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Driver mutation lung cancer

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https://www.readbyqxmd.com/read/28319809/abt-737-synergizes-with-cisplatin-bypassing-aberration-of-apoptotic-pathway-in-non-small-cell-lung-cancer
#1
Eun Young Kim, Ji Ye Jung, Arum Kim, Yoon Soo Chang, Se Kyu Kim
A subset of non-small cell lung cancer (NSCLC), which does not have a druggable driver mutation, is treated with platinum-based cytotoxic chemotherapy, but it develops resistance triggered by DNA damage responses. Here, we investigated the effect of activation of STAT3 by cisplatin on anti-apoptotic proteins and the effectiveness of a co-treatment with cisplatin and a BH3 mimetic, ABT-737. We analyzed the relationship between cisplatin and STAT3 pathway and effect of ABT-737, when combined with cisplatin in NSCLC cells and K-ras mutant mouse models...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28302568/mutational-profile-from-targeted-ngs-predicts-survival-in-ldct-screening-detected-lung-cancers
#2
Carla Verri, Cristina Borzi, Todd Holscher, Matteo Dugo, Andrea Devecchi, Katherine Drake, Stefano Sestini, Paola Suatoni, Elisa Romeo, Gabriella Sozzi, Ugo Pastorino, Mattia Boeri
BACKGROUND: The issue of overdiagnosis in low-dose computed tomography (LDCT)-screening trials could be addressed by the development of complementary biomarkers able to improve detection of aggressive disease. The mutation profile of LDCT screening-detected lung tumours is currently unknown. METHODS: Targeted next-generation sequencing was performed in 94 LDCT screening-detected lung tumours. Associations with clinicopathologic features, survival and the risk profile of a plasma microRNA signature classifier (MSC) were analyzed...
March 13, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28287730/discovery-of-n-3r-4r-4-fluoro-1-6-3-methoxy-1-methyl-1h-pyrazol-4-yl-amino-9-methyl-9h-purin-2-yl-pyrrolidine-3-yl-acrylamide-pf-06747775-through-structure-based-drug-design-a-high-affinity-irreversible-inhibitor-targeting-oncogenic-egfr-mutants-with-selectivity
#3
Simon Planken, Douglas Carl Behenna, Sajiv K Nair, Theodore Otto Johnson, Asako Nagata, Chau Almaden, Simon Bailey, T Eric Ballard, Louise Bernier, Hengmiao Cheng, Sujin Cho-Schultz, Deepak Dalvie, Judith G Deal, Dac M Dinh, Martin P Edwards, Rose Ann Ferre, Ketan S Gajiwala, Michelle D Hemkens, Robert S Kania, John C Kath, Jean Matthews, Brion W Murray, Sherry Niessen, Suvi T M Orr, Mason Pairish, Neal W Sach, Hong Shen, Manli Shi, James Solowiej, Khanh Tran, Elaine Tseng, Paolo Vicini, Yuli Wang, Scott L Weinrich, Ru Zhou, Michael Zientek, Longqing Liu, Yiqin Luo, Shuibo Xin, Chengyi Zhang, Jennifer Anne Lafontaine
Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR-mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGFR mutations account for approximately 50% of relapses, the most common being the gatekeeper T790M substitution that renders existing therapies ineffective. The discovery of PF-06459988 (1), an irreversible pyrrolopyrimidine inhibitor of EGFR T790M mutants was recently disclosed1...
March 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28280984/treatment-of-lung-adenocarcinoma-by-molecular-targeted-therapy-and-immunotherapy
#4
REVIEW
Motonobu Saito, Hiroyuki Suzuki, Koji Kono, Seiichi Takenoshita, Takashi Kohno
Lung adenocarcinoma (LADC) is a cancer treatable using targeted therapies against driver gene aberrations. EGFR mutations and ALK fusions are frequent gene aberrations in LADC, and personalized therapies against those aberrations have become a standard therapy. These targeted therapies have shown significant positive efficacy and tolerable toxicity compared to conventional chemotherapy, so it is necessary to identify additional druggable genetic aberrations. Other than EGFR mutations and ALK fusions, mutations in KRAS, HER2, and BRAF, and driver fusions involving RET and ROS1, have also been identified in LADC...
March 9, 2017: Surgery Today
https://www.readbyqxmd.com/read/28279655/nontypeable-haemophilus-influenzae-promoted-proliferation-of-kras-induced-early-adenomatous-lesions-is-completely-dependent-on-toll-like-receptor-signaling
#5
Christopher Jungnickel, Philipp A Schnabel, Rainer Bohle, Rainer Wiewrodt, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic obstructive pulmonary disease is a risk factor for lung cancer. COPD is characterized by chronic airway inflammation and lung infections. The airways of patients with COPD are frequently colonized with bacteria [eg, nontypeable Haemophilus influenzae (NTHi)] that cause pulmonary inflammation and exacerbations. Pulmonary adenocarcinomas are frequently associated with an activating mutation in the KRAS gene. We determined the function of Toll-like receptor (TLR) signaling on the progression of KRas-induced early adenomatous lesions in the lung...
March 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28276856/safety-of-alectinib-for-the-treatment-of-metastatic-alk-rearranged-non-small-cell-lung-cancer
#6
Viola Zhu, S H Ou
Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) may derive significant clinical benefit from targeted therapies against this driver mutation, but progression is virtually inevitable. Alectinib is a next-generation ALK inhibitor that provides a novel treatment option for this group of patients. Areas covered: In this review, we summarize the overall safety and tolerability of alectinib. Specifically, we cover cardiovascular, gastrointestinal, hepatic, musculoskeletal, and respiratory adverse events...
March 3, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28271038/successful-crizotinib-monotherapy-in-egfr-mutant-lung-adenocarcinoma-with-acquired-met-amplification-after-erlotinib-therapy
#7
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/28251125/the-first-liquid-biopsy-test-approved-is-it-a-new-era-of-mutation-testing-for-non-small-cell-lung-cancer
#8
Dorota Kwapisz
Specific mutations in epidermal growth factor receptor (EGFR) gene are predictive for response to the EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer patients (NSCLC). According to international guidelines, the molecular testing in patients with advanced NSCLC of a non-squamous subtype is recommended. However, obtain a tissue sample could be challenging. Liquid biopsy allows to determine patients suitable for EGFR-targeted therapy by analysis of circulating-free tumor DNA (cfDNA) in peripheral blood samples and might replace tissue biopsy...
February 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28250852/pet-imaging-based-phenotyping-as-a-predictive-biomarker-of-response-to-tyrosine-kinase-inhibitor-therapy-in-non-small-cell-lung-cancer-are-we-there-yet
#9
Victor H Gerbaudo, Chun K Kim
The increased understanding of the molecular pathology of different malignancies, especially lung cancer, has directed investigational efforts to center on the identification of different molecular targets and on the development of targeted therapies against these targets. A good representative is the epidermal growth factor receptor (EGFR); a major driver of non-small cell lung cancer tumorigenesis. Today, tumor growth inhibition is possible after treating lung tumors expressing somatic mutations of the EGFR gene with tyrosine kinase inhibitors (TKI)...
March 2017: Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28230015/screening-of-gene-mutations-associated-with-bone-metastasis-in-nonsmall-cell-lung-cancer
#10
Kun Zhang, Min Zhang, Jinlong Zhu, Wang Hong
OBJECTIVE: The objective of this study is to assess the gene mutation of advanced nonsmall cell lung cancer (NSCLC) patients with bone metastasis using next-generation sequencing (NGS), and screen for the driver genes which are associated with bone metastasis of lung cancer. MATERIALS AND METHODS: Eight clinicopathologic samples from advanced NSCLC combined with bone metastasis patients were collected. Exome sequencing was conducted within 483 tumor-associated genes using Hiseq 2000_PE75 NGS platform...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28223509/high-throughput-screening-of-rare-metabolically-active-tumor-cells-in-pleural-effusion-and-peripheral-blood-of-lung-cancer-patients
#11
Yin Tang, Zhuo Wang, Ziming Li, Jungwoo Kim, Yuliang Deng, Yan Li, James R Heath, Wei Wei, Shun Lu, Qihui Shi
Malignant pleural effusion (MPE), the presence of malignant cells in pleural fluid, is often the first sign of many cancers and occurs in patients with metastatic malignancies. Accurate detection of tumor cells in pleural fluid is crucial because the presence of MPE denotes an advanced stage of disease and directs a switch in clinical managements. Cytology, as a traditional diagnostic tool, has limited sensitivity especially when tumor cells are not abundant, and may be confounded by reactive mesothelial cells in the pleural fluid...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28219200/-application-strategies-of-the-third-generation-egfr-tki-in-the-context-of-precision-medicine
#12
J Zhao, S J Zhang, C C Zhou
With the advances in molecular detection technology and the emergence of various targeted agents, we have entered the era of precision medicine across the whole process of cancer diagnosis and treatment. Tyrosine kinase inhibitors targeting epidermal growth factor receptor gene mutation, the most common driver, have been developed from the first generation to the third generation, improving the survival and life quality of patients with advanced non-small cell lung cancer. It is critically important how to rank these targeted agents and arrange combination therapies, and this review will focus on the strategies of the third-generation EGFR-TKI in the context of precision medicine...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28217439/egfr-targeted-therapy-in-lung-cancer-an-evolving-story
#13
C Bartholomew, L Eastlake, P Dunn, D Yiannakis
Specific oncogenes with driver mutations, such as the Epidermal Growth Factor Receptor (EGFR 1) gene can lead to non-small-cell lung cancer formation. Identification of these oncogenes, their driver mutations and downstream effects allow the targeting of these pathways by drugs. Such personalised therapy has become an important strategy in combating lung cancer and highlights the need to test for these mutations. Tyrosine Kinase Inhibitors (TKIs) against EGFR, such as Erlotinib, are able to halt these tumour promoting properties in non-small-cell lung cancers...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28192371/somatic-mutations-in-telomerase-promoter-counterbalance-germline-loss-of-function-mutations
#14
Lindley Maryoung, Yangbo Yue, Ashley Young, Chad A Newton, Cindy Barba, Nicolai S C van Oers, Richard C Wang, Christine Kim Garcia
Germline coding mutations in different telomere-related genes have been linked to autosomal-dominant familial pulmonary fibrosis. Individuals with these inherited mutations demonstrate incomplete penetrance of clinical phenotypes affecting the lung, blood, liver, skin, and other organs. Here, we describe the somatic acquisition of promoter mutations in telomerase reverse transcriptase (TERT) in blood leukocytes of approximately 5% of individuals with inherited loss-of-function coding mutations in TERT or poly(A)-specific ribonuclease (PARN), another gene linked to telomerase function...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28185792/randomized-phase-iii-study-of-docetaxel-plus-cisplatin-versus-pemetrexed-plus-cisplatin-as-first-line-treatment-of-nonsquamous-non-small-cell-lung-cancer-a-trail-trial
#15
Cheol-Kyu Park, In-Jae Oh, Kyu-Sik Kim, Yoo-Duk Choi, Tae-Won Jang, Youn-Seup Kim, Kwan-Ho Lee, Kyeong-Cheol Shin, Chi Young Jung, Sei-Hoon Yang, Jeong-Seon Ryu, Seung-Hun Jang, Seung-Soo Yoo, Suk-Joong Yong, Kye Young Lee, Kwang-Ho In, Min-Ki Lee, Young-Chul Kim
INTRODUCTION: To date, no prospective phase III trials have directly compared the efficacy of pemetrexed plus cisplatin (Pem-Cis) with docetaxel plus cisplatin (Doc-Cis) in patients with nonsquamous non-small-cell lung cancer. MATERIALS AND METHODS: A total of 148 chemotherapy-naive patients lacking driver mutations were randomized into 21-day regimens of cisplatin 70 mg/m(2) with either docetaxel 60 mg/m(2) (n = 71) or pemetrexed 500 mg/m(2) (n = 77) for ≤ 4 cycles...
January 11, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28179026/proportion-and-clinical-features-of-never-smokers-with-non-small-cell-lung-cancer
#16
Jaeyoung Cho, Sun Mi Choi, Jinwoo Lee, Chang-Hoon Lee, Sang-Min Lee, Dong-Wan Kim, Jae-Joon Yim, Young Tae Kim, Chul-Gyu Yoo, Young Whan Kim, Sung Koo Han, Young Sik Park
BACKGROUND: The proportion of never-smokers with non-small cell lung cancer (NSCLC) is increasing, but that in Korea has not been well addressed in a large population. We aimed to evaluate the proportion and clinical features of never-smokers with NSCLC in a large single institution. METHODS: We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December 2014. RESULTS: Of the 1860 NSCLC patients, 707 (38...
February 8, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28176910/apatinib-as-post-second-line-therapy-in-egfr-wild-type-and-alk-negative-advanced-lung-adenocarcinoma
#17
Shen-Cun Fang, Hai-Tao Zhang, Ying-Ming Zhang, Wei-Ping Xie
In the absence of a driver mutation, chemotherapy is the standard treatment option as first- and second-line therapy for advanced non-small-cell lung cancer (NSCLC). Though a large number of patients are suitable for post second-line therapies, the quality and quantity of the available drugs in this setting is poor. Apatinib, a small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, is a first-generation oral antiangiogenesis drug approved in the People's Republic of China for use as a subsequent line of treatment for advanced gastric cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28174389/-molecular-biology-for-surgical-treatment-of-lung-cancer
#18
Kenichi Suda, Tetsuya Mitsudomi
Progress in lung cancer research achieved during the last 10 years was summarized. These include identification of novel driver mutations and application of targeted therapies, resistance mechanisms to targeted therapies, and immunotherapy with immune checkpoint inhibitors. Molecular biology also affects the field of surgical treatment. Several molecular markers have been reported to predict benign/ malignant or stable/growing tumors, although far from clinical application. In perioperative period, there is a possibility of atrial natriuretic peptide to prevent cancer metastasis...
January 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28167502/a-genetic-interaction-analysis-identifies-cancer-drivers-that-modify-egfr-dependency
#19
Sida Liao, Teresa Davoli, Yumei Leng, Mamie Z Li, Qikai Xu, Stephen J Elledge
A large number of cancer drivers have been identified through tumor sequencing efforts, but how they interact and the degree to which they can substitute for each other have not been systematically explored. To comprehensively investigate how cancer drivers genetically interact, we searched for modifiers of epidermal growth factor receptor (EGFR) dependency by performing CRISPR, shRNA, and expression screens in a non-small cell lung cancer (NSCLC) model. We elucidated a broad spectrum of tumor suppressor genes (TSGs) and oncogenes (OGs) that can genetically modify proliferation and survival of cancer cells when EGFR signaling is altered...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28167203/erbb2-mutated-metastatic-non-small-cell-lung-cancer-response-and-resistance-to-targeted-therapies
#20
Jody C Chuang, Henning Stehr, Ying Liang, Millie Das, Jane Huang, Maximilian Diehn, Heather A Wakelee, Joel W Neal
INTRODUCTION: Erb-b2 receptor tyrosine kinase 2 gene (ERBB2) (also called HER2) has long been recognized as an oncogenic driver in some breast and gastroesophageal cancers in which amplification of this gene confers sensitivity to treatment with Erb-b2 receptor tyrosine kinase 2 (ERBB2)-directed agents. More recently, somatic mutations in ERBB2 have been reported in 1% to 2% of patients with lung adenocarcinoma. Previous case series have suggested clinical tumor responses using anti-ERBB2 small molecules and antibody therapies...
February 4, 2017: Journal of Thoracic Oncology
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