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https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#1
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28805673/alk-status-assessment-with-liquid-biopsies-of-lung-cancer-patients
#2
REVIEW
Paul Hofman
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28801308/egfr-mutations-compromise-hypoxia-associated-radiation-resistance-through-impaired-replication-fork-associated-dna-damage-repair
#3
Mohammad Saki, Haruhiko Makino, Prashanthi Javvadi, Nozomi Tomimatsu, Lianghao Ding, Jennifer E Clark, Elaine Gavin, Kenichi Takeda, Joel Andrews, Debabrata Saha, Michael D Story, Sandeep Burma, Chaitanya Nirodi
Epidermal growth factor receptor (EGFR) signaling has been implicated in hypoxia-associated resistance to radiation or chemotherapy. Non-small cell lung carcinomas (NSCLC) with activating L858R or ΔE746-E750 EGFR mutations exhibit elevated EGFR activity and downstream signaling. Here, relative to wild type (WT) EGFR, mutant (MT) EGFR expression significantly increases radiosensitivity in hypoxic cells. Gene expression profiling in human bronchial epithelial cells (HBEC) revealed that MT-EGFR expression elevated transcripts related to cell cycle and replication in aerobic and hypoxic conditions and down-regulated RAD50, a critical component of non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways...
August 11, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28801183/paired-phase-ii-studies-of-erlotinib-bevacizumab-for-advanced-bronchioloalveolar-carcinoma-or-never-smokers-with-advanced-non-small-cell-lung-cancer-swog-s0635-and-s0636-trials
#4
Howard L West, James Moon, Antoinette J Wozniak, Philip Mack, Fred R Hirsch, Martin J Bury, Myron Kwong, Dorothy D Nguyen, Dennis F Moore, Jieling Miao, Mary Redman, Karen Kelly, David R Gandara
BACKGROUND: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636)...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28800007/comparison-of-epidermal-growth-factor-receptor-gene-mutations-identified-using-pleural-effusion-and-primary-tumor-tissue-samples-in-non-small-cell-lung-cancer
#5
Nan Liu, Rui-Ze Sun, Jiang Du, Qian-Ze Dong, Chui-Feng Fan, Qing-Chang Li, En-Hua Wang, Yang Liu
BACKGROUND: Although the use of pleural effusion samples for epidermal growth factor receptor (EGFR) testing in lung cancer is increasing, the accuracy rate and effectiveness of identifying EGFR mutations using these samples, rather than primary tumor tissue samples, is not established. MATERIALS AND METHODS: One hundred ninety-two advanced, non-small cell lung cancer patients were enrolled into this study. All patients had primary tumor tissue and corresponding pleural effusion samples, and we employed the Amplification Refractory Mutation System to detect EGFR gene mutations in these samples...
August 9, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28798090/egfr-tyrosine-kinase-inhibitors-versus-chemotherapy-in-egfr-wild-type-pre-treated-advanced-nonsmall-cell-lung-cancer-in%C3%A2-daily-practice
#6
Pascale Tomasini, Solenn Brosseau, Julien Mazières, Jean-Philippe Merlio, Michèle Beau-Faller, Jean Mosser, Marie Wislez, L'Houcine Ouafik, Benjamin Besse, Isabelle Rouquette, Didier Debieuvre, Fabienne Escande, Virginie Westeel, Clarisse Audigier-Valette, Pascale Missy, Alexandra Langlais, Frank Morin, Denis Moro-Sibilot, Gérard Zalcman, Fabrice Barlesi
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are approved for second-line treatment of EGFR wild-type (EGFR-wt) nonsmall cell lung cancer (NSCLC). However, results from randomised trials performed to compare EGFR-TKIs with chemotherapy in this population did not show any survival benefit. In the era of immunotherapy, many drugs are approved for second-line treatment of EGFR-wt NSCLC and there is a need to reassess the role of EGFR-TKIs in this setting.The Biomarkers France study is a large nationwide cohort of NSCLC patients tested for EGFR mutations...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28797274/the-pattern-of-kras-mutations-in-metastatic-colorectal-cancer-a-retrospective-audit-from-sri-lanka
#7
Nirmala Dushyanthi Sirisena, Kemal Deen, Dayupathi Eranda Nipunika Mandawala, Pumindu Herath, Vajira Harshadeva Weerabaddana Dissanayake
OBJECTIVE: Activating mutations in the KRAS gene, found in approximately 53% of metastatic colorectal cancer (mCRC) cases, can render epidermal growth factor receptor (EGFR) inhibitors ineffective. Regional differences in these mutations have been reported. This is the first study which aims to describe the pattern of KRAS mutations in a Sri Lankan cohort of mCRC patients. RESULTS: The KRAS genotypes detected in mCRC patients which have been maintained in an anonymized database were retrospectively analyzed...
August 10, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28795387/gefitinib-plus-fuzheng-kang-ai-formula-in-patients-with-advanced-non-small-cell-lung-cancer-with-epidermal-growth-factor-receptor-mutation-a-randomized-controlled-trial
#8
Xiao-Bing Yang, Xiao-Shu Chai, Wan-Yin Wu, Shun-Qin Long, Hong Deng, Zong-Qi Pan, Wen-Feng He, Yu-Shu Zhou, Gui-Ya Liao, Shu-Jing Xiao
OBJECTIVE: To evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. METHODS: A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefifitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefifitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities...
August 9, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28794806/recent-developments-in-the-treatment-of-metastatic-colorectal-cancer
#9
REVIEW
Jonathan M Loree, Scott Kopetz
Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS/tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28794650/treating-egfr-mutation-resistance-in-non-small-cell-lung-cancer-role-of-osimertinib
#10
REVIEW
Valentina Mazza, Federico Cappuzzo
The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR-mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR-wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28794368/interstitial-lung-disease-induced-by-osimertinib-for-epidermal-growth-factor-receptor-egfr-t790m-positive-non-small-cell-lung-cancer
#11
Yoshiya Matsumoto, Tomoya Kawaguchi, Norio Yamamoto, Kenji Sawa, Naoki Yoshimoto, Tomohiro Suzumura, Tetsuya Watanabe, Shigeki Mitsuoka, Kazuhisa Asai, Tatsuo Kimura, Naruo Yoshimura, Yuko Kuwae, Kazuto Hirata
A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28794362/synchronous-duodenal-cancer-and-lung-cancer-harboring-an-epidermal-growth-factor-receptor-mutation-treated-with-erlotinib-and-oral-fluoropyrimidine
#12
Norimichi Akiyama, Masato Karayama, Moriya Iwaizumi, Yukiko Kusama, Masato Kono, Hironao Hozumi, Yuzo Suzuki, Kazuki Furuhashi, Noriyuki Enomoto, Tomoyuki Fujisawa, Yutaro Nakamura, Naoki Inui, Takafumi Suda
Chemotherapy for multiple primary cancers is challenging. We describe a case of synchronous duodenal cancer with lung cancer harboring an epidermal growth factor receptor (EGFR) mutation treated with erlotinib and S-1, an oral fluoropyrimidine agent. A 78-year-old woman with advanced EGFR-mutated lung adenocarcinoma was simultaneously diagnosed with duodenal adenocarcinoma. After the treatment with erlotinib, the lung cancer responded well, but her duodenal cancer showed no response. S-1 was added to erlotinib, and the duodenal cancer demonstrated a good response with tolerable toxicities...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28793998/the-clinical-and-mutational-spectrum-of-turkish-patients-with-cystinosis
#13
Rezan Topaloglu, Bora Gulhan, Mihriban İnözü, Nur Canpolat, Alev Yilmaz, Aytül Noyan, İsmail Dursun, İbrahim Gökçe, Metin Kaya Gürgöze, Nurver Akinci, Esra Baskin, Erkin Serdaroğlu, Beltinge Demircioğlu Kiliç, Selçuk Yüksel, Duygu Övünç Hacihamdioğlu, Emine Korkmaz, Mutlu Hayran, Fatih Ozaltin
BACKGROUND AND OBJECTIVES: Infantile nephropathic cystinosis is a severe disease that occurs due to mutations in the cystinosis gene, and it is characterized by progressive dysfunction of multiple organs; >100 cystinosis gene mutations have been identified in multiple populations. Our study aimed to identify the clinical characteristics and spectrum of cystinosis gene mutations in Turkish pediatric patients with cystinosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified the clinical characteristics and spectrum of cystinosis gene mutations in Turkish patients with cystinosis in a multicenter registry that was established for data collection...
August 9, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28792659/molecular-alterations-in-pediatric-brainstem-gliomas
#14
Mikaela Porkholm, Anna Raunio, Reetta Vainionpää, Tarja Salonen, Juha Hernesniemi, Leena Valanne, Jarno Satopää, Atte Karppinen, Minna Oinas, Olli Tynninen, Virve Pentikäinen, Sanna-Maria Kivivuori
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27-mutated diffuse midline gliomas, and whether rare long-term survivors also belong to this group...
August 9, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28791631/erbb-receptors-and-cancer
#15
Zhixiang Wang
The ErbB receptor family, also known as the EGF receptor family or type I receptor family, includes the epidermal growth factor (EGF) receptor (EGFR) or ErbB1/Her1, ErbB2/Her2, ErbB3/Her3, and ErbB4/Her4. Among all RTKs, EGFR was the first RTK identified and the first one linked to cancer. Thus, EGFR has also been the most intensively studied among all RTKs. ErbB receptors are activated after homodimerization or heterodimerization. The ErbB family is unique among the various groups of receptor tyrosine kinases (RTKs) in that ErbB3 has impaired kinase activity, while ErbB2 does not have a direct ligand...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28790845/clinical-efficacy-evaluation-of-tyrosine-kinase-inhibitors-for-non-adenocarcinoma-lung-cancer-patients-harboring-egfr-sensitizing-mutations
#16
REVIEW
Xinyu Song, Zhehai Wang
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as a standard therapy have been used in EGFR-mutated adenocarcinoma of non-small-cell lung cancer (NSCLC) patients in recent years. But in current randomized prospective clinical trials, due to few cases of non-adenocarcinoma patients having been found, the efficacy of TKIs for EGFR-mutated non-adenocarcinoma and the relationship with clinicopathological characteristics remained debatable. The results of retrospective studies showed that the frequency of EGFR mutation was significantly associated with nationality, gender, smoking history, and histology type...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28783711/mmr-deficiency-and-brca2-egfr-ntrk-mutations
#17
Prashanth Gokare, Amriti R Lulla, Wafik S El-Deiry
No abstract text is available yet for this article.
August 3, 2017: Aging
https://www.readbyqxmd.com/read/28782530/chemotherapeutics-resistance-arms-race-an-update-on-mechanisms-involved-in-resistance-limiting-egfr-inhibitors-in-lung-cancer
#18
REVIEW
Pankaj Kumar Singh, Om Silakari
Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc...
August 4, 2017: Life Sciences
https://www.readbyqxmd.com/read/28781781/responses-to-crizotinib-and-chemotherapy-in-patients-with-lung-adenocarcinoma-harboring-a-concomitant-egfr-mutation-and-alk-gene-rearrangement-a-case-report-and-review-of-the-literature
#19
Yuping Li, Shanshan Su, Guoping Cai, Quan Lin, Ying Zhou, Jinsheng Ouyang, Bicheng Chen, Junru Ye, Xiuling Wu, Chengshui Chen
Previous studies have indicated that, in lung cancers, the gene rearrangement of ALK is mutually exclusive with mutations in the epidermal growth factor receptor (EGFR) gene. However, the coexistence of EML4-ALK fusions and EGFR mutations (double positive) has been occasionally reported, with frequencies ranging from 0-8%. Currently, no consensus standard therapy exists for tumors with double positive mutations. In the present case report, the case is described of a 53-year-old woman with stage IV lung adenocarcinoma, harboring a concomitant EGFR mutation and ALK gene rearrangement, who was refractory to gefitinib administration but demonstrated a good response to crizotinib and pemetrexed chemotherapy...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28780976/prospective-clinical-integration-of-an-amplicon-based-next-generation-sequencing-method-to-select-advanced-non-small-cell-lung-cancer-patients-for-genotype-tailored-treatments
#20
Jon Zugazagoitia, Daniel Rueda, Nuria Carrizo, Ana Belen Enguita, David Gómez-Sánchez, Asunción Díaz-Serrano, Elisabeth Jiménez, Antonio Mérida, Rosa Calero, Ricardo Lujan, Eduardo De Miguel, Pablo Gámez, Vicente Díaz-Hellín, Juan Antonio Nuñez, Lara Iglesias, Irene Ferrer, Luis Paz-Ares, Santiago Ponce-Aix
INTRODUCTION: A substantial fraction of non-small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm. PATIENTS AND METHODS: After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs...
June 23, 2017: Clinical Lung Cancer
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