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BRAF lung

Matthew Dankner, April A N Rose, Shivshankari Rajkumar, Peter M Siegel, Ian R Watson
The RAS-RAF-MEK-ERK signaling cascade is among the most frequently mutated pathways in human cancer. Approximately 50% of melanoma patients possess a druggable hotspot V600E/K mutation in the BRAF protein kinase. FDA-approved combination therapies of BRAF and MEK inhibitors are available that provide survival benefits to patients with a BRAF V600 mutation. Non-V600 BRAF mutants are found in many cancers, and are more prevalent than V600 mutations in certain tumor types. For example, between 50-80% of BRAF mutations in non-small cell lung cancer and 22-30% in colorectal cancer encode for non-V600 mutants...
March 15, 2018: Oncogene
Véronique Hofman, Sandra Lassalle, Coraline Bence, Elodie Long-Mira, Sacha Nahon-Estève, Simon Heeke, Virginie Lespinet-Fabre, Catherine Butori, Marius Ilié, Paul Hofman
The identification of certain genomic alterations ( EGFR , ALK , ROS1 , BRAF ) or immunological markers (PD-L1) in tissues or cells has led to targeted treatment for patients presenting with late stage or metastatic lung cancer. These biomarkers can be detected by immunohistochemistry (IHC) and/or by molecular biology (MB) techniques. These approaches are often complementary but depending on, the quantity and quality of the biological material, the urgency to get the results, the access to technological platforms, the financial resources and the expertise of the team, the choice of the approach can be questioned...
March 13, 2018: Cancers
Helena Yu, Ken Suzawa, Emmet J Jordan, Ahmet Zehir, Andy Ni, Hyunjae Ryan Kim, Mark G Kris, Matthew D Hellmann, Bob T Li, Romel Somwar, David B Solit, Michael F Berger, Maria E Arcila, Gregory J Riely, Marc Ladanyi
PURPOSE: To identify molecular factors that determine duration of response to EGFR tyrosine kinase inhibitors and to identify novel mechanisms of drug resistance, we molecularly profiled EGFR mutant tumors prior to treatment and after progression on EGFR TKI using targeted next-generation sequencing.      Experimental Design: Targeted next-generation sequencing was performed on 374 consecutive patients with metastatic EGFR mutant lung cancer. Clinical data were collected and correlated with somatic mutation data...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Li Sun, Zhicheng Xiong, Chengbo Han
In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC...
February 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Weihua Li, Tian Qiu, Yun Ling, Shugeng Gao, Jianming Ying
Next-generation sequencing (NGS) has recently been rapidly adopted in the molecular diagnosis of cancer, but it still faces some obstacles. In this study, 665 lung adenocarcinoma samples (558 TKI-naive and 107 TKI-relapsed samples) were interrogated using NGS, and the challenges and possible solutions of subjecting appropriate tissue samples to NGS testing were explored. The results showed that lower frequencies of HER2/BRAF/PIK3CA and acquired EGFR T790M mutations were observed in biopsy samples with <20% tumor cellularity than those with ≥20%, but there were no significant differences in the frequencies of EGFR or KRAS mutations...
March 8, 2018: Molecular Oncology
Anand A Dalal, Annie Guerin, Alex Mutebi, Kenneth W Culver
AIMS: To assess the time to BRAF testing, compare the characteristics of tested versus not-tested patients, and describe the costs for sequential versus next-generation sequencing (NGS) BRAF testing. METHODS: Patients diagnosed with lung cancer after 12/1/2013 were identified from two US claims databases; their characteristics were assessed during the 12 months before diagnosis (index date). Testing modalities were analyzed from the index date to end of continuous health plan enrollment or data availability (12/2015) based on combinations of Current Procedural Terminology (CPT) procedure codes...
March 8, 2018: Journal of Medical Economics
Shoko Nakasone, Sachiyo Mimaki, Tomohiro Ichikawa, Keiju Aokage, Tomohiro Miyoshi, Masato Sugano, Motohiro Kojima, Satoshi Fujii, Takeshi Kuwata, Atsushi Ochiai, Masahiro Tsuboi, Koichi Goto, Katsuya Tsuchihara, Genichiro Ishii
PURPOSE: Podoplanin-positive cancer-associated fibroblasts (CAFs) play an essential role in tumor progression. However, it is still unclear whether specific genomic alterations of cancer cells are required to recruit podoplanin-positive CAFs. The aim of this study was to investigate the relationship between the mutation status of lung adenocarcinoma cells and the presence of podoplanin-positive CAFs. METHODS: Ninety-seven lung adenocarcinomas for which whole exome sequencing data were available were enrolled...
March 6, 2018: Journal of Cancer Research and Clinical Oncology
Witold Owczarek, Monika Słowińska, Aleksandra Lesiak, Magdalena Ciążyńska, Aldona Maciąg, Elwira Paluchowska, Luiza Marek-Józefowicz, Rafał Czajkowski
Overexpression of the epidermal growth factor receptor (EGFR) is found in many cancers, including those of the head and neck area, non-small-cell lung cancer, and colorectal, cervical, prostate, breast, ovary, stomach, and pancreatic cancer. The EGFR inhibitors are used at present in the treatment of such cancers. Skin lesions that develop during and after cancer treatment may be due to specific cytostatics, molecular-targeted drugs, radiation therapy, complementary therapy, or the cancer itself, and hence knowledge is essential to distinguish between them...
October 2017: Postȩpy Dermatologii i Alergologii
B Melosky, N Blais, P Cheema, C Couture, R Juergens, S Kamel-Reid, M-S Tsao, P Wheatley-Price, Z Xu, D N Ionescu
Background: The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor ( EGFR ) inhibitors, is the standard of care in Canada and many parts of the world. Methods: A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR , anaplastic lymphoma kinase ( ALK ), ROS1 , BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression...
February 2018: Current Oncology
Mark Kriegsmann, Alexander Harms, Daniel Kazdal, Sebastian Fischer, Albrecht Stenzinger, Jonas Leichsenring, Roland Penzel, Rémi Longuespée, Katharina Kriegsmann, Thomas Muley, Seyer Safi, Arne Warth
In the last decade it became evident that many lung adenocarcinomas (ADC) harbor key genetic alterations such as KRAS, EGFR or BRAF mutations as well as rearrangements of ROS1 or ALK that drive these tumors. In the present study we investigated whether different driver mutations of ADC result in different proliferation rates, which might have clinical impact, including resistance to therapy, recurrence and prognosis. We analyzed the proliferation index (PI) on full slides of surgically resected ADC (n = 230) with known genetic aberrations by means of immunohistochemistry and subsequent digital image analysis and correlated the results with clinicopathological variables including overall (OS) and disease free survival (DFS)...
January 2, 2018: Pathology, Research and Practice
Florentia Dimitriou, Anna L Frauchiger, Mirjana Urosevic-Maiwald, Mirjam C Naegeli, Simone M Goldinger, Marjam Barysch, Daniel Franzen, Jivko Kamarachev, Ralph Braun, Reinhard Dummer, Joanna Mangana
The development of cancer immunotherapy and targeted therapy has reached an important inflection point in the history of melanoma. Immune checkpoint inhibitors and kinase inhibitors are today's standard of care treatments in advanced melanoma patients. Treatment-related toxicities can be very intriguing and quite challenging. Sarcoidosis is a multisystemic granulomatous disease characterized by an aberrant immune response to unknown antigens, whereas sarcoid-like reactions (SLRs) refer to localized clinical features...
February 26, 2018: Melanoma Research
Xiu-Fen Liu, Ji-Long Hao, Tian Xie, Om Prakash Pant, Cheng-Bo Lu, Cheng-Wei Lu, Dan-Dan Zhou
Long non-coding RNAs (lncRNAs) participate in the complex network of cancer and play an important role in tumourigenesis and progression. BRAF activated non-coding RNA (BANCR), a 4-exon transcript of 693-bp, was first discovered as an oncogenic long non-coding RNA in BRAFV 600E melanomas cells in 2012 and was related to melanoma cell migration. Besides melanoma, increasing evidence has explored the potential role of BANCR in the development and progression of multiple other human malignancies, such as retinoblastoma, lung cancer, gastric cancer etc...
February 27, 2018: Cell Proliferation
Bo Lan, Chengxi Ma, Chengyan Zhang, Shoujie Chai, Pingli Wang, Liren Ding, Kai Wang
Objective: To assess the association between PD-L1 expression and driver gene mutations in patients with non-small-cell lung cancer (NSCLC). Method: We performed a meta-analysis of 26 studies (7541 patients) which were published from 2015 to 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated to describe the correlation. Subgroup analysis was performed based on population characteristics, types of PD-L1 antibodies and quality of individual studies...
January 26, 2018: Oncotarget
Magda Zanelli, Maxwell Smith, Maria Cecilia Mengoli, Lucia Spaggiari, Loredana De Marco, Filippo Lococo, Francesco Puma, Stefano Ascani
Erdheim Chester disease represents a clonal systemic proliferation of histiocytes. Bone is the most common site of involvement, although virtually any organ, including lungs, can be affected. The diagnosis of Erdheim Chester disease can be difficult due to its rarity and protean presentation. The correlation between clinical, radiological and histological findings is mandatory for the identification of the disease. Foamy histiocytes, lacking Langerhans cells markers, represent the typical histological findings, although their absence does not rule out Erdheim Chester disease...
February 22, 2018: Histopathology
Yang Yang, Yi Meng, Hang Zhang, Xiaoyan Shen, Rutian Li, Lixia Yu, Baorui Liu, Lifeng Wang
Epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitors are the standard first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) expressing sensitive EGFR-mutants. Other drugs target different driver mutants, including the serine/threonine-protein kinase B-raf (BRAF) inhibitor dabrafenib, which has exhibited promising efficacy for treating patients with metastatic BRAF-mutated NSCLC. Therefore, identifying patients carrying mutations that may be treated using targeted therapies is important...
March 2018: Oncology Letters
Jing Zhao, Xiaotong Chen, J Zheng, M Kong, B Wang, W Ding
BACKGROUND: ROS1 immunohistochemistry (IHC) using D4D6 antibody is a useful tool for screening patients with non-small cell lung cancer (NSCLC) slated for targeted therapy. Many studies and our data have identified cases that express the ROS1 protein strongly but are negative for ROS1 by fluorescent in situ hybridization (FISH). The present study investigated the driver mutation and clinicopathologic characteristics of 26 discordant cases (ROS1 IHC-positive but FISH-negative) to find new clues for distinguishing real ROS1-rearranged cases...
February 21, 2018: Histopathology
Zahra Shajani-Yi, Francine B de Abreu, Jason D Peterson, Gregory J Tsongalis
The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective...
February 13, 2018: Neoplasia: An International Journal for Oncology Research
Vincent L Cannataro, Stephen G Gaffney, Carly Stender, Zi-Ming Zhao, Mark Philips, Andrew E Greenstein, Jeffrey P Townsend
Activating mutations in RAS genes are associated with approximately 20% of all human cancers. New targeted therapies show preclinical promise in inhibiting the KRAS G12C variant. However, concerns exist regarding the effectiveness of such therapies in vivo given the possibilities of existing intratumor heterogeneity or de novo mutation leading to treatment resistance. We performed deep sequencing of 27 KRAS G12-positive lung tumors to determine the prevalence of other oncogenic mutations within KRAS or within commonly mutated downstream genes that could confer resistance at the time of treatment...
February 16, 2018: Oncogene
Hironao Yasuoka, Yasushi Nakamura, Ken-Ichi Yoshida, Toshiro Shimo, Masayuki Tori, Yuuki Matsui, Yasushi Sakamaki, Masahiko Tsujimoto
A rare case of a metastatic ectopic papillary thyroid carcinoma (PTC) of the lung that transformed into a squamous cell carcinoma (SCC) that resembles pulmonary SCC is reported. A subcutaneous ectopic PTC in the left anterior neck area, together with a normal thyroid gland, were excised. The ectopic PTC showed thyroglobulin, TTF-1 and PAX-8 immunoreactivity and a BRAF V600E mutation. During the post-operative follow-up period, a rapidly growing 2 cm nodular lesion in the lower left lobe of the lung was detected...
February 16, 2018: Pathology International
P Carassai, G Jocollé, G Donati, S Spinazzé, C Baiocco, P Baderna, A Martinet, F Lococo, F Migliaccio, G Rossi
BRAF mutations occur in about 3% of all lung adenocarcinomas and V600E missense mutation characterizes about half of BRAF -mutated lung adenocarcinomas and is significantly associated with micropapillary pattern and shorter disease-free and overall survival rates. In this report, we report a challenging case of a patient with a metastatic micropapillary adenocarcinoma of the lung harbouring V600E BRAF mutation who experienced a surprising protracted clinical response to metronomic vinorelbine. The possible association between the V600E BRAF mutation pathway and the effective use of vinca alkaloid is discussed...
December 2017: Pathologica
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