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https://www.readbyqxmd.com/read/28631135/long-term-clinical-benefit-from-salvage-egfr-tyrosine-kinase-inhibitors-in-advanced-non-small-cell-lung-cancer-patients-with-egfr-wild-type-tumors
#1
F Koinis, A Voutsina, A Kalikaki, A Koutsopoulos, E Lagoudaki, E Tsakalaki, E K Dermitzaki, E Kontopodis, A G Pallis, V Georgoulias, A Kotsakis
BACKGROUND: Erlotinib has been approved for the management of NSCLC patients after failure of the first or subsequent line of chemotherapy. Although the efficacy of erlotinib is clearly associated with the presence of EGFR mutations, there is a subset of patients with EGFR wild-type (EGFRwt) tumors who impressively respond. PATIENTS AND METHODS: Patients with EGFRwt NSCLC who received salvage (≥2nd line) treatment with erlotinib for a prolonged period (>6 months), were sought from the database of the Hellenic Oncology Research Group...
June 19, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28625649/investigation-of-patterns-of-nodal-metastases-in-braf-mutant-lung-cancer
#2
S H McEvoy, D F Halpenny, A Viteri-Jusué, S A Hayes, A J Plodkowski, G J Riely, M S Ginsberg
Axillary lymph nodes (axLN) are a rare site of nodal metastases in patients with lung cancer. BRAF mutated lung cancer is a genetically distinct subtype that occurs in 2-5% of non-small cell lung carcinomas (NSCLC). A recent study identified a highly unusual pattern of metastatic spread to axLN in patients with BRAF mutated colorectal cancer (CRC). The purpose of the study is to assess the incidence of axLN metastases in BRAF mutated NSCLC. Baseline computed tomography (CT) imaging at diagnosis and all follow up CTs of patients with BRAF mutated NSCLC treated at our institution were retrospectively reviewed by two radiologists for evidence of axLN metastases...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28619094/morphologic-and-molecular-study-of-lung-cancers-associated-with-idiopathic-pulmonary-fibrosis-and-other-pulmonary-fibroses
#3
Alice Guyard, Claire Danel, Nathalie Théou-Anton, Marie-Pierre Debray, Laure Gibault, Pierre Mordant, Yves Castier, Bruno Crestani, Gérard Zalcman, Hélène Blons, Aurélie Cazes
BACKGROUND: Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS). METHODS: Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group...
June 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28608966/next-generation-sequencing-and-clinical-outcomes-of-patients-with-lung-adenocarcinoma-treated-with-stereotactic-body-radiotherapy
#4
Richard J Cassidy, Xinyan Zhang, Pretesh R Patel, Joseph W Shelton, Chase E Escott, Gabriel L Sica, Michael R Rossi, Charles E Hill, Conor E Steuer, Rathi N Pillai, Suresh S Ramalingam, Taofeek K Owonikoko, Madhusmita Behera, Seth D Force, Felix G Fernandez, Walter J Curran, Kristin A Higgins
BACKGROUND: Genetic aberrations are well characterized in lung adenocarcinomas (LACs) and clinical outcomes have been influenced by targeted therapies in the advanced setting. Stereotactic body radiotherapy (SBRT) is the standard-of-care therapy for patients with nonoperable, early-stage LAC, but to the authors' knowledge, no information is available regarding the impact of genomic changes in these patients. The current study sought to determine the frequency and clinical impact of genetic aberrations in this population...
June 13, 2017: Cancer
https://www.readbyqxmd.com/read/28607685/concurrent-braf-and-pten-mutations-in-melanoma-of-unknown-origin-presenting-as-a-breast-mass
#5
Emmanuel Agosto-Arroyo, Marilin Rosa, Alec Chau, Laila Khazai
BACKGROUND: Metastases represent a small percentage of the malignancies affecting the breast, and only 5% of melanomas originate from non-cutaneous sites. Multiple genetic aberrations have been associated with the development of melanocytic lesions, including BRAF V600E mutation. Mutations in PTEN gene have also been related to the pathogenesis of multiple malignancies. PURPOSE/METHOD: This is the case of a 28-year-old female who presented with a tender, palpable mass in the upper outer quadrant of the right breast...
2017: SAGE open medical case reports
https://www.readbyqxmd.com/read/28586760/clinical-mutational-profiling-of-1006-lung-cancers-by-next-generation-sequencing
#6
Peter B Illei, Deborah Belchis, Li-Hui Tseng, Doreen Nguyen, Federico De Marchi, Lisa Haley, Stacy Riel, Katie Beierl, Gang Zheng, Julie R Brahmer, Frederic B Askin, Christopher D Gocke, James R Eshleman, Patrick M Forde, Ming-Tseh Lin
Analysis of lung adenocarcinomas for actionable mutations has become standard of care. Here, we report our experience using next generation sequencing (NGS) to examine AKT1, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes in 1006 non-small cell lung cancers in a clinical diagnostic setting. NGS demonstrated high sensitivity. Among 760 mutations detected, the variant allele frequency (VAF) was 2-5% in 33 (4.3%) mutations and 2-10% in 101 (13%) mutations. A single bioinformatics pipeline using Torrent Variant Caller, however, missed a variety of EGFR mutations...
May 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28584208/establishment-of-a-novel-method-for-screening-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-resistance-mutations-in-lung-cancer
#7
Hong-Xia Tian, Xu-Chao Zhang, Zhen Wang, Jin-Ji Yang, Wei-Bang Guo, Zhi-Hong Chen, Yi-Long Wu
BACKGROUND: Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform...
June 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28577958/lepidic-predominant-adenocarcinoma-and-invasive-mucinous-adenocarcinoma-of-the-lung-exhibit-specific-mucin-expression-in-relation-with-oncogenic-drivers
#8
Duruisseaux Michaël, Antoine Martine, Rabbe Nathalie, Rodenas Anita, Mc Leer-Florin Anne, Lacave Roger, Poulot Virginie, Duchêne Belinda, Van Seuningen Isabelle, Cadranel Jacques, Wislez Marie
OBJECTIVES: To evaluate MUC1, MUC2, MUC5B, MUC5AC, and MUC6 expression in invasive lepidic predominant adenocarcinoma (LPA) and invasive mucinous adenocarcinoma (IMA) of the lung, and the impact of oncogenic drivers. MATERIALS AND METHODS: MUC1, MUC2, MUC5B, MUC5AC, MUC6, TTF1 and Hnf4α immunohistochemistry was performed on surgical samples from 52 patients with IMA (n=25) or LPA (n=27). We searched for EGFR, KRAS, BRAF, and HER2 mutations and ALK, ROS1, and NRG1 rearrangements...
July 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28572536/the-detection-and-significance-of-egfr-and-braf-in-cell-free-dna-of-peripheral-blood-in-nsclc
#9
Yang Yang, Xiaoyan Shen, Rutian Li, Jie Shen, Hang Zhang, Lixia Yu, Baorui Liu, Lifeng Wang
OBJECTIVE: Although driver mutation status is crucial to targeted therapy decision-making in non-small cell lung cancer (NSCLC), due to unavailable or inadequate biopsies, there are still many patients with unknown mutation status. A promising way to solve this problem is liquid biopsy, such as cell-free DNA (cfDNA) in peripheral blood. Additionally, due to the little amount of cfDNA, detecting methods with high sensitivity, specificity and economy are required in clinical practice. Here, we explored the feasibility of Competitive Allele-Specific TaqMan® PCR (CastPCR) detecting driver mutations in cfDNA from plasma in lung adenocarcinoma patients...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28572531/egfr-g796d-mutation-mediates-resistance-to-osimertinib
#10
Di Zheng, Min Hu, Yu Bai, Xuehua Zhu, Xuesong Lu, Chunyan Wu, Jiying Wang, Li Liu, Zheng Wang, Jian Ni, Zhenfan Yang, Jianfang Xu
Osimertinib is an effective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in multiple countries and regions for patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC). Despite impressive initial tumor responses, development of drug resistance ultimately limits the benefit of this compound. Mechanisms of resistance to osimertinib are just beginning to emerge, such as EGFR C797S and L718Q mutations, BRAF V600E and PIK3CA E545K mutations, as well as ERBB2 and MET amplification...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28558851/-new-biopsy-at-lung-cancer-progression-rational-treatment-of-resistant-lung-cancer
#11
L B M Hijmering-Kappelle, A J van der Wekken, T J N Hiltermann, H J M Groen
Nowadays, patients with advanced non-small cell lung cancer harbouring a driver mutation undergo targeted treatment. This results in profound tumour responses but inevitably induces resistance after approximately 9 to 12 months. In this article we consider the importance and clinical implications of taking new biopsies to retrieve information regarding resistance mechanisms. There is a shift in the use of other modalities such as radiotherapy and surgery in patients with oligometastatic disease, producing long-lasting responses...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28557526/molecular-profiling-of-malignant-pleural-effusion-in-metastatic-non-small-cell-lung-carcinoma-the-effect-of-pre-analytical-factors
#12
Jamal Carter, James Adam Miller, David Feller-Kopman, David Ettinger, David Sidransky, Zahra Maleki
RATIONALE: non-small cell lung cancer (NSCLC)-associated malignant pleural effusions (MPE) are sometimes the only available specimens for molecular analysis. OBJECTIVES: this study evaluates diagnostic yield of NSCLC-associated MPE, its adequacy for immunohistochemistry (IHC) and the potential influence of MPE volume/cellularity on the analytic sensitivity of our assays. METHODS: molecular results of 50 NSCLC-associated MPE cases during a 5-year period were evaluated...
May 30, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28553668/the-clinical-spectrum-of-erdheim-chester-disease-an-observational-cohort-study
#13
Juvianee I Estrada-Veras, Kevin J O'Brien, Louisa C Boyd, Rahul H Dave, Benjamin Durham, Liqiang Xi, Ashkan A Malayeri, Marcus Y Chen, Pamela J Gardner, Jhonell R Alvarado-Enriquez, Nikeith Shah, Omar Abdel-Wahab, Bernadette R Gochuico, Mark Raffeld, Elaine S Jaffe, William A Gahl
Erdheim-Chester Disease (ECD) is a rare, potentially fatal, multi-organ myeloid neoplasm occurring mainly in adults. The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a-, and frequently S100-. The purpose of this report is to describe the clinical and molecular variability of ECD. Sixty consecutive ECD patients (45 males, 15 females) were prospectively evaluated at the NIH Clinical Center between 2011 and 2015. Comprehensive imaging and laboratory studies were performed, and tissues were examined for BRAF V600E and MAPK pathway mutations...
February 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/28550959/coexistence-of-egfr-kras-braf-and-pik3ca-mutations-and-alk-rearrangement-in-a%C3%A2-comprehensive-cohort-of-326-consecutive-spanish-nonsquamous-nsclc-patients
#14
Paloma Martín Martorell, Marisol Huerta, Amparo Compañ Quilis, Rosario Abellán, Enrique Seda, Sebastián Blesa, Felipe J Chaves, Diego Dualde Beltrán, Susana Roselló Keränen, José Franco, Amelia Insa
INTRODUCTION: Molecular screening is crucial for the care of nonsquamous non-small-cell lung cancer (NSCLC) patients. The coexistence of mutations could have important consequences regarding treatment. We described the mutational patterns and coexistence among patients and their outcomes after targeted treatment. MATERIALS AND METHODS: Data from consecutive patients with newly diagnosed nonsquamous NSCLC were prospectively collected. Next-generation sequencing analysis of mutational hotspots in the EGFR, KRAS, PIK3CA, and BRAF genes and analysis of anaplastic lymphoma kinase (ALK) rearrangement were performed...
April 27, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28550040/kras-g12d-expression-in-lung-resident-myeloid-cells-promotes-pulmonary-lch-like-neoplasm-sensitive-to-statin-treatment
#15
Tamihiro Kamata, Susan Giblett, Catrin Pritchard
Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm associated with somatic mutations in the genes involved in the RAF/MEK/ERK signaling pathway. Recently, oncogenic mutations in NRAS/KRAS, upstream regulators of the RAF/MEK/ERK pathway, have been reported in pulmonary, but not in non-pulmonary, LCH cases, suggesting organ-specific contribution of oncogenic RAS to LCH pathogenesis. Using a mouse model expressing KRAS(G12D) in the lung by nasal delivery of adenoviral Cre, here we show that KRAS(G12D) expression in lung-resident myeloid cells induces pulmonary LCH-like neoplasms comprised of pathogenic CD11c(high)F4/80+CD207+ cells...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28544061/survival-difference-according-to-mutation-status-in-a-prospective-cohort-study-of-australian-patients-with-metastatic-non-small-cell-lung-carcinoma-nsclc
#16
Lavinia Tan, Marliese Alexander, Ann Officer, Michael MacManus, Linda Mileshkin, Ross Jennens, Dishan Herath, Richard de Boer, Stephen B Fox, David Ball, Benjamin Solomon
BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histologic subtypes but also different molecular subtypes. Our objective is to describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. METHODS: Metastatic NSCLC patients enrolled onto a prospective Thoracic Malignancies Cohort (TMC) Study between July 2012 and August 2016 were selected...
May 24, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28539463/braf-fusion-as-a-novel-mechanism-of-acquired-resistance-to-vemurafenib-in-braf-v600e-mutant-melanoma
#17
Atul Kulkarni, Husam Al-Hraishawi, Srilatha Simhadri, Kim M Hirshfield, Suzie Chen, Sharon R Pine, Chandrika Jeyamohan, Levi Sokol, Siraj M Ali, Man Lung Teo, Eileen White, Lorna Rodriguez-Rodriguez, Janice M Mehnert, Shridar Ganesan
Many patients with BRAF (V)(600E) mutant melanoma treated with BRAF inhibitors experience a rapid response, but ultimately develop resistance. Insight into the mechanism of resistance is critical for development of more effective treatment strategies. <br /><br />Experimental Design: Comprehensive genomic profiling of serial biopsies was performed in a patient with a BRAF(V600E) mutant metastatic melanoma who developed resistance to vemurafenib. An AGAP3-BRAF fusion gene, identified in the vemurafenib-resistant tumor, was expressed in BRAF(V600E) melanoma cell lines and its effect on drug sensitivity was evaluated...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28538219/molecular-alterations-in-patients-with-pulmonary-adenocarcinoma-presenting-with-malignant-pleural-effusion-at-the-first-diagnosis
#18
Erika F Rodriguez, Maryam Shabihkhani, Jamal Carter, Zahra Maleki
OBJECTIVES: The aim of this study was to report cytologic and molecular features of pulmonary adenocarcinoma patients presenting with a malignant pleural effusion at the first diagnosis. STUDY DESIGN: Patients who had a cytopathologic diagnosis conclusive for lung adenocarcinoma for the first time on their pleural fluid specimen, and molecular testing done, were studied. The control group consisted of patients with a malignant pleural effusion that developed during disease progression...
2017: Acta Cytologica
https://www.readbyqxmd.com/read/28515244/what-when-and-how-of-biomarker-testing-in-non-small-cell-lung-cancer
#19
Gregory L Riely
Biomarker testing is recommended for all patients diagnosed with non-small cell lung cancer. At a minimum, testing should include the mutations/fusions EGFR, ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA-approved therapies are available for these alterations. Other actionable molecular findings include RET rearrangements, BRAF(V600E) mutations, and MET exon 14 alterations. If adequate testing was not performed at treatment initiation, molecular testing should be performed before administration of subsequent lines of therapy...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28500236/identification-of-the-serine-biosynthesis-pathway-as-a-critical-component-of-braf-inhibitor-resistance-of-melanoma-pancreatic-and-non-small-cell-lung-cancer-cells
#20
Kayleigh C Ross, Andrew J Andrews, Christopher D Marion, Timothy J Yen, Vikram Bhattacharjee
Metastatic melanoma cells commonly acquire resistance to BRAF V600E inhibitors (BRAFis). In this study, we identified serine biosynthesis as a critical mechanism of resistance. Proteomic assays revealed differential protein expression of serine biosynthetic enzymes PHGDH, PSPH, and PSAT1 following vemurafenib (BRAFi) treatment in sensitive versus acquired resistant melanoma cells. Ablation of PHGDH via siRNA sensitized acquired resistant cells to vemurafenib. Inhibiting the folate cycle, directly downstream of serine synthesis, with methotrexate also displayed similar sensitization...
May 12, 2017: Molecular Cancer Therapeutics
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