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https://www.readbyqxmd.com/read/29789542/rnf25-promotes-gefitinib-resistance-in-egfr-mutant-nsclc-cells-by-inducing-nf-%C3%AE%C2%BAb-mediated-erk-reactivation
#1
Jung Hee Cho, Yeon-Mi You, Young Il Yeom, Dong Chul Lee, Bo-Kyung Kim, Misun Won, Byoung Chul Cho, Minho Kang, Seulki Park, Suk-Jin Yang, Jang Seong Kim, Jung-Ae Kim, Kyung Chan Park
Non-small cell lung cancer (NSCLC) patients with EGFR mutations initially respond well to EGFR tyrosine kinase inhibitors (TKIs) but eventually exhibit acquired or innate resistance to the therapies typically due to gene mutations, such as EGFR T790M mutation or a second mutation in the downstream pathways of EGFR. Importantly, a significant portion of NSCLC patients shows TKI resistance without any known mechanisms, calling more comprehensive studies to reveal the underlying mechanisms. Here, we investigated a synthetic lethality with gefitinib using a genome-wide RNAi screen in TKI-resistant EGFR-mutant NSCLC cells, and identified RNF25 as a novel factor related to gefitinib resistance...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789021/epidermal-growth-factor-receptor-egfr-t790m-mutation-identified-in-plasma-indicates-failure-sites-and-predicts-clinical-prognosis-in-non-small-cell-lung-cancer-progression-during-first-generation-tyrosine-kinase-inhibitor-therapy-a-prospective-observational
#2
Shirong Zhang, Lucheng Zhu, Bing Xia, Enguo Chen, Qiong Zhao, Xiaochen Zhang, Xueqin Chen, Xufeng Chen, Shenglin Ma
INTRODUCTION: Plasma circulating tumor DNA (ctDNA) is an ideal approach to detecting the epidermal growth factor receptor (EGFR) T790M mutation, which is a major mechanism of resistance to first-generation EGFR-tyrosine kinase inhibitor (TKI) therapy. The present study aimed to explore the association of ctDNA-identified T790M mutation with disease failure sites and clinical prognosis in non-small cell lung cancer (NSCLC) patients. METHODS: Patients who progressed on first-generation TKIs were categorized into failure site groups of chest limited (CF), brain limited (BF) and other (OF)...
May 22, 2018: Cancer communications
https://www.readbyqxmd.com/read/29785875/egfr-tkis-in-non-small-cell-lung-cancer-focus-on-clinical-pharmacology-and-mechanisms-of-resistance
#3
Stefano Fogli, Beatrice Polini, Marzia Del Re, Iacopo Petrini, Antonio Passaro, Stefania Crucitta, Eleonora Rofi, Romano Danesi
The clinical introduction of EGFR-TKIs within the oncologic armamentarium has changed the therapeutic landscape of non-small-cell lung cancer (NSCLC) creating widespread expectations both in patients and clinicians. However, several gaps in current understanding leave open important questions regarding the use of these drugs in clinical practice. For instance, there is uncertainty in regard to which EGFR-TKI should be given first in naive patients with EGFR-driven malignancies since different generations of drugs are available with different pharmacological profiles...
May 22, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29780711/the-continued-egfr-tki-with-cytotoxic-chemotherapy-at-progression-poison-or-medicine
#4
EDITORIAL
Shin-Kyo Yoon, Chang Min Choi, Jae Cheol Lee
No abstract text is available yet for this article.
April 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29775809/transient-asymptomatic-pulmonary-opacities-during-osimertinib-treatment-and-its-clinical-implication
#5
Hansang Lee, Ho Yun Lee, Jong-Mu Sun, Se-Hoon Lee, Youjin Kim, Song Ee Park, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
INTRODUCTION: Osimertinib is an oral, potent, irreversible 3rd generation EGFR tyrosine kinase inhibitor (TKI) approved for the treatment of T790M positive non-small cell lung cancer (NSCLC) patients who failed 1st or 2nd generation EGFR TKIs. Interstitial lung disease (ILD) is a rare complication with osimertinib, occurring in 1-3%. Recently, relatively high incidence of transient asymptomatic pulmonary opacities (TAPOs) which are different from ILD has been described. However, its clinical implication has not been fully determined yet...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29770473/icotinib-enhances-lung-cancer-cell-radiosensitivity-in-vitro-and-in-vivo-by-inhibiting-mapk-erk-and-akt-activation
#6
Yonghong Fu, Sen Zhang, Dongjie Wang, Jing Wang
Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29765525/clinical-characteristics-of-non-small-cell-lung-cancer-harboring-mutations-in-exon-20-of-egfr-or-her2
#7
Masayuki Takeda, Kazuko Sakai, Hidetoshi Hayashi, Kaoru Tanaka, Junko Tanizaki, Takayuki Takahama, Koji Haratani, Kazuto Nishio, Kazuhiko Nakagawa
Unlike common epidermal growth factor receptor gene ( EGFR ) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene ( HER2 ) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exon-20 mutations of EGFR or HER2 as detected by routine application of an amplicon-based next-generation sequencing panel...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764596/-a-case-report-of-advanced-lung-adenocarcinoma-harboring-kras-mutation-treated-with-anlotinib
#8
Yudong Su, Zhaoting Meng, Xiaoyan Xu, XinYue Wang, Ran Zuo, Yunxia Hou, Kai Li, Peng Chen
In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29764589/-influence-of-different-therapies-on-egfr-mutants-by-circulating-cell-free-dna-of-lung-adenocarcinoma-and-prognosis
#9
Fei Su, Ke Zheng, Yiyun Fu, Qian Wu, Yuan Tang, Weiya Wang, Lili Jiang
BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29763936/synergistic-inhibition-of-thalidomide-and-icotinib-on-human-non-small-cell-lung-carcinomas-through-erk-and-akt-signaling
#10
Xiang Sun, Yang Xu, Yi Wang, Qian Chen, Liu Liu, Yangyi Bao
BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. However, the survival of patients with EGFR-TKI administration is limited by the inevitable development of acquired drug resistance. Recently, multi-targeted drugs combination has been shown to be a promising strategy to improve the efficacy of EGFR-TKI treatment and enable the reduction of drug resistance in NSCLC...
May 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29761660/feasibility-of-re-biopsy-and-egfr-mutation-analysis-in-patients-with-non-small-cell-lung-cancer
#11
Tae-Ok Kim, In-Jae Oh, Bo Gun Kho, Ha Young Park, Jin Sun Chang, Cheol-Kyu Park, Hong-Joon Shin, Jung-Hwan Lim, Yong-Soo Kwon, Yu-Il Kim, Sung-Chul Lim, Young-Chul Kim, Yoo-Duk Choi
BACKGROUND: In cases of EGFR-tyrosine kinase inhibitor (TKI) failure, re-biopsy may be useful to understand resistance mechanisms and guide further treatment decisions. However, performing re-biopsy is challenging because of several hurdles. We assessed the feasibility of re-biopsy in advanced non-small cell lung cancer (NSCLC) patients in real-world clinical practice. METHODS: We retrospectively reviewed the clinical and pathologic data of advanced NSCLC patients who experienced disease progression after previous treatment with EGFR-TKIs at a single tertiary hospital in Korea between January 2014 and December 2016...
May 14, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29760799/hepatotoxicity-in-advanced-lung-adenocarcinoma-a-retrospective-study-of-2108-cases
#12
Jie Qian, Xueyan Zhang, Bo Zhang, Ping Gu, Lin Wang, Baohui Han
The study aimed to identify the risk factors and frequency of hepatotoxicity in patients with advanced lung adenocarcinoma. Liver function tests were documented in 2108 patients with advanced (IIIB/IV) lung adenocarcinoma at a single institution who received first line platinum-based doublet chemotherapy. Hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Risk factors for hepatotoxicity were assessed using logistic regression analysis. Differences in hepatotoxicity between pemetrexed and non-pemetrexed regimens were evaluated after propensity score matching...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29758295/systematic-bioinformatic-approaches-reveal-novel-gene-expression-signatures-associated-with-acquired-resistance-to-egfr-targeted-therapy-in-lung-cancer
#13
Marjan Mojtabavi Naeini, Manoochehr Tavassoli, Kamran Ghaedi
OBJECTIVES: Human non-small cell lung cancer (NSCLC) that harbors activating mutations in epidermal growth factor receptor (EGFR) initially responds to treatment with EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib but eventually tumor cells acquire resistance. To date, several gene expression profiles have been reported in TKIs-resistant EGFR-mutant NSCLC. The objective of this study is to identify robust gene expression signatures, biological processes, and promising overcoming targets for TKIs-resistant EGFR-mutant NSCLC...
May 11, 2018: Gene
https://www.readbyqxmd.com/read/29754184/discovery-of-a-potent-and-mutant-selective-egfr-inhibitor-that-overcomes-t790m-mediated-resistance-in-lung-cancer
#14
Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Young Hoon Sung, Woo Sung Kim, Sung-Eun Kim, Hyung Chul Ryu, Jae Sun Kim, Lu Guangying, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
BACKGROUND: Despite remarkable activity in epidermal growth factor receptor (EGFR)-mutant lung cancer patients, the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) is limited by the emergence of acquired resistance, which is mostly caused by a secondary T790M mutation. Fortunately, newly developed, mutant-selective EGFR-TKIs against T790M have been proven as an effective therapeutic approach although only osimertinib has received the FDA approval until now. OBJECTIVE: To determine the in vitro and in vivo efficacy of a new EGFR TKI, OBX1-012 in cells with mutant EGFR...
May 12, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29751136/anti-epidermal-growth-factor-vaccine-antibodies-enhance-the-efficacy-of-tyrosine-kinase-inhibitors-and-delay-the-emergence-of-resistance-in-egfr-mutant-lung-cancer-cells
#15
Jordi Codony-Servat, Silvia García-Roman, Miguel Ángel Molina-Vila, Jordi Bertran-Alamillo, Ana Giménez-Capitán, Santiago Viteri, Andrés F Cardona, Erik d'Hondt, Niki Karachaliou, Rafael Rosell
INTRODUCTION: Mutations in EGFR correlate with impaired response to immune checkpoint inhibitors and the development of novel immunotherapeutic approaches for EGFR mutant non-small cell lung cancer (NSCLC) is of particular interest. Immunization against EGF has demonstrated efficacy in a phase III trial including unselected NSCLC patients, but little was known about the mechanisms involved in the effects of the anti-EGF antibodies generated by vaccination (anti-EGF VacAbs) or their activity in tumor cells with EGFR mutations...
May 8, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29751135/brief-report-on-the-detection-of-the-egfr-t790m-mutation-in-exhaled-breath-condensate-from-lung-cancer-patients
#16
Robert J Smyth, Sinead M Toomey, Alexander Sartori, Emer O Hanrahan, Sinead D Cuffe, Oscar S Breathnach, Ross K Morgan, Bryan T Hennessy
The EGFR-T790M somatic mutation is the most common mechanism of resistance to Tyrosine Kinase Inhibitors (TKI) in non-small cell lung cancer. Patients with advanced disease are not always amenable to repeat biopsy for further molecular analysis. Developing non-invasive methods to detect T790M in cell-free DNA (cfDNA), in the absence of tissue is being actively investigated. Unfortunately the low sensitivity of plasma for T790M detection has limited its clinical use. Exhaled breath condensate (EBC) is an easily collected sample, known to harbour cfDNA, including lung cancer mutations...
May 8, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29748209/tas6417-a-novel-epidermal-growth-factor-receptor-inhibitor-targeting-exon-20-insertion-mutations
#17
Shinichi Hasako, Miki Terasaka, Naomi Abe, Takao Uno, Hirokazu Ohsawa, Akihiro Hashimoto, Ryoto Fujita, Kenji Tanaka, Takashige Okayama, Renu Wadhwa, Kazutaka Miyadera, Yoshimi Aoyagi, Kazuhiko Yonekura, Kenichi Matsuo
Activating mutations in the epidermal growth factor receptor (EGFR) gene are important targets in cancer therapy because they are key drivers of non-small-cell lung cancer (NSCLC). Whereas almost all common EGFR mutations, such as exon 19 deletions and the L858R point mutation in exon 21, are sensitive to EGFR-tyrosine kinase inhibitor (TKI) therapies, NSCLC driven by EGFR exon 20 insertion mutations is associated with poor clinical outcomes due to dose-limiting toxicity, demonstrating the need for a novel therapy...
May 10, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29748023/cost-effectiveness-analysis-of-policy-options-on-first-line-treatments-for-advanced-non-small-cell-lung-cancer-in-thailand
#18
Chulaporn Limwattananon, Supon Limwattananon, Onanong Waleekhachonloet, Thananan Rattanachotphanit
OBJECTIVES: Tyrosine kinase inhibitors (TKIs) have shown to be better for progression-free survival than chemotherapy as the first-line treatment for advanced, non-small cell lung cancer (NSCLC), especially in patients with epidermal growth factor receptor mutation (EGFR M+). This study evaluates under the Thai health system context, cost-effectiveness of (A) the use of platinum doublets for all without EGFR testing, and (B) an EGFR test followed by TKIs or platinum doublets conditional on test results...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29738763/3d-culture-system-containing-gellan-gum-restores-oncogene-dependence-in-ros1-rearrangements-non-small-cell-lung-cancer
#19
Bo Gong, Tomoko Oh-Hara, Naoya Fujita, Ryohei Katayama
The ROS1 fusion gene has been identified in approximately 1% of non-small cell lung cancer (NSCLC) cases. Several clinical studies have highlighted ROS1 as a promising therapeutic target because crizotinib, a multi-targeted drug against ROS1, ALK, and the MET proto-oncogene, has elicited remarkable responses in ROS1-rearrangements NSCLC. However, acquired resistance mediated by ROS1 kinase domain mutations has been identified and a system to assess ROS1 inhibitors for these resistant mutations is necessary for the promotion of drug development...
May 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29737372/efficacy-and-safety-of-cytotoxic-drug-chemotherapy-after-first-line-egfr-tki-treatment-in-elderly-patients-with-non-small-cell-lung-cancer-harboring-sensitive-egfr-mutations
#20
Hisao Imai, Hiroyuki Minemura, Tomohide Sugiyama, Yutaka Yamada, Kyoichi Kaira, Kenya Kanazawa, Takashi Kasai, Takayuki Kaburagi, Koichi Minato
PURPOSE: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment is similar to that of first-line cytotoxic drug chemotherapy in elderly patients aged ≥ 75 years harboring sensitive EGFR mutations is unclear. Therefore, we aimed to investigate the efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations...
May 8, 2018: Cancer Chemotherapy and Pharmacology
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