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https://www.readbyqxmd.com/read/28620690/acquired-resistance-to-erlotinib-in-egfr-mutation-positive-lung-adenocarcinoma-among-hispanics-clicap
#1
Andrés F Cardona, Oscar Arrieta, Martín Ignacio Zapata, Leonardo Rojas, Beatriz Wills, Noemí Reguart, Niki Karachaliou, Hernán Carranza, Carlos Vargas, Jorge Otero, Pilar Archila, Claudio Martín, Luis Corrales, Mauricio Cuello, Carlos Ortiz, Luis E Pino, Rafael Rosell, Zyanya Lucia Zatarain-Barrón
BACKGROUND: Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. PATIENTS AND METHODS: EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015...
June 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28606923/detection-of-driver-and-resistance-mutations-in-leptomeningeal-metastases-of-nsclc-by-next-generation-sequencing-of-cerebrospinal-fluid-circulating-tumor-cells
#2
Ben-Yuan Jiang, Yang-Si Li, Wei-Bang Guo, Xu-Chao Zhang, Zhihong Chen, Jian Su, Wenzhao Zhong, Xue-Ning Yang, Jinji Yang, Yang W Shao, Biao Huang, Yan-Hui Liu, Qing Zhou, Hai-Yan Tu, Hua-Jun Chen, Zhen Wang, Chongrui Xu, Bin-Chao Wang, Shu-Yu Wu, Cun-Yi Gao, Xian Zhang, Yi-Long Wu
<p>Leptomeningeal metastases (LM) are more common in non-small cell lung cancer (NSCLC) with EGFR mutations. The diagnosis is difficult by traditional imaging only, and leads to poor understanding of resistance mechanisms of LM.</p> <br />Experimental Design: <p>We compared the CellSearch Assay™, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected LM. Next-Generation sequencing that included 416 cancer-associated genes was also performed on cerebrospinal fluid circulating tumor cells (CSFCTCs) of 19 patients...
June 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28599309/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#3
Shu-Yan Han, Wei Zhao, Hai-Bo Han, Hong Sun, Dong Xue, Yan-Na Jiao, Xi-Ran He, Shan-Tong Jiang, Ping-Ping Li
Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28576746/a-higher-proportion-of-the-egfr-t790m-mutation-may-contribute-to-the-better-survival-of-patients-with-exon-19-deletions-compared-with-those-with-l858r
#4
E-E Ke, Qing Zhou, Qiu-Yi Zhang, Jian Su, Zhi-Hong Chen, Xu-Chao Zhang, Chong-Rui Xu, Jin-Ji Yang, Hai-Yan Tu, Hong-Hong Yan, Yi-Chen Zhang, Fei-Yu Niu, Yi-Long Wu
INTRODUCTION: Increasing evidence has demonstrated that exon 19 deletions (Del19) and L858R mutation in EGFR have different prognostic and predictive roles in non-small-cell lung cancer (NSCLC). We aimed to investigate whether these 2 mutations produced differences in resistance mechanisms to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). METHODS: Consecutive patients with advanced EGFR-mutant NSCLC who acquired resistance to EGFR-TKIs and underwent post-progression biopsies were enrolled...
May 30, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28575795/-11-c-erlotinib-pet-cannot-detect-acquired-erlotinib-resistance-in-nsclc-tumor-xenografts-in-mice
#5
Alexander Traxl, Taraneh Beikbaghban, Thomas Wanek, Kushtrim Kryeziu, Christine Pirker, Severin Mairinger, Johann Stanek, Thomas Filip, Michael Sauberer, Claudia Kuntner, Walter Berger, Oliver Langer
INTRODUCTION: [(11)C]Erlotinib PET has shown promise to distinguish non-small cell lung cancer (NSCLC) tumors harboring the activating epidermal growth factor receptor (EGFR) mutation delE746-A750 from tumors with wild-type EGFR. To assess the suitability of [(11)C]erlotinib PET to detect the emergence of acquired erlotinib resistance in initially erlotinib-responsive tumors, we performed in vitro binding and PET experiments in mice bearing tumor xenografts using a range of different cancer cells, which were erlotinib-sensitive or exhibited clinically relevant resistance mechanisms to erlotinib...
May 25, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28572531/egfr-g796d-mutation-mediates-resistance-to-osimertinib
#6
Di Zheng, Min Hu, Yu Bai, Xuehua Zhu, Xuesong Lu, Chunyan Wu, Jiying Wang, Li Liu, Zheng Wang, Jian Ni, Zhenfan Yang, Jianfang Xu
Osimertinib is an effective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in multiple countries and regions for patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC). Despite impressive initial tumor responses, development of drug resistance ultimately limits the benefit of this compound. Mechanisms of resistance to osimertinib are just beginning to emerge, such as EGFR C797S and L718Q mutations, BRAF V600E and PIK3CA E545K mutations, as well as ERBB2 and MET amplification...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28539465/utility-of-genomic-assessment-of-blood-derived-circulating-tumor-dna-ctdna-in-patients-with-advanced-lung-adenocarcinoma
#7
Maria Schwaederle, Sandip P Patel, Hatim Husain, Megumi Ikeda, Richard Lanman, Kimberly C Banks, AmirAli Talasaz, Lyudmila Bazhenova, Razelle Kurzrock
PURPOSE: Genomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with non-small cell lung adenocarcinoma (NSCLC) were ascertained and correlated with clinical characteristics and therapeutic outcomes. EXPERIMENTAL DESIGN: Comprehensive plasma ctDNA testing was performed in 88 consecutive patients; 34 also had tissue next generation sequencing; 29, other forms of genotyping; and 25 (28.4%) had no tissue molecular tests because of inadequate tissue or biopsy contraindications...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28521430/reduced-expression-levels-of-pten-are-associated-with-decreased-sensitivity-of-hcc827-cells-to-icotinib
#8
Yang Zhai, Yanjun Zhang, Kejun Nan, Xuan Liang
The clinical resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been linked to EGFR T790M resistance mutations or MET amplifications. Additional mechanisms underlying EGFR-TKI drug resistance remain unclear. The present study demonstrated that icotinib significantly inhibited the proliferation and increased the apoptosis rate of HCC827 cells; the cellular mRNA and protein expression levels of phosphatase and tensin homolog (PTEN) were also significantly downregulated...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515244/what-when-and-how-of-biomarker-testing-in-non-small-cell-lung-cancer
#9
Gregory L Riely
Biomarker testing is recommended for all patients diagnosed with non-small cell lung cancer. At a minimum, testing should include the mutations/fusions EGFR, ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA-approved therapies are available for these alterations. Other actionable molecular findings include RET rearrangements, BRAF(V600E) mutations, and MET exon 14 alterations. If adequate testing was not performed at treatment initiation, molecular testing should be performed before administration of subsequent lines of therapy...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28469968/the-selective-c-met-inhibitor-tepotinib-can-overcome-epidermal-growth-factor-receptor-inhibitor-resistance-mediated-by-aberrant-c-met-activation-in-nsclc-models
#10
Manja Friese-Hamim, Friedhelm Bladt, Giuseppe Locatelli, Uz Stammberger, Andree Blaukat
Non-small cell lung cancer (NSCLC) sensitive to first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often acquires resistance through secondary EGFR mutations, including the T790M mutation, aberrant c-Met receptor activity, or both. We assessed the ability of the highly selective c-Met inhibitor tepotinib to overcome EGFR TKI resistance in various xenograft models of NSCLC. In models with EGFR-activating mutations and low c-Met expression (patient explant-derived LU342, cell line PC-9), EGFR TKIs caused tumors to shrink, but growth resumed upon cessation of treatment...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28469919/osimertinib-administration-via-nasogastric-tube-in-an-egfr-t790m-positive-patient-with-leptomeningeal-metastases
#11
Takayuki Takeda, Hideki Itano, Mayumi Takeuchi, Yurika Nishimi, Masahiko Saitoh, Sorou Takeda
Patients with an epidermal growth factor receptor (EGFR) mutation are usually administered EGFR-tyrosine kinase inhibitors (TKIs) as standard-of-care treatment. However, acquired resistance occurs between 9 and 13 months. The T790M-resistant mutations are the most common, and osimertinib has been found to be effective in treating EGFR-T790M-positive patients. A 73-year-old female lung cancer patient with an EGFR-sensitizing mutation was receiving fourth-line chemotherapy when she complained of anorexia, headache, and irritability...
July 2017: Respirology Case Reports
https://www.readbyqxmd.com/read/28454365/downregulation-of-egfr-in-a-metastatic-brain-lesion-of-egfr-mutated-non-small-cell-lung-cancer-using-a-tyrosine-kinase-inhibitor-a-case-report
#12
Masatoshi Takagaki, Manabu Kinoshita, Kazumi Nishino, Masakazu Nakano, Hiroko Adachi, Morio Ueno, Masanori Kitamura, Yasunori Fujimoto, Kei Tashiro, Yasuhiko Tomita, Fumio Imamura, Toshiki Yoshimine
Brain metastasis is a common complication in patients with cancer, with lung cancer being the most frequent origin of brain metastases. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have begun to serve a pivotal role in lung cancer treatment and have been reported to demonstrate anticancer activity against brain metastases by penetrating the blood-brain barrier. The present study reports, to the best of our knowledge, the first case of EGFR-mutated non-small cell lung cancer (NSCLC) brain metastasis that was surgically resected while the lesion was responding to the EGFR-TKI erlotinib...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28408243/erlotinib-and-bevacizumab-in-patients-with-advanced-non-small-cell-lung-cancer-and-activating-egfr-mutations-belief-an-international-multicentre-single-arm-phase-2-trial
#13
Rafael Rosell, Urania Dafni, Enriqueta Felip, Alessandra Curioni-Fontecedro, Oliver Gautschi, Solange Peters, Bartomeu Massutí, Ramon Palmero, Santiago Ponce Aix, Enric Carcereny, Martin Früh, Miklos Pless, Sanjay Popat, Athanasios Kotsakis, Sinead Cuffe, Paolo Bidoli, Adolfo Favaretto, Patrizia Froesch, Noemí Reguart, Javier Puente, Linda Coate, Fabrice Barlesi, Daniel Rauch, Michael Thomas, Carlos Camps, Jose Gómez-Codina, Margarita Majem, Rut Porta, Riyaz Shah, Emer Hanrahan, Roswitha Kammler, Barbara Ruepp, Manuela Rabaglio, Marie Kassapian, Niki Karachaliou, Rachel Tam, David S Shames, Miguel A Molina-Vila, Rolf A Stahel
BACKGROUND: The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation...
May 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28332047/mechanisms-of-resistance-to-target-therapies-in-non-small-cell-lung-cancer
#14
Francesco Facchinetti, Claudia Proto, Roberta Minari, Marina Garassino, Marcello Tiseo
Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28331001/quantitative-tyrosine-phosphoproteomics-of-epidermal-growth-factor-receptor-egfr-tyrosine-kinase-inhibitor-treated-lung-adenocarcinoma-cells-reveals-potential-novel-biomarkers-of-therapeutic-response
#15
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, Guldal 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 (747)LREA(750), 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...
May 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28274743/tolerable-and-effective-combination-of-full-dose-crizotinib-and-osimertinib-targeting-met-amplification-sequentially-emerging-after-t790m-positivity-in-egfr-mutant-non-small-cell-lung-cancer
#16
Emily R York, Marileila Varella-Garcia, Tami J Bang, Dara L Aisner, D Ross Camidge
No abstract text is available yet for this article.
March 6, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28271038/successful-crizotinib-monotherapy-in-egfr-mutant-lung-adenocarcinoma-with-acquired-met-amplification-after-erlotinib-therapy
#17
Katsuhiro Yoshimura, Naoki Inui, Masato Karayama, Yusuke Inoue, Noriyuki Enomoto, Tomoyuki Fujisawa, Yutaro Nakamura, Kengo Takeuchi, Haruhiko Sugimura, Takafumi Suda
MET is a driver oncogene in non-small-cell lung cancer (NSCLC), and its amplification is associated with acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. A 56-year-old Japanese male with lung adenocarcinoma harboring an EGFR exon 21 L858R mutation received erlotinib to which he responded for 12 months. After disease progression, re-biopsy analyses revealed newly developed MET amplification. Neither EGFR exon 20 T790M mutation nor MET exon 14 mutations were detected...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28245967/pulsatile-erlotinib-in-egfr-positive-non-small-cell-lung-cancer-patients-with-leptomeningeal-and-brain-metastases-review%C3%A2-of%C3%A2-the-literature
#18
REVIEW
Joan How, Janelle Mann, Andrew N Laczniak, Maria Q Baggstrom
Patients with epidermal growth factor receptor (EGFR)-positive (EGFR(+)) non-small-cell lung cancer (NSCLC) show improved response rates when treated with tyrosine kinase inhibitors (TKIs) such as erlotinib. However, standard daily dosing of erlotinib often does not reach therapeutic concentrations within the cerebrospinal fluid (CSF), resulting in progression of central nervous system (CNS) disease. Intermittent, high-dose administration of erlotinib reaches therapeutic concentrations within the CSF and is well tolerated in patients...
February 9, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28230005/current-mechanism-of-acquired-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-and-updated-therapy-strategies-in-human-nonsmall-cell-lung-cancer
#19
REVIEW
Kaixian Zhang, Qianqian Yuan
Lung cancer continues to be a major health problem and the most common cancer-related mortality worldwide with about 80%-85% patients suffering from nonsmall cell lung cancer (NSCLC). More than 80% of NSCLC cases are often diagnosed as advanced stage and harbor epidermal growth factor receptor (EGFR) activating mutation. Although great success in initial response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are found in EGFR-mutant NSCLC patients, acquired resistance usually occurs on the continuous treatment...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28219202/-precision-treatment-after-resistance-to-first-generation-egfr-tki-in-patients-with-non-small-cell-lung-cancer
#20
C Pi, Y C Zhang, C R Xu, Q Zhou
Recently, with the research progress in molecular classification, the treatment of advanced non-small cell lung cancer (NSCLC) has been established as a model of anti-tumor treatment of precision medicine. The discovery of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has transformed the treatment of NSCLC from platinum based doublet chemotherapy into era of target therapy. EGFR-TKI, such as erlotinib and gefitinib, have been recommended as standard first-line treatment of patients with EGFR mutation...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
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