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Driver mutation lung cancer

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https://www.readbyqxmd.com/read/27912833/treatment-of-locally-advanced-non-small-cell-lung-cancer
#1
REVIEW
Kit Tam, Megan Daly, Karen Kelly
Locally advanced non-small cell lung cancer is a heterogeneous disease with typically poor outcomes. Select patients may benefit from the integration of surgery, whereas patients with bulky, multistation, or contralateral (N3) mediastinal involvement are managed with definitive chemoradiation. Attempts to improve outcomes through induction, consolidation, or maintenance chemotherapy or radiation dose escalation have not demonstrated a survival benefit. Current research efforts focus on the integration of novel systemic agents that exploit tumor-specific driver mutations, augment antitumor immune response, or enhance radiation sensitivity...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912827/new-targets-in-non-small-cell-lung-cancer
#2
REVIEW
Soo J Park, Soham More, Ayesha Murtuza, Brian D Woodward, Hatim Husain
With the implementation of genomic technologies into clinical practice, we have examples of the predictive benefit of targeted therapy for oncogene-addicted cancer and identified molecular dependencies in non-small cell lung cancer. The clinical success of tyrosine kinase inhibitors against epidermal growth factor receptor and anaplastic lymphoma kinase activation has shifted treatment emphasize the separation of subsets of lung cancer and genotype-directed therapy. Advances have validated oncogenic driver genes and led to the development of targeted agents...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27910964/osimertinib-a-third-generation-tyrosine-kinase-inhibitor-targeting-non-small-cell-lung-cancer-with-egfr-t790m-mutations
#3
C E McCoach, A Jimeno
Oncogenic driver mutations in the epidermal growth factor receptor (EGFR) gene have provided a focus for effective targeted therapy. Unfortunately, all patients eventually develop resistance to frontline therapy with EGFR tyrosine kinase inhibitors (TKIs). The majority of patients develop a large subclonal population of tumor cells with a T790M mutation that renders these cells resistant to first-generation TKIs. Osimertinib is a third-generation EGFR TKI that was designed to overcome resistance from T790M mutations...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27901069/molecular-profiling-of-circulating-tumour-cells-identifies-notch1-as-a-principal-regulator-in-advanced-non-small-cell-lung-cancer
#4
Javier Mariscal, Marta Alonso-Nocelo, Laura Muinelo-Romay, Jorge Barbazan, Maria Vieito, Alicia Abalo, Antonio Gomez-Tato, Casares de Cal Maria de Los Angeles, Tomas Garcia-Caballero, Carmela Rodriguez, Elena Brozos, Francisco Baron, Rafael Lopez-Lopez, Miguel Abal
Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27873490/egf-induced-ret-inhibitor-resistance-in-ccdc6-ret-lung-cancer-cells
#5
Hyun Chang, Ji Hea Sung, Sung Ung Moon, Han Soo Kim, Jin Won Kim, Jong Seok Lee
PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes...
January 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/27867542/the-expression-of-sall4-is-significantly-associated-with-egfr-but-not-kras-or-eml4-alk-mutations-in-lung-cancer
#6
Xiangbo Jia, Rulin Qian, Binbin Zhang, Song Zhao
BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide; unfortunately, its prognosis is still very poor. Therefore, developing the target molecular is very important for lung cancer diagnosis and treatment, especially in the early stage. With this in view, spalt-like transcription factor 4 (SALL4) is considered a potential biomarker for diagnosis and prognosis in cancers, including lung cancer. METHODS: In order to better investigate the association between the expression of SALL4 and driver genes mutation, 450 histopathologically diagnosed patients with lung cancer and 11 non-cancer patients were enrolled to test the expression of SALL4 and the status of driver genes mutation...
October 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27865871/clinical-impact-of-hybrid-capture-based-next-generation-sequencing-on-changes-in-treatment-decisions-in-lung-cancer
#7
Anna Belilovski Rozenblum, Maya Ilouze, Elizabeth Dudnik, Addie Dvir, Lior Soussan-Gutman, Smadar Geva, Nir Peled
INTRODUCTION: Targeted therapy significantly prolongs survival in lung adenocarcinoma. Current diagnostic guidelines include only EGFR and ALK testing. Next-generation sequencing (NGS) reveals more actionable genomic alterations (GAs) than stan dard diagnostic methods. Data on the influence of hybrid capture-based (HC-based) NGS on treatment are limited, and we investigated its impact on treatment decisions/clinical outcomes. METHODS: This retrospective study included patients with advanced lung cancer on whom HC-based NGS was performed between 11/2011-10/2015...
November 9, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27861144/inhibition-of-oxidative-phosphorylation-suppresses-the-development-of-osimertinib-resistance-in-a-preclinical-model-of-egfr-driven-lung-adenocarcinoma
#8
Matthew J Martin, Cath Eberlein, Molly Taylor, Susan Ashton, David Robinson, Darren Cross
Metabolic plasticity is an emerging hallmark of cancer, and increased glycolysis is often observed in transformed cells. Small molecule inhibitors that target driver oncogenes can potentially inhibit the glycolytic pathway. Osimertinib (AZD9291) is a novel EGFR tyrosine kinase inhibitor (TKI) that is potent and selective for sensitising (EGFRm) and T790M resistance mutations. Clinical studies have shown osimertinib to be efficacious in patients with EGFRm/ T790M advanced NSCLC who have progressed after EGFR-TKI treatment...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27826532/kras-mutations-in-the-circulating-free-dna-cfdna-of-non-small-cell-lung-cancer-nsclc-patients
#9
REVIEW
Mónica Garzón, Sergi Villatoro, Cristina Teixidó, Clara Mayo, Alejandro Martínez, Maria de Los Llanos Gil, Santiago Viteri, Daniela Morales-Espinosa, Rafael Rosell
Circulating free DNA (cfDNA) is obtained from serum or plasma by non-invasive methods such as a simple blood draw, a technique known as "liquid biopsy". Genetic analyses of driver alterations in cfDNA have proved very effective to predict survival and treatment response of cancer patients according to tumoral cfDNA burden in blood. Non-small cell lung cancer (NSCLC) patients with higher concentration of tumoral cfDNA in blood have, on average, shorter progression-free survival (PFS) and overall survival (OS)...
October 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/27826480/aesthetic-surgery-in-patients-with-lung-cancer-a-paradigm-shift
#10
David A Hidalgo, Jan Baranski, Sammy Sinno
BACKGROUND: Lung cancer is the most common cancer worldwide and the leading cause of cancer death. With the development of targeted therapy against causative driver mutations, some patients have experienced dramatic responses that have converted their disease into a chronic, stable form. Shifting concerns away from survival and back to quality-of-life issues has led some of these patients to seek aesthetic surgery. METHODS: Three patient examples are presented to illustrate current lung cancer treatment modalities, disease responses, and subsequent experiences with aesthetic surgical procedures...
October 2016: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/27825109/her2-mutations-in-chinese-patients-with-non-small-cell-lung-cancer
#11
Zhengbo Song, Xinmin Yu, Zhiyong Shi, Jun Zhao, Yiping Zhang
BACKGROUND: ERBB2 (HER2) is a driver gene identified in non-small cell lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability and treatment of HER2-positive NSCLC in Chinese population are unclear. PATIENTS AND METHODS: Eight hundred and fifty-nine patients with pathologically confirmed NSCLC were screened for HER2 mutations using Sanger sequencing. Next-generation sequencing (NGS) was performed in positive cases. HER2 amplification was detected with FISH...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27815968/a-systematic-review-of-biomarkers-for-the-prediction-of-thromboembolism-in-lung-cancer-results-practical-issues-and-proposed-strategies-for-future-risk-prediction-models
#12
REVIEW
Marliese Alexander, Kate Burbury
INTRODUCTION: This review aimed to identify candidate biomarkers for the prediction of thromboembolism (TE) in lung cancer. MATERIALS AND METHODS: Systematic review of publications indexed in PubMed or EMBASE databases in the past 5years (01/05/2011-01/05/2016) which evaluated baseline and/or longitudinal biomarker measurements as a predictor of subsequent TE (venous and arterial) in lung cancer patients. RESULTS: Of 1105 studies identified, 18 fulfilled predefined inclusion criteria: 6 prospective and 12 retrospective...
October 26, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27793199/epidemiological-study-of-her-2-mutations-among-egfr-wild-type-lung-adenocarcinoma-patients-in-china
#13
Xuefei Li, Chao Zhao, Chunxia Su, Shengxiang Ren, Xiaoxia Chen, Caicun Zhou
BACKGROUND: Human epidermal growth factor receptor (HER)-2 is a driver gene in non-small cell lung cancer (NSCLC). The present study evaluated the mutation rate of HER-2 within the wild-type epidermal growth factor receptor (EGFR) lung adenocarcinoma population in China. METHODS: Formalin-fixed, paraffin-embedded samples from 456 patients with wild-type EGFR lung adenocarcinoma were analyzed for HER-2 mutations by amplification-refractory mutation system (ARMS), and HER-2 protein expression was evaluated by immunohistochemistry...
October 28, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27791985/detection-of-circulating-tumor-dna-in-patients-with-advanced-non-small-cell-lung-cancer
#14
Yu Yao, Jinghao Liu, Lei Li, Yuan Yuan, Kejun Nan, Xin Wu, Zhenyu Zhang, Yi Wu, Xin Li, Jiaqi Zhu, Xuehong Meng, Longgang Wei, Jun Chen, Zhi Jiang
Circulating tumor DNA (ctDNA) isolated from plasma has great potential in identification of gene mutation in non-small cell lung cancers (NSCLC), which is a non-invasive technique and can avoid the inherent shortcomings of tissue biopsy. However the ability of NGS to detect gene mutation in plasma ctDNA has not been broadly explored. To assess the diagnostic ability of ctDNA for the total mutation profile, including single nucleotide variations (SNVs), insertions and deletions (indels) and gene rearrangements, we performed a targeted DNA sequencing approach to screen NSCLC related driver gene mutations in both tissue biopsies and matched blood plasma samples from 39 advanced NSCLC patients from China...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27787282/sharpening-the-attack-on-non-small-cell-lung-cancer
#15
Allison Alexander, Brenda Quincy
Advanced non-small cell lung cancer (NSCLC) has long been a diagnosis with few treatment options and poor outcomes. However, recent discoveries about the molecular biology of NSCLC are changing the way it is treated. Driver mutations that cause uncontrolled cancer cell proliferation have been discovered in some types of NSCLC. This has led to the discovery of therapies that can target a specific driver mutation in advanced NSCLC and halt cancer progression. This article reviews standard treatment of NSCLC and explores the targetable mutations of NSCLC, available targeted treatments, treatment obstacles, and the future of targeted therapy in NSCLC...
November 2016: JAAPA: Official Journal of the American Academy of Physician Assistants
https://www.readbyqxmd.com/read/27782226/-the-evolution-of-the-treatment-of-advanced-nsclc
#16
Alessandro Morabito
The therapeutic scenario of patients with advanced non-small-cell lung cancer (NSCLC) has dramatically changed in recent years, thanks to the improvement in the knowledge of the biology of NSCLC, the discovery of targetable oncogenic drivers, and the availability of new effective drugs also for non oncogenic addicted patients, defined "wild-type" (WT). NSCLC has been the first epithelial neoplasm treated with a targeted first-line therapy in patients harbouring EGFR activating mutations or ALK rearrangements, and new targeted-based agents directed versus other molecular alterations are currently in development...
October 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27760592/-driven-gene-in-patients-with-lung-squamous-cell-carcinoma-%C3%A2-analysis-of-clinicopathologic-characteristics-and-prognosis
#17
Tongtong Zhang, Junling Li
BACKGROUND: It has been proven that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and KRAS are common driver genes in non-small cell lung cancer (NSCLC). Molecular targeted therapy increases the overall response rate and progression-free survival (PFS) of patients with EGFR-sensitive mutation or echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion. However, target and targeted drugs for lung squamous cell carcinoma to indicate clinical therapy remain to be confirmed...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/27755813/clinical-outcome-of-node-negative-oligometastatic-non-small-cell-lung-cancer
#18
Kiyohiro Sakai, Masayuki Takeda, Hidetoshi Hayashi, Kaoru Tanaka, Takeshi Okuda, Amami Kato, Yasumasa Nishimura, Tetsuya Mitsudomi, Atsuko Koyama, Kazuhiko Nakagawa
INTRODUCTION: The concept of "oligometastasis" has emerged as a basis on which to identify patients with stage IV non-small cell lung cancer (NSCLC) who might be most amenable to curative treatment. Limited data have been available regarding the survival of patients with node-negative oligometastatic NSCLC. PATIENTS AND METHODS: Consecutive patients with advanced NSCLC who attended Kindai University Hospital between January 2007 and January 2016 were recruited to this retrospective study...
September 12, 2016: Thoracic Cancer
https://www.readbyqxmd.com/read/27748834/mek-inhibitors-against-met-amplified-non-small-cell-lung-cancer
#19
Masato Chiba, Yosuke Togashi, Shuta Tomida, Hiroshi Mizuuchi, Yu Nakamura, Eri Banno, Hidetoshi Hayashi, Masato Terashima, Marco A De Velasco, Kazuko Sakai, Yoshihiko Fujita, Tetsuya Mitsudomi, Kazuto Nishio
Several receptor tyrosine kinases (RTKs) including EGFR, ALK, and MET have been identified as therapeutic targets in non-small cell lung cancer (NSCLC). Among the downstream pathways of RTKs, the MAPK pathway is particularly important for cancer cell proliferation, differentiation, and survival. In this study, the effects of MEK inhibitors (trametinib and PD0325901) in several NSCLC cell lines with driver gene alterations, especially RTK genes, were tested in vitro using an MTT assay, and a wide range of sensitivities was found...
October 17, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27732995/metastatic-lung-cancer-emerging-therapeutic-strategies
#20
Sana Saif Ur Rehman, Suresh S Ramalingam
Advanced stage nonsmall cell lung cancer had been treated mainly with platinum-based doublet chemotherapy, and other cytotoxic agents that offered significant survival advantage over best supportive care, until recently. Modest improvements were achieved with the addition of antibodies targeting the vascular endothelial growth factor, and the introduction of maintenance chemotherapy. Improvements in our knowledge of lung cancer biology have shifted the current treatment paradigm from being based on histology to one based on molecular biomarkers...
October 2016: Seminars in Respiratory and Critical Care Medicine
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