan, Yongbo Yang, Hongchao Xiong, Zhen Liang, Grace Q Zhao, Shengrong Lin, Ke-Neng Chen, Guobing Xu
Analysis of circulating tumor DNA (ctDNA) is emerging as a powerful tool for guiding targeted therapy and monitoring tumor evolution in patients with non-small cell lung cancer (NSCLC), especially when representative tissue biopsies are not available. Here, we have compared the ability of four leading technology platforms to detect epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, T790M and G719X) in ctDNA from NSCLC patients. Two amplification refractory mutation systems (cobas-ARMS and ADx-ARMS), a droplet digital polymerase chain reaction (ddPCR) and a next-generation sequencing (Firefly NGS) platform were included in the comparison...
2017: Theranostics
https://www.readbyqxmd.com/read/28527899/egfr-mutation-analysis-for-prospective-patient-selection-in-two-phase-ii-registration-studies-of-osimertinib
#3
Suzanne Jenkins, James Chih-Hsin Yang, Pasi A Jänne, Kenneth S Thress, Karen Yu, Rachel Hodge, Susie Weston, Simon Dearden, Sabina Patel, Mireille Cantarini, Frances A Shepherd
INTRODUCTION: Osimertinib is an oral, CNS active, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of EGFR T790M-positive advanced non-small cell lung cancer (NSCLC). Here we evaluate EGFR mutation frequencies in two Phase II studies of osimertinib (AURA extension and AURA2). METHODS: Patients with EGFR mutation-positive advanced NSCLC provided tumor samples following progression on their latest line of therapy for mandatory central T790M testing for study selection criteria...
May 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28522592/sensitization-of-egfr-wild-type-non-small-cell-lung-cancer-cells-to-egfr-tyrosine-kinase-inhibitor-erlotinib
#4
Judith Raimbourg, Marie-Pierre Joalland, Mathilde Cabart, Ludmilla de Plater, Fanny Bouquet, Ariel Savina, Didier Decaudin, Jaafar Bennouna, François M Vallette, Lisenn Lalier
The benefit of EGFR-TKI in non-small cell lung cancer has been demonstrated in mutant EGFR tumors as first-line treatment but the benefit in wild-type EGFR tumors is marginal as well as restricted to maintenance therapy in pretreated patients. This work aimed at questioning the effects of cisplatin initial treatment on the EGFR pathway in non-small cell lung cancer and the functional consequences in vitro and in in vivo animal models of Patient-Derived Xenografts (PDX). We establish here that cisplatin pretreatment specifically sensitizes wild-type EGFR expressing cells to erlotinib, contrary to what happens in mutant-EGFR cells and with a blocking EGFR antibody, both in vitro and in vivo The sensitization entails the activation of the kinase Src upstream of EGFR, thereafter transactivating EGFR through a ligand-independent activation...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28515374/polyphyllin-i-overcomes-emt-associated%C3%A2-resistance%C3%A2-to-erlotinib-in-lung-cancer-cells-via-il-6-stat3-pathway-inhibition
#5
Wei Lou, Yan Chen, Ke-Ying Zhu, Huizi Deng, Tianhao Wu, Jun Wang
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the most important limiting factor for treatment efficiency in EGFR-mutant non-small cell lung cancer (NSCLC). Much work has linked the epithelial-mesenchymal transition (EMT) to the emergence of drug resistance, consequently, ongoing research has been focused on exploring the therapeutic options to reverse EMT for delaying or preventing drug resistance. Polyphyllin I (PPI) is a natural compound isolated from Paris polyphylla rhizomes and displayed anti-cancer properties...
May 18, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28503070/tyrosine-kinase-inhibitor-combination-therapy-in-first-line-treatment-of-non-small-cell-lung-cancer-systematic-review-and-network-meta-analysis
#6
Sarah Batson, Stephen A Mitchell, Ricarda Windisch, Elisabetta Damonte, Veronica C Munk, Noemi Reguart
INTRODUCTION: The introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced non-small-cell lung cancer (NSCLC) with EGFR+ mutations. However, most patients develop resistance, with the result that median progression-free survival (PFS) iŝ12 months. Combining EGFR-TKIs with other agents, such as bevacizumab, is a promising approach to prolonging remission. This systematic review and network meta-analysis (NMA) were undertaken to assess available evidence regarding the benefits of first-line combination therapy involving EGFR-TKIs in patients with advanced NSCLC...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28498782/clonal-history-and-genetic-predictors-of-transformation-into-small-cell-carcinomas-from-lung-adenocarcinomas
#7
June-Koo Lee, Junehawk Lee, Sehui Kim, Soyeon Kim, Jeonghwan Youk, Seongyeol Park, Yohan An, Bhumsuk Keam, Dong-Wan Kim, Dae Seog Heo, Young Tae Kim, Jin-Soo Kim, Se Hyun Kim, Jong Seok Lee, Se-Hoon Lee, Keunchil Park, Ja-Lok Ku, Yoon Kyung Jeon, Doo Hyun Chung, Peter J Park, Joon Kim, Tae Min Kim, Young Seok Ju
Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into small-cell lung cancer (SCLC) has been described as one of the major resistant mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the molecular pathogenesis is still unclear. Methods We investigated 21 patients with advanced EGFR-mutant LADCs that were transformed into EGFR TKI-resistant SCLCs. Among them, whole genome sequencing was applied for nine tumors acquired at various time points from four patients to reconstruct their clonal evolutionary history and to detect genetic predictors for small-cell transformation...
May 12, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28494184/current-status-of-research-and-treatment-for-non-small-cell-lung-cancer-in-never-smoking-females
#8
Shin Saito, Fernando Espinoza-Mercado, Hui Liu, Naohiro Sata, Xiaojiang Cui, Harmik J Soukiasian
Lung cancer is the leading cause of cancer-related deaths worldwide with over 1 million deaths each year. The overall prognosis of lung cancer patients remains unsatisfactory, with a 5-year overall survival rate of less than 15%. Although most lung cancers are a result of smoking, approximately 25% of lung cancer cases worldwide are not attributable to tobacco use. Notably, more than half of the lung cancer cases in women occur in non-smokers. Among non-small-cell lung cancer (NSCLC) cases, cigarette-smokers have a greater association with squamous cell carcinoma than adenocarcinoma, which is more common in non-smokers...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28490925/management-of-egfr-mutated-non-small-cell-lung-cancer-practical-implications-from-a-clinical-and-pathology-perspective
#9
REVIEW
M Cabanero, R Sangha, B S Sheffield, M Sukhai, M Pakkal, S Kamel-Reid, A Karsan, D Ionescu, R A Juergens, C Butts, M S Tsao
Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy. In the present article, we focus on one molecular subtype: EGFR-mutated nsclc...
April 2017: Current Oncology
https://www.readbyqxmd.com/read/28490886/apatinib-to-combat-egfr-tki-resistance-in-an-advanced-non-small-cell-lung-cancer-patient-with-unknown-egfr-status-a-case-report
#10
Yanmei Peng, Huijuan Cui, Zhe Liu, Daiwei Liu, Fan Liu, Yazhong Song, Hua Duan, Yuqin Qiu, Qiang Li
Lung adenocarcinoma is the most common pathological pattern of lung cancer. During the past decades, a number of targeted agents have been explored to treat advanced lung adenocarcinoma. In the present clinical practice, antagonists of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF)-directed therapies are widely used. In the former category, the agent erlotinib (tyrosine kinase inhibitor) has shown obvious advantages over cytotoxic therapy. Anti-VEGF therapy bevacizumab used for lung adenocarcinoma was recommended in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as first-line therapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28490462/genome-wide-dna-methylation-analysis-reveals-gabbr2-as-a-novel-epigenetic-target-for-egfr-19-deletion-lung-adenocarcinoma-with-induction-erlotinib-treatment
#11
Xiaomin Niu, Fatao Liu, Yi Zhou, Zhen Zhou, Daizhan Zhou, Ting Wang, Ziming Li, Xiangyun Ye, Yongfeng Yu, Xiaoling Weng, Hong Zhang, Junyi Ye, Meilin Liao, Yun Liu, Zhiwei Chen, Shun Lu
Purpose: The last decade has witnessed the rapid development of personalized targeted therapies in lung cancer. It is still unclear whether epigenetic changes are involved in the response to tyrosine kinase inhibitor (TKI) treatment in epidermal growth factor receptor (EGFR) mutated lung cancer. <p>Experimental Design: Methyl-sensitive cut counting sequencing (MSCC) was applied to investigate the methylation changes in paired tissues before and after erlotinib treatment for 42 days with partial response (PR) from stage IIIa (N2) lung adenocarcinoma patients (N=2) with EGFR 19 deletion...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28485170/correlation-between-circulating-tumor-cells-egfr-expression-and-t-cell-subsets-in-advanced-non-small-cell-lung-cancer-patients-after-tyrosine-kinase-inhibitor-treatment
#12
C Tu, Y Zhu, B Jiang, W He, C Jin
Research indicates that after EGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment of non-small cell lung cancer (NSCLC), patient immune function significantly improved, and that circulating tumor cells (CTCs) measurements and peripheral blood epidermal growth factor receptor (EGFR) mutation data can guide TKIs treatment. Sixty-six advanced NSCLC patients treated with TKIs were enrolled and CTCs, EGFR expression, T cell subsets and natural killer (NK) cells in peripheral blood were measured using flow cytometry before and after treatment and assessed with respect to patient prognosis...
May 9, 2017: Neoplasma
https://www.readbyqxmd.com/read/28479857/meta-analysis-of-the-impact-of-de-novo-and-acquired-egfr-t790m-mutations-on-the-prognosis-of-patients-with-non-small-cell-lung-cancer-receiving-egfr-tkis
#13
Yang Liu, Li Sun, Zhi-Cheng Xiong, Xin Sun, Shu-Ling Zhang, Jie-Tao Ma, Cheng-Bo Han
PURPOSE: The purpose of this meta-analysis was to explore the influences of pretreatment de novo and posttreatment-acquired epidermal growth factor receptor (EGFR) T790M mutations in patients with advanced non-small cell lung cancer (NSCLC) who had received tyrosine kinase inhibitors (TKIs). METHODS: We searched PubMed, Embase, and the China National Knowledge Infrastructure database for eligible literature. Data were extracted to assess the hazard ratios (HRs) for progression-free survival (PFS), overall survival (OS), and post-progression survival (PPS) and the relative ratios (RRs) for objective response rate (ORR)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28467813/a-systematic-review-and-meta-analysis-of-individual-patient-data-on-the-impact-of-the-bim-deletion-polymorphism-on-treatment-outcomes-in-epidermal-growth-factor-receptor-mutant-lung-cancer
#14
Sheila X Soh, Fahad J Siddiqui, John C Allen, Go Woon Kim, Jae Cheol Lee, Yasushi Yatabe, Manabu Soda, Hiroyuki Mano, Ross A Soo, Tan-Min Chin, Hiromichi Ebi, Seiji Yano, Keitaro Matsuo, Xiaomin Niu, Shun Lu, Kazutoshi Isobe, Jih-Hsiang Lee, James C Yang, Mingchuan Zhao, Caicun Zhou, June-Koo Lee, Se-Hoon Lee, Ji Yun Lee, Myung-Ju Ahn, Tira J Tan, Daniel S Tan, Eng-Huat Tan, S Tiong Ong, Wan-Teck Lim
BACKGROUND: A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue. RESULTS: In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454414/analysis-of-egfr-mutation-status-in-tissue-and-plasma-for-predicting-response-to-egfr-tkis-in-advanced-non-small-cell-lung-cancer
#15
Yuyan Wang, Jianchun Duan, Hanxiao Chen, Hua Bai, Tongtong An, Jun Zhao, Zhijie Wang, Minglei Zhuo, Shuhang Wang, Jie Wang
The detection of mutations in the epidermal growth factor receptor (EGFR) gene in tumor tissues has been established as the gold standard for predicting the efficacy of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small-cell lung cancer (NSCLC). The current study aimed to investigate whether the presence of co-existing EGFR mutations in tumor tissue and in cell-free tumor DNA (ctDNA) in the plasma predicts a more favorable outcome of EGFR-TKI treatment in advanced NSCLC. A total of 287 NSCLC patients who had undergone EGFR-TKI treatment were enrolled and stratified into four subgroups: Wild-type EGFR in plasma and tissue specimens (B-/T-); mutated EGFR in plasma and tissue specimens (B+/T+); mutated EGFR in only in plasma samples (B+/T-); or mutated EGFR in only tissue specimens (B-/T+)...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28451422/erlotinib-as-second-or-third-line-treatment-in-elderly-patients-with-advanced-non-small-cell-lung-cancer-keio-lung-oncology-group-study-001-klog001
#16
Masayoshi Miyawaki, Katsuhiko Naoki, Satoshi Yoda, Sohei Nakayama, Ryosuke Satomi, Takashi Sato, Shinnosuke Ikemura, Keiko Ohgino, Kota Ishioka, Daisuke Arai, Ho Namkoong, Kengo Otsuka, Masaki Miyazaki, Tetsuo Tani, Aoi Kuroda, Makoto Nishino, Hiroyuki Yasuda, Ichiro Kawada, Hidefumi Koh, Morio Nakamura, Takeshi Terashima, Fumio Sakamaki, Koichi Sayama, Tomoko Betsuyaku, Kenzo Soejima
The aim of this study was to assess the efficacy and safety of erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), as second- or third-line treatment for elderly Japanese patients with non-small-cell lung cancer (NSCLC). The patients eligible for this phase II trial were aged ≥70 years, had stage III/IV or recurrent NSCLC, and had previously received 1 or 2 chemotherapy regimens that did not include EGFR-TKIs. The patients received erlotinib at a dose of 150 mg/day. The primary endpoint was overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity...
March 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28450659/recent-management-of-patients-with-advanced-epidermal-growth-factor-receptor-mutation-non-small-cell-lung-cancer-role-of-afatinib-and-lesson-learned-for-developing-countries
#17
Zulkifli Amin, Vito Filbert Jayalie, Wulyo Rajabto
Lung cancer is a devastating disease with a high incidence, mortality and morbidity rate, especially in developing countries. Conventional treatment with cytotoxic chemotherapy has some limitations attributed to chemoresistance and toxicity. Recent advances have shown that first generation Tyrosine Kinase Inhibitor (TKI), Gefitinib and Erlotinib, and the newest available second generation Tyrosine Kinase Inhibitor (TKI), Afatinib, have the potential to be an option in the management of patients with epidermal growth factor receptor/ EGFR mutation positive advanced/ metastatic non-small cell lung cancer...
January 2017: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/28445978/epidemiological-features-of-lung-giant-cell-carcinoma-and-therapy-for-patients-with-egfr-mutations-based-on-case-reports-and-the-surveillance-epidemiology-and-end-results-seer-database
#18
Shan-Shan Weng, Ying Cao, Xiu-Jun Tang, Li-Zhen Zhu, Yi-Nuo Tan, Cai-Xia Dong, Jia-Qi Chen, Hong Shen, Ying Yuan
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard first line treatment for advanced non-small cell lung cancer (NSCLC) with sensitive EGFR mutations. Among NSCLC, giant cell carcinoma of the lung (GCCL) is a rare pathological subtype with poor prognosis, with no confirmed evidence about its epidemiological features or therapeutic efficiency of EGFR-TKIs. We present two advanced GCCLs with sensitive EGFR mutations, also collected the cases of GCCL from our hospital and the Surveillance, Epidemiology, and End Results (SEER) program...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445002/glucose-metabolism-targeting-therapy-and-withaferin-a-are-effective-for-egfr-tki-induced-drug-tolerant-persisters
#19
Kei Kunimasa, Tatsuya Nagano, Yohei Shimono, Ryota Dokuni, Tatsunori Kiriu, Shuntaro Tokunaga, Daisuke Tamura, Masatsugu Yamamoto, Motoko Tachihara, Kazuyuki Kobayashi, Miyako Satouchi, Yoshihiro Nishimura
In pathway-targeted cancer drug therapies, the relatively rapid emergence of drug-tolerant persisters (DTPs) substantially limits the overall therapeutic benefit. However, little is known about the roles of DTPs in drug resistance. In this study, we investigated the features of EGFR-TKI induced DTPs and explored a new treatment strategy to overcome the emergence of these DTPs. We used two EGFR mutated lung adenocarcinoma cell lines, PC9 and II-18. They were treated with 2 μM gefitinib for 6, 12, or 24 days or 6 month...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28442019/-progress-of-c-met-signaling-pathway-and-tkis-in-non-small-cell-lung-cancer
#20
Xiaoqing Yu, Yanjun Xu, Yun Fan
c-MET is considered a promising oncogenic driver in non-small cell lung cancer (NSCLC) after the discovery of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). MET activation including gene mutation, amplification and protein overexpression, all of these are potential therapeutic targets and are associated with poor prognosis. Clinical evidence suggests a role for MET activation as both a primary oncogenic driver in subsets of lung cancer, and as a secondary driver of acquired resistance to EGFR-tyrosine kinase inhibitor (TKI)...
April 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
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