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Driver mutation lung cancer

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https://www.readbyqxmd.com/read/29351916/pathways-impacted-by-genomic-alterations-in-pulmonary-carcinoid-tumors
#1
Michael K Asiedu, Charles F Thomas, Jie Dong, Sandra C Schulte Tomaszek, Prasidda Khadka, Zhifu Sun, Farhad Kosari, Jin Jen, Julian R Molina, George Vasmatzis, Rui Kuang, Marie Christine Aubry, Ping Yang, Dennis A Wigle
PURPOSE: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29346604/unique-genetic-profiles-from-cerebrospinal-fluid-cell-free-dna-in-leptomeningeal-metastases-of-egfr-mutant-non-small-cell-lung-cancer-a-new-medium-of-liquid-biopsy
#2
Y S Li, B Y Jiang, J J Yang, X C Zhang, Z Zhang, J Y Ye, W Z Zhong, H Y Tu, H J Chen, Z Wang, C R Xu, B C Wang, H J Du, S Chuai, H Han-Zhang, J Su, Q Zhou, X N Yang, W B Guo, H H Yan, Y H Liu, L X Yan, B Huang, M M Zheng, Y L Wu
Background: Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled...
January 15, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29343775/impact-of-concurrent-genomic-alterations-detected-by-comprehensive-genomic-sequencing-on-clinical-outcomes-in-east-asian-patients-with-egfr-mutated-lung-adenocarcinoma
#3
Seijiro Sato, Masayuki Nagahashi, Terumoto Koike, Hiroshi Ichikawa, Yoshifumi Shimada, Satoshi Watanabe, Toshiaki Kikuchi, Kazuki Takada, Ryota Nakanishi, Eiji Oki, Tatsuro Okamoto, Kouhei Akazawa, Stephen Lyle, Yiwei Ling, Kazuaki Takabe, Shujiro Okuda, Toshifumi Wakai, Masanori Tsuchida
Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (Nā€‰=ā€‰100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#4
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ā‰„50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29325035/amplicon-based-next-generation-sequencing-of-plasma-cell-free-dna-for-detection-of-driver-and-resistance-mutations-in-advanced-non-small-cell-lung-cancer
#5
N Guibert, Y Hu, N Feeney, Y Kuang, V Plagnol, G Jones, K Howarth, J F Beeler, C P Paweletz, G R Oxnard
Background: Genomic analysis of plasma cell-free DNA is transforming lung cancer care, however available assays are limited by cost, turnaround time, and imperfect accuracy. Here we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). Methods: Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1 and other rare genotypes) were collected while on therapy and analyzed, blinded to tumor genotype...
January 9, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29298799/targeting-her2-aberrations-in-non-small-cell-lung-cancer-with-osimertinib
#6
Shengwu Liu, Shuai Li, Josephine Hai, Xiaoen Wang, Ting Chen, Max M Quinn, Peng Gao, Yanxi Zhang, Hongbin Ji, Darren Cross, Kwok-Kin Wong
PURPOSE: HER2 (or ERBB2) aberrations, including both amplification and mutations, have been classified as oncogenic drivers that contribute to 2-6 percent of lung adenocarcinomas. HER2 amplification is also an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). However, due to limited preclinical studies and clinical trials, currently there is still no available standard of care for lung cancer patients with HER2 aberrations. To fulfill the clinical need for targeting HER2 in non-small cell lung cancer (NSCLC) patients, we performed a comprehensive pre-clinical study to evaluate the efficacy of a third-generation TKI, osimertinib (AZD9291)...
January 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29290998/detection-of-somatic-variants-and-egfr-mutations-in-cell-free-dna-from-non-small-cell-lung-cancer-patients-by-ultra-deep-sequencing-using-the-ion-ampliseq-cancer-hotspot-panel-and-droplet-digital-polymerase-chain-reaction
#7
Jae Sook Sung, Hyon Yong Chong, Nak-Jung Kwon, Hae Mi Kim, Jong Won Lee, Boyeon Kim, Saet Byeol Lee, Chang Won Park, Jung Yoon Choi, Won Jin Chang, Yoon Ji Choi, Sung Yong Lee, Eun Joo Kang, Kyong Hwa Park, Yeul Hong Kim
Highly sensitive genotyping assays can detect mutations in cell-free DNA (cfDNA) from cancer patients, reflecting the biology of each patient's cancer. Because circulating tumor DNA comprises a small, variable fraction of DNA circulating in the blood, sensitive parallel multiplexing tests are required to determine mutation profiles. We prospectively examined the clinical utility of ultra-deep sequencing analysis of cfDNA from 126 non-small cell lung cancer (NSCLC) patients using the Ion AmpliSeq Cancer Hotspot Panel v2 (ICP) and validated these findings with droplet digital polymerase chain reaction (ddPCR)...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290256/uncommon-mutations-in-epidermal-growth-factor-receptor-and-response-to-first-and-second-generation-tyrosine-kinase-inhibitors-a-case-series-and-literature-review
#8
REVIEW
Giulia Galli, Giulia Corrao, Martina Imbimbo, Claudia Proto, Diego Signorelli, Monica Ganzinelli, Nicoletta Zilembo, Milena Vitali, Filippo de Braud, Marina Chiara Garassino, Giuseppe Lo Russo
Epidermal growth factor receptor (EGFR) is the most common driver gene involved in non small cell lung cancer (NSCLC) growth, being found in approximately 10-15% of Caucasian and 40% of Asian patients. A wide variety of pathogenic mutations, deletions, insertions and duplications have been described in EGFR exons 18-21. The presence of the most common among them (e.g. exon 21 L851R and exon 19 deletions) is associated to response to first and second generation EGFR tyrosine kinase inhibitors (TKIs), which have demonstrated clear superiority over chemotherapy in terms of both progression free survival (PFS) and overall survival (OS) in all treatment lines...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29261000/successful-treatment-using-apatinib-with-or-without-docetaxel-in-heavily-pretreated-advanced-non-squamous-non-small-cell-lung-cancer-a-case-report-and-literature-review
#9
Fengying Wu, Shijia Zhang, Guanghui Gao, Jing Zhao, Shengxiang Ren, Caicun Zhou
Although targeted therapy directed toward driver mutations has produced a significant efficacy benefit for patients with non-small cell lung cancer (NSCLC), many patients do not possess mutations associated with the approved targeted drugs. Angiogenic agents play an important role in the therapeutic strategy for advanced NSCLC. Apatinib is a novel tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. A phase II clinical trial demonstrated the survival benefit of apatinib monotherapy in advanced NSCLC...
December 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29251824/dual-drive-coexistence-of-eml4-alk-and-tpm3-ros1-fusion-in-advanced-lung-adenocarcinoma
#10
You-Cai Zhu, Xing-Hui Liao, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Jian-Guo Wei, Kai-Qi Du
We report a case of concomitant EML4-ALK and TPM3-ROS1 fusion in non-small cell lung cancer (NSCLC) in a 47-year-old Chinese man and review the clinical characteristics of this type double of fusion. The patient presented with a local tumor of the left upper lobe and underwent thoracoscopy. Postoperative surgical pathologic staging revealed T1a N0 M0 stage IA. Histological examination of the tumor showed lung adenocarcinoma. Ventana ALK (D5F3) assay of the left lung tissue was ALK negative; however, immunohistochemical assay was positive for ROS1 protein...
December 18, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29230123/molecular-targets-in-non-small-cell-lung-cancer
#11
REVIEW
Ryan Griffin, Robert A Ramirez
Background: Lung cancer is the second most common cancer in the United States among men and women, and it is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancer cases. Historically, patients with metastatic NSCLC received similar cytotoxic chemotherapy regimens. Genotyping studies have revealed genetic/molecular abnormalities in lung cancer. These driver mutations render a cancer dependent on that specific mutation's biochemical pathway for its growth and survival...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29229669/kras-the-critical-driver-and-therapeutic-target-for-pancreatic-cancer
#12
Andrew M Waters, Channing J Der
RAS genes (HRAS, KRAS, and NRAS) comprise the most frequently mutated oncogene family in human cancer. With the highest RAS mutation frequencies seen with the top three causes of cancer deaths in the United States (lung, colorectal, and pancreatic cancer), the development of anti-RAS therapies is a major priority for cancer research. Despite more than three decades of intense effort, no effective RAS inhibitors have yet to reach the cancer patient. With bitter lessons learned from past failures and with new ideas and strategies, there is renewed hope that undruggable RAS may finally be conquered...
December 11, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29221323/management-of-non-small-cell-lung-cancer-with-egfr-mutation-the-role-of-radiotherapy-in-the-era-of-tyrosine-kinase-inhibitor-therapy-opportunities-and-challenges
#13
REVIEW
Bing Xia, Shirong Zhang, Shenglin Ma
In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) was greatly promoted by the discovery of oncogenic drivers and the development of targeted therapies specific for these drivers. Somatic mutations in epidermal growth factor receptor (EGFR) are the most common type in patients with NSCLC. Small-molecule tyrosine kinase inhibitor (TKI) targeting EGFR produced relatively high response rate and long duration with acceptable toxicity profile. Also, the life expectancy in patients with active EGFR mutation has been significantly prolonged than the past...
September 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29217530/the-impact-of-smoking-and-tp53-mutations-in-lung-adenocarcinoma-patients-with-targetable-mutations-the-lung-cancer-mutation-consortium-lcmc2
#14
Dara L Aisner, Lynette M Sholl, Lynne Berry, Michael Rossi, Heidi Chen, Junya Fujimoto, Andre L Moreira, Suresh Ramalingam, Liza C Villaruz, Gregory A Otterson, Eric B Haura, Katerina Politi, Bonnie S Glisson, Jeremy Cetnar, Edward Garon, Joan Schiller, Saiama Waqar, Lecia V Sequist, Julie R Brahmer, Yu Shyr, Kelly Kugler, Ignacio Ivan Wistuba, Bruce E Johnson, John D Minna, Mark G Kris, Paul A Bunn, David J Kwiatkowski
PURPOSE Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas. PATIENTS AND METHODS Sixteen U.S. institutions enrolled 1367 lung cancer patients in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and immunohistochemistry...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29215816/efficacy-of-afatinib-in-a-previously-treated-patient-with-non-small-cell-lung-cancer-harboring-her2-mutation-case-report
#15
Cheol Kyu Park, Jae Young Hur, Chang Min Choi, Tae Ok Kim, Hyun Ju Cho, Hong Joon Shin, Jung Hwan Lim, Yoo Duk Choi, Young Chul Kim, In Jae Oh
Human epidermal growth factor receptor 2 (HER2) mutation in non-small cell lung cancer (NSCLC) is an oncogenic driver that possibly becomes a druggable target to HER2-targeted therapy. The benefit of HER2-targeted therapy is much less defined especially in eastern populations. We provide evidence of clinical benefit of afatinib in a 50-year-old Asian woman with HER2-mutant NSCLC who previously failed cytotoxic chemotherapy and gefitinib treatment. Next-generation sequencing of the tumor tissue revealed a HER2 exon 20 mutation (c...
January 1, 2018: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/29213088/nsd1-inactivation-defines-an-immune-cold-dna-hypomethylated-subtype-in-squamous-cell-carcinoma
#16
Kevin Brennan, June Ho Shin, Joshua K Tay, Marcos Prunello, Andrew J Gentles, John B Sunwoo, Olivier Gevaert
Chromatin modifying enzymes are frequently mutated in cancer, resulting in widespread epigenetic deregulation. Recent reports indicate that inactivating mutations in the histone methyltransferase NSD1 define an intrinsic subtype of head and neck squamous cell carcinoma (HNSC) that features pronounced DNA hypomethylation. Here, we describe a similar hypomethylated subtype of lung squamous cell carcinoma (LUSC) that is enriched for both inactivating mutations and deletions in NSD1. The 'NSD1 subtypes' of HNSC and LUSC are highly correlated at the DNA methylation and gene expression levels, featuring ectopic expression of developmental transcription factors and genes that are also hypomethylated in Sotos syndrome, a congenital disorder caused by germline NSD1 mutations...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29211692/a-molecular-and-cytogenetic-update-on-non-small-cell-lung-carcinoma
#17
Maximilian Becker, Lori Ryan, Alexis Dowiak, Carlos A Tirado
Lung cancer is one of the leading causes of cancer-related death worldwide. Among patients with lung cancer, approximately 85% have non-small cell lung carcinoma (NSCLC). The discovery of oncogenic driver mutations in NSCLC opened new personalized treatment options. Several methods that can identify these biomarkers are used routinely in a clinical setting to stratify patients for targeted therapy. In this review, we summarize the most clinically relevant driver genes, discuss the advantages and limitations of current clinical detection methods, and highlight the benefits of personalized treatment over standard chemotherapy...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/29199686/first-line-therapy-outcomes-in-patients-with-advanced-stage-nonsmall-cell-lung-cancer-treated-at-nongovernment-tertiary-care-centrer-in-india-experience-from-a-real-world-practice
#18
S S Hingmire, M B Sambhus, D S Kelkar, S W Joshi, K S Narsinghpura
INTRODUCTION: Reports on first line or subsequent treatment and their outcomes for patients with advanced nonsmall cell lung cancer (NSCLC) in India are scarce. The present study is an attempt to understand real world practice scenario of first-line therapy and outcome in advanced stage NSCLC patients. METHODS: Observational study was conducted at a nongovernment tertiary cancer care center. Totally 83 patients with newly diagnosed advanced NSCLC who were evaluated for further treatment from 2008 onward were included in the study...
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29199685/role-of-crizotinib-in-c-mesenchymal-epidermal-transition-positive-nonsmall-cell-lung-cancer-patients
#19
U Batra, A Jain, M Sharma, R Bajaj, M Suryavanshis
The increasing cases of NSCLC and improved understanding of its molecular biology has lead to identification of its varied driver mutations. cMET amplification has an important role as resistance mechanism for EGFR TKIs. Crizotinib is a drug which shows its anti-tumoral effect in cMET positive cases. Here we present a case series of three such patients who achieved were cMET amplified and showed partial response on Crizotinib.
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29199671/indian-consensus-statement-for-treatment-of-advanced-non-small-cell-lung-cancer-first-line-maintenance-and-second-line
#20
REVIEW
(no author information available yet)
The management of advanced nonsmall cell lung cancer (NSCLC) patients is becoming complex with the identification of driver mutations and targeted therapies. The expert group of academic medical oncologists used data from published literature, practical experience to arrive at practical consensus recommendations to treat advanced NSCLC for use by the community oncologists.
January 2017: Indian Journal of Cancer
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