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https://www.readbyqxmd.com/read/28919011/dabrafenib-plus-trametinib-in-patients-with-previously-untreated-braf-v600e-mutant-metastatic-non-small-cell-lung-cancer-an-open-label-phase-2-trial
#1
David Planchard, Egbert F Smit, Harry J M Groen, Julien Mazieres, Benjamin Besse, Åslaug Helland, Vanessa Giannone, Anthony M D'Amelio, Pingkuan Zhang, Bijoyesh Mookerjee, Bruce E Johnson
BACKGROUND: BRAF(V600E) mutation occurs in 1-2% of lung adenocarcinomas and acts as an oncogenic driver. Dabrafenib, alone or combined with trametinib, has shown substantial antitumour activity in patients with previously treated BRAF(V600E)-mutant metastatic non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of dabrafenib plus trametinib treatment in previously untreated patients with BRAF(V600E)-mutant metastatic NSCLC. METHODS: In this phase 2, sequentially enrolled, multicohort, multicentre, non-randomised, open-label study, adults (≥18 years of age) with previously untreated metastatic BRAF(V600E)-mutant NSCLC were enrolled into cohort C from 19 centres in eight countries within North America, Europe, and Asia...
September 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28917254/stereotactic-radiotherapy-in-oligometastatic-cancer
#2
Thomas A C Kennedy, Mark T Corkum, Alexander V Louie
Oligometastatic cancer describes a disease state somewhere between localized and metastatic cancer. Proposed definitions of oligometastatic disease have typically used a cut-off of five or fewer sites of disease. Treatment of oligometastatic disease should have the goal of long-term local control, and in selected cases, disease remission. While several retrospective cohorts argue for surgical excision of limited metastases (metastasectomy) as the preferred treatment option for several clinical indications, limited randomized data exists for treating oligometastases...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28915676/clinical-outcomes-of-wbrt-plus-egfr-tkis-versus-wbrt-or-tkis-alone-for-the-treatment-of-cerebral-metastatic-nsclc-patients-a-meta-analysis
#3
Hong Zheng, Quan-Xing Liu, Bin Hou, Dong Zhou, Jing-Meng Li, Xiao Lu, Qiu-Ping Wu, Ji-Gang Dai
Whether WBRT plus EGFR-TKIs has a greater survival benefit than EGFR-TKIs alone or WBRT alone remains controversial in NSCLC patients with multiple brain metastases. To rectify this, we conducted a systematic meta-analysis based on 9 retrospective studies and 1 randomized controlled study published between 2012 and 2016, comprising 1041 patients. Five studies were included in the comparison of WBRT plus EGFR-TKIs and EGFR-TKIs alone. The combined HR for OS of patients with EGFR mutation was 1.25 [95% CI 0.98-2...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915603/estrogen-promotes-tumor-metastasis-via-estrogen-receptor-beta-mediated-regulation-of-matrix-metalloproteinase-2-in-non-small-cell-lung-cancer
#4
Sheng Fan, Yongde Liao, Changyu Liu, Quanfu Huang, Huifang Liang, Bo Ai, Shegnling Fu, Sheng Zhou
In non-small cell lung cancer (NSCLC), estrogen significantly promotes NSCLC cell growth via estrogen receptor beta (ERβ). However, the effects by which ERβ contributes to metastasis in NSCLC have not been previously reported. This study aims at defining whether the stimulation of ERβ promotes NSCLC metastasis in vitro and in vivo. Here, Our results showed that estrogen and ERβ agonist enhanced aggressiveness of two lung cancer cell lines (A549 and H1793) and promoted murine lung metastasis formation. ER-inhibitor Fulvestrant treatment or ERβ-knockdown significantly suppressed the migration, invasion and nodule formation of NSCLC cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904891/clinical-utility-of-circulating-tumor-cells-in-patients-with-non-small-cell-lung-cancer
#5
REVIEW
Marianna Gallo, Antonella De Luca, Monica Rosaria Maiello, Amelia D'Alessio, Claudia Esposito, Nicoletta Chicchinelli, Laura Forgione, Maria Carmela Piccirillo, Gaetano Rocco, Alessandro Morabito, Gerardo Botti, Nicola Normanno
Several different studies have addressed the role of the circulating tumor cells (CTC) in non-small-cell lung cancer (NSCLC). In particular, the potential of CTC analysis in the early diagnosis of NSCLC and in the prediction of the outcome of patients with early and advanced NSCLC have been explored. A major limit of these studies is that they used different techniques for CTC isolation and enumeration, they employed different thresholds to discriminate between high- and low-risk patients, and they enrolled heterogeneous and often small cohort of patients...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28904887/biology-and-clinical-significance-of-circulating-tumor-cell-subpopulations-in-lung-cancer
#6
REVIEW
Linda O'Flaherty, Harriet Wikman, Klaus Pantel
By identifying and tracking genetic changes in primary tumors and metastases, patients can be stratified for the most efficient therapeutic regimen by screening for known biomarkers. However, retrieving tissues biopsies is not always feasible due to tumor location or risk to patient. Therefore, a liquid biopsies approach offers an appealing solution to an otherwise invasive procedure. The rapid growth of the liquid biopsy field has been aided by improvements in the sensitivity and specificity of enrichment assays for isolating circulating tumor cells (CTCs) from normal surrounding blood cells...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28903363/p53-prevent-tumor-invasion-and-metastasis-by-down-regulating-ido-in-lung-cancer
#7
Dongfang Tang, Lu Yue, Ruyong Yao, Lin Zhou, Yuqin Yang, Liming Lu, Wen Gao
In present study, we are to clear demonstrate the genetic evidence of IDO signaling's impact on invasion and metastasis in lung cancer. Here we examined IDO1 expression levels in non-small cell lung cancer (NSCLC) patients (64) tumor/normal pairs underwent RT-PCR and comprehensive histological, immunohistochemica and clinical analysis. The NSCLC cells stably expressing IDO1 was analyzed for migration and invasion assays and the regulatory mechanism in vitro and metastasis assays in vivo. As results, we reported that IDO1 expression increased by more than 3...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901258/from-biology-to-therapy-improvements-of-therapeutic-options-in-lung-cancer
#8
Luigi Formisano, Valerie M Jansen, Roberta Marciano, Roberto Bianco
Lung cancer is the leading cause of cancer-related mortality around the world, despite effective chemotherapeutic agents, the prognosis has remained poor for a long time. The discovery of molecular changes that drive lung cancer has led to a dramatic shift in the therapeutic landscape of this disease. In "in vitro" and "in vivo" models of NSCLC (non-small cell lung cancer), angiogenesis blockade has demonstrated an excellent anti-tumor activity, thus, a number of anti-angiogenic drugs have been approved by regulatory authorities for use in clinical practice...
September 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28893136/investigation-on-the-binding-mechanism-of-loratinib-with-the-c-ros-oncogene-1-ros1-receptor-tyrosine-kinase-via-molecular-dynamics-simulation-and-binding-free-energy-calculations
#9
XiaoYun Wu, YuanYuan Wang, ShanHe Wan, JiaJie Zhang
The c-ros oncogene 1 (ROS1) has proven to be an important cancer target for the treatment of various human cancers. The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been granted approval for the treatment of patients with ROS1 positive metastatic non-small-cell lung cancer (NSCLC) by the Food and Drug Administration (FDA) on 2016. However, serious resistance due to the secondary mutation of glycine 2032 to arginine (G2032R) was developed in clinical studies. Loratinib (PF-06463922), a macrocyclic analogue of crizotinib, showed significantly improved inhibitory activity against wild-type (WT) ROS1 and ROS1(G2032R) mutant...
September 11, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28887531/homogeneity-and-high-concordance-of-alk-translocation-in-primary-lung-adenocarcinoma-and-paired-lymph-node-metastasis
#10
Wei Ma, Lei Guo, Ling Shan, Xiuyun Liu, Ning Lyu, Jianming Ying
Translocation of anaplastic lymphoma kinase (ALK) gene is an important determinator for the response to ALK tyrosine kinase inhibitor (TKI) in non-small-cell lung cancer (NSCLC) patients. The existence of genetic heterogeneity will affect the results of molecular testing, especially in biopsy samples from primary or metastatic sites of patients with advanced stage NSCLC. We intended to explore the heterogeneity of ALK gene translocation in excision specimens and to examine the existence of discordance of ALK status between primary tumours and corresponding lymph node metastases...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28884371/egfr-t790m-mutation-testing-of-non-small-cell-lung-cancer-tissue-and-blood-samples-artificially-spiked-with-circulating-cell-free-tumor-dna-results-of-a-round-robin-trial
#11
Jana Fassunke, Michaela Angelika Ihle, Dido Lenze, Annika Lehmann, Michael Hummel, Claudia Vollbrecht, Roland Penzel, Anna-Lena Volckmar, Albrecht Stenzinger, Volker Endris, Andreas Jung, Ulrich Lehmann, Silke Zeugner, Gustavo Baretton, Hans Kreipe, Peter Schirmacher, Thomas Kirchner, Manfred Dietel, Reinhard Büttner, Sabine Merkelbach-Bruse
The European Commision (EC) recently approved osimertinib for the treatment of adult patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) harboring EGFR T790M mutations. Besides tissue-based testing, blood samples containing cell-free circulating tumor DNA (ctDNA) can be used to interrogate T790M status. Herein, we describe the conditions and results of a round robin trial (RRT) for T790M mutation testing in NSCLC tissue specimens and peripheral blood samples spiked with cell line DNA mimicking tumor-derived ctDNA...
September 8, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28883282/development-of-immune-checkpoint-inhibitors
#12
Shigehisa Kitano
Immune checkpoint inhibitors are the most striking innovation in the clinical development of immunotherapy. Monoclonal antibodies (mAbs) restore and augment the antitumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen-presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of mAb in various cancers. The A first-in-class approved immune checkpoint inhibitor is ipilimumab, which is a fully humanized mAb that blocks the immunosuppressive signal by cytotoxic T-lymphocyte antigen 4...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28881856/strategies-targeting-angiogenesis-in-advanced-non-small-cell-lung-cancer
#13
REVIEW
Jun Wang, Jianpeng Chen, Yan Guo, Baocheng Wang, Huili Chu
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878044/progress-and-prospects-of-early-detection-in-lung-cancer
#14
REVIEW
Sean Blandin Knight, Phil A Crosbie, Haval Balata, Jakub Chudziak, Tracy Hussell, Caroline Dive
Lung cancer is the leading cause of cancer-related death in the world. It is broadly divided into small cell (SCLC, approx. 15% cases) and non-small cell lung cancer (NSCLC, approx. 85% cases). The main histological subtypes of NSCLC are adenocarcinoma and squamous cell carcinoma, with the presence of specific DNA mutations allowing further molecular stratification. If identified at an early stage, surgical resection of NSCLC offers a favourable prognosis, with published case series reporting 5-year survival rates of up to 70% for small, localized tumours (stage I)...
September 2017: Open Biology
https://www.readbyqxmd.com/read/28874890/patterns-of-spread-and-prognostic-implications-of-lung-cancer-metastasis-in-an-era-of-driver-mutations
#15
F Hsu, A De Caluwe, D Anderson, A Nichol, T Toriumi, C Ho
BACKGROUND: In the present study, we examined the pattern of metastatic spread in patients with advanced non-small-cell lung cancer (nsclc) and the effect of EGFR mutations. METHODS: Patients were identified from a provincial cancer registry, and individual medical records were reviewed. Patients were included if they had stage iv nsclc and underwent diagnostic EGFR mutation testing. Patients were divided into EGFR mutation-positive (EGFR+) and EGFR wild type (wt) cohorts...
August 2017: Current Oncology
https://www.readbyqxmd.com/read/28864950/correlation-of-early-pet-findings-with-tumor-response-to-molecular-targeted-agents-in-patients-with-advanced-driver-mutated-non-small-cell-lung-cancer
#16
Tomonobu Koizumi, Toshirou Fukushima, Daisuke Gomi, Takashi Kobayashi, Nodoka Sekiguchi, Keiko Mamiya, Kazunari Tateishi, Akane Katou, Kazuhiro Oguchi
Recent advances in positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) have facilitated not only the diagnosis and staging of lung cancer, but also the prediction of treatment outcome. The present study was designed to assess the usefulness of early FDG-PET examination for predicting subsequent tumor size reduction in response to molecular targeted agents in metastatic non-small cell lung cancer (NSCLC) with sensitive gene anomalies. I. In 29 targeted lesions of 10 NSCLC patients, changes in FDG uptake before and on day 7 after the initiation of molecular targeted therapy (gefitinib, n = 7; crizotinib, n = 3) were compared with subsequent radiographic tumor size reduction by RECIST...
September 1, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28861767/placental-growth-factor-signaling-regulates-isoform-splicing-of-vascular-endothelial-growth-factor-a-in-the-control-of-lung-cancer-cell-metastasis
#17
Zanfeng Wang, Tingwei Liu
Vascular endothelial growth factor (VEGF) family members play critical and complex roles in the regulation of cancer vascularization and metastasis. The exact molecular control of lung cancer metastasis by VEGF family members is not completely understood. Here, we showed that specimens from non-small cell lung cancer (NSCLC) contained significantly higher levels of placental growth factor (PlGF) than paired non-cancer tissue (p < 0.05, N = 25). Moreover, higher levels of PlGF were detected in NSCLC specimens from the patients who had distal metastases than those who had not...
August 31, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28861332/eml4-alk-positive-lung-adenocarcinoma-presenting-an-unusual-metastatic-pattern-in-a-29-year-old-woman-who-is-alive-and-well%C3%A2-in%C3%A2-her-third-year-follow-up-a-case-report
#18
Fatma Tokat, Handan Zeren, Pinar Barut, Sualp Tansan, Umit Ince
Non-small cell lung cancer (NSCLC) is a frequent tumor entity with high mortality. Although several newly discovered chromosomal translocations and mutations opened new horizons for targeted therapy, literature still lacks large series of NSCLC with chromosomal abberations and their correlations with histological and clinical features. We present a case of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation positive adenocarcinoma of the lung with an unusual metastatic pattern in a 29-year-old young woman...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28856088/syndrome-of-inappropriate-secretion-of-anti-diuretic-hormone-siadh-as-an-initial-presenting-sign-of-non-small-cell-lung-cancer-case-report-and-literature-review
#19
Praneet Iyer, Mohammad Ibrahim, Waqas Siddiqui, Ahmed Dirweesh
Association of SIADH with malignancy was first reported in 1957, when it was described in two patients with bronchogenic carcinoma. While the association with small cell lung cancer (SCLC) is well known, that with non small cell lung cancer (NSCLC) has been rarely reported. We report a case of 70 year old male who was found to have hyponatremia secondary to SIADH. Radiological tests revealed right hilar lung mass with mediastinal adenopathy. Bronchoscopic biopsy revealed non-small cell lung cancer of type squamous cell...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28845132/cell-free-dna-in-non-small-cell-lung-cancer
#20
Vaida Gedvilaitė, Diana Schveigert, Saulius Cicėnas
Lung cancer is the leading cause of cancer-associated deaths worldwide. Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC). Advances in the knowledge of the biology of non-small cell lung cancer have revealed molecular information used for systemic cancer therapy targeting metastatic disease, with an important impact on patients' overall survival (OS) and quality of life. However, a biopsy of overt metastases is an invasive procedure limited to certain locations and not easily acceptable in the clinic...
2017: Acta medica Lituanica
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