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https://www.readbyqxmd.com/read/28341106/the-apple-trial-feasibility-and-activity-of-azd9291-osimertinib-treatment-on-positive-plasma-t790m-in-egfr-mutant-nsclc-patients-eortc-1613
#1
Jordi Remon, Jessica Menis, Baktiar Hasan, Aleksandra Peric, Eleonora De Maio, Silvia Novello, Martin Reck, Thierry Berghmans, Bartosz Wasag, Benjamin Besse, Rafal Dziadziuszko
The AZD9291 (Osimertinib) Treatment on Positive PLasma T790M in EGFR-mutant NSCLC Patients (APPLE) trial is a randomized, open-label, multicenter, 3-arm, phase II study in advanced, epidermal growth factor receptor (EGFR)-mutant and EGFR tyrosine kinase inhibitor (TKI)-naive non-small-cell lung cancer (NSCLC) patients, to evaluate the best strategy for sequencing gefitinib and osimertinib treatment. Advanced EGFR-mutant NSCLC patients, with World Health Organization performance status 0-2 who are EGFR TKI treatment-naive and eligible to receive first-line treatment with EGFR TKI will be randomized to: In all arms, a plasmatic ctDNA T790M test will be performed by a central laboratory at the Medical University of Gdansk (Poland) but will be applied as a predictive marker for making treatment decisions only in arm B...
March 1, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28333951/prognostic-value-of-plasma-egfr-ctdna-in-nsclc-patients-treated-with-egfr-tkis
#2
Chengjuan Zhang, Bing Wei, Peng Li, Ke Yang, Zhizhong Wang, Jie Ma, Yongjun Guo
OBJECTIVE: Epidermal growth factor receptor (EGFR) specific mutations have been known to improve survival of patients with non-small-cell lung carcinoma (NSCLC). However, whether there are any changes of EGFR mutations after targeted therapy and its clinical significance is unclear. This study was to identify the status of EGFR mutations after targeted therapy and predict the prognostic significance for NSCLC patients. METHODS: A total of forty-five (45) NSCLC patients who received EGFR-TKI therapy were enrolled...
2017: PloS One
https://www.readbyqxmd.com/read/28331001/quantitative-tyrosine-phosphoproteomics-of-egfr-tyrosine-kinase-inhibitor-treated-lung-adenocarcinoma-cells-reveals-potential-novel-biomarkers-of-therapeutic-response
#3
Xu Zhang, Tapan Maity, Manoj K Kashyap, Mukesh Bansal, Abhilash Venugopalan, Sahib Singh, Shivangi Awasthi, Arivusudar Marimuthu, Harrys Kishore Charles Jacob, Natalya Belkina, Stephanie Pitts, Constance M Cultraro, Shaojian Gao, Fatos Kirkali, Romi Biswas, Raghothama Chaerkady, Andrea Califano, Akhilesh Pandey, Udayan Guha
Mutations in the Epidermal growth factor receptor (EGFR) kinase domain, such as the L858R missense mutation and deletions spanning the conserved sequence 747LREA750, are sensitive to tyrosine kinase inhibitors (TKIs). The gatekeeper site residue mutation, T790M accounts for around 60% of acquired resistance to EGFR TKIs. The first generation EGFR TKIs, erlotinib and gefitinib, and the second generation inhibitor, afatinib are FDA approved for initial treatment of EGFR mutated lung adenocarcinoma. The predominant biomarker of EGFR TKI responsiveness is the presence of EGFR TKI-sensitizing mutations...
March 22, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28325254/egfr-inhibition-in-nsclc-new-findings%C3%A2-and-opened-questions
#4
REVIEW
Francesco Passiglia, Angela Listì, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Viviana Bazan, Antonio Russo
The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients' outcomes...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323493/microparticles-containing-erlotinib-loaded-solid-lipid-nanoparticles-for-treatment-of-non-small-cell-lung-cancer
#5
Zahra Bakhtiary, Jaleh Barar, Ayuob Aghanejad, Amir Ata Saei, Elhameh Nemati, Jafar Ezzati Nazhad Dolatabadi, Yadollah Omidi
Non-small cell lung cancer (NSCLC) patients with sensitizing mutations in the exons 18-21 of the epithelial growth factor receptor (EGFR) geneshowincreased kinase activity of EGFR. Hence, tyrosine kinase inhibitors (TKIs) such as erlotinib (ETB) havecommonly been used as the second line therapeutic option in metastatic NSCLC. While the ETB is available as an oral dosage form, the local delivery of this TKI to the diseased cells of the lung may ameliorate its therapeutic impacts. In the current study, we report on the development of ETB-loaded solid lipid nanoparticle (SLN) based formulation of dry powder inhaler (ETB-SLN DPI)...
March 21, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28302223/-current-status-and-prospect-of-t790m-mutation-in-non-small-cell-lung-cancer
#6
Qin Yu, Da Jiang, Ying Li
Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) is regarded as the main accepted first-line treatment on EGFR mutation in non-small cell lung cancer (NSCLC). Although targeted therapy for the first and two generation of TKIs may lead to longer progression-free survival (PFS) and better tolerance for patients, the long-term treatment will inevitably lead to drug resistance. Among them, more than 50% of acquired resistance is associated with T790M mutation. The latest guidelines from the National Comprehensive Cancer Network (NCCN) have been proposed that the three generation of TKI (Osimertinib) can be used in first-line TKI therapy progress with detecting T790M mutations in patients...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28302219/-mucoepidermoid-carcinoma-of-the-lung-report-of-29-cases
#7
Jingjing Hou, Huijuan Wang, Guowei Zhang, Yanyang Huang, Zhiyong Ma
BACKGROUND: Pulmonary mucoepidermoid carcinoma (MEC) is an extremely rare pulmonary malignant tumor, its clinical features and conditions of prognosis is not entirely clear. The aim of this study is to discuss clinical features, diagnostic and therapeutic methods, and prognosis of pulmonary MEC. METHODS: We retrospectively studied 29 pulmonary MEC patients who diagnosed from January 2006 to December 2015 in Affiliated Hospital of Zhengzhou University. The clinical features, prognosis, diagnostic and therapeutic methods were analyzed...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28300553/neutrophil-elastase-inhibitor-sivelestat-ameliorates-gefitinib-naphthalene-induced-acute-pneumonitis-in-mice
#8
Hironori Mikumo, Toyoshi Yanagihara, Naoki Hamada, Eiji Harada, Saiko Ogata-Suetsugu, Chika Ikeda-Harada, Masako Arimura-Omori, Kunihiro Suzuki, Testuya Yokoyama, Yoichi Nakanishi
Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophils played important roles in the development of the disease. This study aimed to investigate the effects of the neutrophil elastase inhibitor sivelestat on gefitinib-induced pneumonitis in mice...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28290473/phosphoproteomics-reveals-hmga1-a-ck2-substrate-as-a-drug-resistant-target-in-non-small-cell-lung-cancer
#9
Yi-Ting Wang, Szu-Hua Pan, Chia-Feng Tsai, Ting-Chun Kuo, Yuan-Ling Hsu, Hsin-Yung Yen, Wai-Kok Choong, Hsin-Yi Wu, Yen-Chen Liao, Tse-Ming Hong, Ting-Yi Sung, Pan-Chyr Yang, Yu-Ju Chen
Although EGFR tyrosine kinase inhibitors (TKIs) have demonstrated good efficacy in non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, most patients develop intrinsic and acquired resistance. We quantitatively profiled the phosphoproteome and proteome of drug-sensitive and drug-resistant NSCLC cells under gefitinib treatment. The construction of a dose-dependent responsive kinase-substrate network of 1548 phosphoproteins and 3834 proteins revealed CK2-centric modules as the dominant core network for the potential gefitinib resistance-associated proteins...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289161/distinct-afatinib-resistance-mechanisms-identified-in-lung-adenocarcinoma-harboring-an-egfr-mutation
#10
Toshimitsu Yamaoka, Tohru Ohmori, Motoi Ohba, Satoru Arata, Yasunori Murata, Sojiro Kusumoto, Koichi Ando, Hiroo Ishida, Tsukasa Ohnishi, Yasutsuna Sasaki
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are associated with significant responses in non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations. However, acquired resistance to reversible EGFR-TKIs remains a major obstacle. In particular, while the second-generation irreversible EGFR-TKI afatinib is currently used for treating NSCLC patients, the mechanisms underlying acquired afatinib resistance remain poorly understood. Here, heterogeneous mechanisms of acquired resistance were identified following long-term exposure to increasing doses of afatinib in EGFR mutant lung adenocarcinoma PC9 cells...
March 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28287083/brigatinib-combined-with-anti-egfr-antibody-overcomes-osimertinib-resistance-in-egfr-mutated-non-small-cell-lung-cancer
#11
Ken Uchibori, Naohiko Inase, Mitsugu Araki, Mayumi Kamada, Shigeo Sato, Yasushi Okuno, Naoya Fujita, Ryohei Katayama
Osimertinib has been demonstrated to overcome the epidermal growth factor receptor (EGFR)-T790M, the most relevant acquired resistance to first-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the C797S mutation, which impairs the covalent binding between the cysteine residue at position 797 of EGFR and osimertinib, induces resistance to osimertinib. Currently, there are no effective therapeutic strategies to overcome the C797S/T790M/activating-mutation (triple-mutation)-mediated EGFR-TKI resistance...
March 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28285694/sbrt-for-oligoprogressive-oncogene-addicted-nsclc
#12
REVIEW
L Basler, S G C Kroeze, M Guckenberger
Lung cancer is one of the leading causes of cancer death in men and women and treatment outcome continues to lag behind other common cancer types. A subset of lung adenocarcinoma patients exhibit a somatic mutation in EGFR or an ALK rearrangement. In these patients, targeted TKI therapy results in higher response rates, improved PFS and reduced side effects compared with platinum-based chemotherapy. Despite initial activity of the TKIs, ultimately all patients present with disease progression after about a year on TKI therapy due to resistance development...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28285689/mutations-in-tp53-pik3ca-pten-and-other-genes-in-egfr-mutated-lung-cancers-correlation-with-clinical-outcomes
#13
Paul A VanderLaan, Deepa Rangachari, Susan M Mockus, Vanessa Spotlow, Honey V Reddi, Joan Malcolm, Mark S Huberman, Loren J Joseph, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: The degree and duration of response to epidermal growth factor receptor (EGFR) inhibitors in EGFR mutated lung cancer are heterogeneous. We hypothesized that the concurrent genomic landscape of these tumors, which is currently unknown in view of the prevailing single gene assay diagnostic paradigm in clinical practice, could play a role in clinical outcomes and/or mechanisms of resistance. METHODS: We retrospectively probed our institutional lung cancer database for tumors with EGFR kinase domain mutations that were also evaluated by more comprehensive molecular profiling, and evaluated tumor response to EGFR tyrosine kinase inhibitors (TKIs)...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28285688/plasma-epidermal-growth-factor-receptor-mutation-testing-with-a-chip-based-digital-pcr-system-in-patients-with-advanced-non-small-cell-lung-cancer
#14
Norimitsu Kasahara, Hirotsugu Kenmotsu, Masakuni Serizawa, Rina Umehara, Akira Ono, Yasushi Hisamatsu, Kazushige Wakuda, Shota Omori, Kazuhisa Nakashima, Tetsuhiko Taira, Tateaki Naito, Haruyasu Murakami, Yasuhiro Koh, Keita Mori, Masahiro Endo, Takashi Nakajima, Masanobu Yamada, Masatoshi Kusuhara, Toshiaki Takahashi
OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation testing is a companion diagnostic to determine eligibility for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). Recently, plasma-based EGFR testing by digital polymerase chain reaction (dPCR), which enables accurate quantification of target DNA, has shown promise as a minimally invasive diagnostic. Here, we aimed to evaluate the accuracy of a plasma-based EGFR mutation test developed using chip-based dPCR-based detection of 3 EGFR mutations (exon 19 deletions, L858R in exon 21, and T790M in exon 20)...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28285685/combination-treatment-with-erlotinib-and-ampelopsin-overcomes-erlotinib-resistance-in-nsclc-cells-via-the-nox2-ros-bim-pathway
#15
Seung-Woo Hong, Nam-Sook Park, Min Hye Noh, Ju A Shim, Byul-Nim Ahn, Yeong Seok Kim, Daejin Kim, Hyun-Kyung Lee, Dae Young Hur
OBJECTIVES: Erlotinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), has been shown to have a dramatic effect in non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, the presence of primary resistance or acquired resistance to EGFR-TKI is the most common reason for switching to other anti-cancer agents. Even though there are newer agents that have activity in the presence of the T790M mutation, identification of potential agents that could overcome resistance to EGFR-TKI is still needed for the treatment of NSCLC patients...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28285073/development-of-an-uplc-ms-ms-method-for-quantification-of-avitinib-ac0010-and-its-five-metabolites-in-human-cerebrospinal-fluid-application-to-a-study-of-the-blood-brain-barrier-penetration-rate-of-non-small-cell-lung-cancer-patients
#16
Weicong Wang, Xin Zheng, Hanping Wang, Lu Wang, Ji Jiang, Pei Hu
Avitinib (AC0010) is a mutant-selective epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI), designed to be a targeted therapeutic agent for non-small cell lung cancer (NSCLC) patients harboring EGFR active and T790M resistant mutations. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination of Avitinib and its five metabolites (M1, M2, M4, M7, MII-6) in human cerebrospinal fluid (CSF). The samples were purified by protein precipitation and separated on a BEH C18 column (2...
March 4, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28280362/sequential-treatment-of-tyrosine-kinase-inhibitor-and-platinum-based-doublet-chemotherapy-on-egfr-mutant-non-small-cell-lung-cancer-a-meta-analysis-of-randomized-controlled-clinical-trials
#17
Lifen Qiao, Jin Wang, Guoxian Long, Yueqiang Jiang
There is debate surrounding which treatment is superior in overall survival (OS) rates in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC); first-line tyrosine kinase inhibitor (TKI) followed by second-line platinum-based doublet chemotherapy (PCT), or the reverse sequence. Cross treatment of first- and second-line TKI and PCT makes it difficult to deduce which sequence (TKI-PCT or PCT-TKI) is better for OS. Using the keywords "lung cancer" and "EGFR" we identified clinical trials within the PubMed database which were published between January 2006 and November 2016...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28277859/impact-of-a-multivariate-serum-based-proteomic-test-on-physician-treatment-recommendations-for-advanced-non-small-cell-lung-cancer
#18
Wallace L Akerley, Alix M Arnaud, Bibas Reddy, Ray D Page
OBJECTIVE: The VeriStrat * test (VS) is intended to help guide treatment decisions for patients with advanced NSCLC without an EGFR-sensitizing mutation, classifying patients into two categories. Patients classified as VSGood have a favorable prognosis and significant clinical response to EGFR-Tyrosine Kinase Inhibitors (TKI). Patients classified as VSPoor has a less favorable prognosis and exhibit no significant response to EGFR-TKIs. The objective of this paper is to assess the real-world impact of VS test results on physicians' treatment recommendations including referrals for best-supportive-care (BSC)...
March 3, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28275600/tyrosine-kinase-inhibitors-in-the-treatment-of-choroidal-metastases-from-non-small-cell-lung-cancer-a-case-report-and-review-of-literature
#19
Akshay Gopinathan Nair, Haresh T Asnani, Vinod C Mehta, Siddharth V Mehta, Rima S Pathak, Amit H Palkar, Indumati Gopinathan
BACKGROUND: Choroidal metastases being the sole presenting feature of lung cancer is rare. Erlotinib, a tyrosine kinase inhibitor (TKI), is used in the treatment of lung adenocarcinoma where tumor cells exhibit epidermal growth factor receptor (EGFR) mutations. We report a case of metastatic non-small-cell lung cancer (NSCLC) with choroidal metastasis, which was the sole presenting feature and which responded to erlotinib. METHODS: We performed a retrospective case review...
January 2017: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/28274536/chronic-myelomonocytic-leukemia-blast-crisis-in-a-patient-with-advanced-non-small-cell-lung-cancer-treated-with-egfr-tyrosine-kinase-inhibitors
#20
Hiroaki Ogata, Isamu Okamoto, Goichi Yoshimoto, Teppei Obara, Kayo Ijichi, Eiji Iwama, Taishi Harada, Koichi Akashi, Yoichi Nakanishi
A 59-year-old woman with epidermal growth factor receptor gene (EGFR) mutation-positive advanced lung adenocarcinoma was treated with afatinib after a diagnosis of chronic myelomonocytic leukemia (CMML). Twenty-one weeks later, she developed agranulocytosis, and CMML subsequently progressed to blast crisis. After complete remission of CMML, gefitinib was initiated; however, agranulocytosis recurred. This is the first reported case of both EGFR mutation-positive advanced non-small cell lung cancer with CMML, and of CMML blast crisis...
March 2017: Respiratory Investigation
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