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Egfr kinase

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https://www.readbyqxmd.com/read/28088512/ros1-fusions-rarely-overlap-with-other-oncogenic-drivers-in-non-small-cell-lung-cancer
#1
Jessica J Lin, Lauren L Ritterhouse, Siraj M Ali, Mark Bailey, Alexa B Schrock, Justin F Gainor, Lorin A Ferris, Mari Mino-Kenudson, Vincent A Miller, Anthony J Iafrate, Jochen K Lennerz, Alice T Shaw
INTRODUCTION: Chromosomal rearrangements involving the ROS proto-oncogene 1 receptor tyrosine kinase gene (ROS1) define a distinct molecular subset of non-small cell lung cancer (NSCLC) with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in epidermal growth factor receptor (EGFR) and KRAS proto-oncogene (KRAS). METHODS: We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma kinase (ALK)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#2
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088467/stat3-signaling-mediates-tumour-resistance-to-egfr-targeted-therapeutics
#3
Ahmad A Zulkifli, Fiona H Tan, Tracy L Putoczki, Stanley S Stylli, Rodney B Luwor
Several EGFR inhibitors are currently undergoing clinical assessment or are approved for the clinical management of patients with varying tumour types. However, treatment often results in a lack of response in many patients. The majority of patients that initially respond eventually present with tumours that display acquired resistance to the original therapy. A large number of receptor tyrosine and intracellular kinases have been implicated in driving signaling that mediates this tumour resistance to anti-EGFR targeted therapy, and in a few cases these discoveries have led to overall changes in prospective tumour screening and clinical practice (K-RAS in mCRC and EGFR T790M in NSCLC)...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28086832/norcantharidin-inhibits-cell-growth-by-suppressing-the-expression-and-phosphorylation-of-both-egfr-and-c-met-in-human-colon-cancer-cells
#4
Peiju Qiu, Siwen Wang, Ming Liu, He Ma, Xuan Zeng, Meng Zhang, Lingling Xu, Yidi Cui, Huixin Xu, Yang Tang, Yanli He, Lijuan Zhang
BACKGROUND: Norcantharidin (NCTD) is a Chinese FDA approved, chemically synthesized drug for cancer treatment. The effect of NCTD on signaling proteins of EGFR and c-Met was systematically elucidated in current study. METHODS: Two human colon cancer cell lines, HCT116 and HT29, were used as model systems to investigate the anti-cancer molecular mechanism of NCTD. Cell cycle arrest and early/late apoptosis were analyzed by flow cytometry. The levels of EGFR, phospho-EGFR, c-Met, phospho-c-Met and other related proteins were quantified by western blot analysis...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28079144/igf-ir-cooperates-with-er%C3%AE-to-inhibit-breast-cancer-cell-aggressiveness-by-regulating-the-expression-and-localisation-of-ecm-molecules
#5
Nikolaos A Afratis, Panagiotis Bouris, Spyros S Skandalis, Hinke A Multhaupt, John R Couchman, Achilleas D Theocharis, Nikos K Karamanos
IGF-IR is highly associated with the behaviour of breast cancer cells. In ERα-positive breast cancer, IGF-IR is present at high levels. In clinical practice, prolonged treatment with anti-estrogen agents results in resistance to the therapy with activation of alternative signaling pathways. Receptor Tyrosine Kinases, and especially IGF-IR, have crucial roles in these processes. Here, we report a nodal role of IGF-IR in the regulation of ERα-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix molecules...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079142/the-prognostic-role-of-egfr-tkis-for-patients-with-advanced-non-small-cell-lung-cancer
#6
Dan Zhao, Xuejing Chen, Na Qin, Dan Su, Lijuan Zhou, Quan Zhang, Xi Li, Xinyong Zhang, Mulan Jin, Jinghui Wang
Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077457/systems-biology-derived-biomarkers-to-predict-progression-of-renal-function-decline-in-type-2-diabetes-mellitus
#7
Gert Mayer, Hiddo J L Heerspink, Constantin Aschauer, Andreas Heinzel, Georg Heinze, Alexander Kainz, Judith Sunzenauer, Paul Perco, Dick de Zeeuw, Peter Rossing, Michelle Pena, Rainer Oberbauer
OBJECTIVE: Chronic kidney disease (CKD) in diabetes has a complex molecular and likely multifaceted pathophysiology. We aimed to validate a panel of biomarkers identified using a systems biology approach to predict the individual decline of estimated glomerular filtration rate (eGFR) in a large group of patients with type 2 diabetes mellitus and CKD at various stages. RESEARCH DESIGN AND METHODS: We used publicly available "omics" data to develop a molecular process model of CKD in diabetes and identified a representative parsimonious set of nine molecular biomarkers: chitinase 3-like protein 1, growth hormone 1, hepatocyte growth factor, matrix metalloproteinase (MMP) 2, MMP7, MMP8, MMP13, tyrosine kinase, and tumor necrosis factor receptor-1...
January 11, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28076826/identification-of-new-pyrrolo-2-3-d-pyrimidines-as-src-tyrosine-kinase-inhibitors-in%C3%A2-vitro-active-against-glioblastoma
#8
Francesca Musumeci, Anna Lucia Fallacara, Chiara Brullo, Giancarlo Grossi, Lorenzo Botta, Pierpaolo Calandro, Mario Chiariello, Miroslava Kissova, Emmanuele Crespan, Giovanni Maga, Silvia Schenone
In the last few years, several pyrrolo-pyrimidine derivatives have been either approved by the US FDA and in other countries for the treatment of different diseases or are currently in phase I/II clinical trials. Herein we present the synthesis and the characterization of a novel series of pyrrolo[2,3-d]pyrimidines, compounds 8a-j, and their activity against Glioblastoma multiforme (GBM). Docking studies and MM-GBSA analysis revealed the ability of such compounds to efficiently interact with the ATP binding site of Src...
December 19, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28076323/clinical-outcome-of-tyrosine-kinase-inhibitors-alone-or-combined-with-radiotherapy-for-brain-metastases-from-epidermal-growth-factor-receptor-egfr-mutant-non-small-cell-lung-cancer-nsclc
#9
Qianqian Zhu, Yanan Sun, Yingying Cui, Ke Ye, Chengliang Yang, Daoke Yang, Jie Ma, Xiao Liu, Jinming Yu, Hong Ge
This study compared treatment outcomes between TKI monotherapy and TKI administration combined with brain radiotherapy (TKI + RT) in 133 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). We also evaluated the association of different epidermal growth factor receptor (EGFR) mutation subtypes with treatment outcome. To screen for potential variables affecting cranial progression free survival (PFS) and overall survival (OS), we performed univariate and multivariate analysis based on Cox proportional-hazards models...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075527/recent-development-of-the-second-and-third-generation-irreversible-egfr-inhibitors
#10
REVIEW
Weiwei Han, Yongli Du
Recent reports suggested that essential directions for new lung cancer, breast carcinoma therapies, as well as the roomier realm of targeted cancer therapies were provided through targeting the epidermal growth factor receptor (EGFR). Patients who carrying non-small cell lung carcinoma (NSCLC) with activating mutations in EGFR initially respond well to the EGFR inhibitors erlotinib and gefitinib, which were located the active site of the EGFR kinase and designed to act as competitive inhibitors of combining with the ATP...
January 11, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28074321/predictive-factors-of-early-distant-brain-failure-after-gamma-knife-radiosurgery-alone-in-patients-with-brain-metastases-of-non-small-cell-lung-cancer
#11
Young Cheol Na, Hyun Ho Jung, Hye Ryun Kim, Byoung Chul Cho, Jin Woo Chang, Yong Gou Park, Won Seok Chang
The objective of this study was to elucidate the predictive factors for early distant brain failure in patients with brain metastases of non-small-cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKRS) without previous whole-brain radiotherapy (WBRT) or surgery. We retrospectively reviewed clinical and imaging data of 459 patients with brain metastases of NSCLC who underwent GKRS from June 2008 to December 2013. The primary end-point was early distant brain failure, defined as the detection of newly developed metastatic lesions on magnetic resonance imaging (MRI) 3 months after GKRS...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28073786/phase-1-study-of-twice-weekly-pulse-dose-and-daily-low-dose-erlotinib-as-initial-treatment-for-patients-with-egfr-mutant-lung-cancers
#12
H A Yu, C Sima, D Feldman, L L Liu, B Vaitheesvaran, J Cross, C M Rudin, M G Kris, W Pao, F Michor, G J Riely
BACKGROUND: Patients with EGFR-mutant lung cancers treated with EGFR tyrosine kinase inhibitors (TKIs) develop clinical resistance, most commonly with acquisition of EGFR T790M. Evolutionary modeling suggests that a schedule of twice weekly pulse and daily low-dose erlotinib may delay emergence of EGFR T790M. Pulse dose erlotinib has superior central nervous system (CNS) penetration and may result in superior CNS disease control. METHODS: We evaluated toxicity, pharmacokinetics, and efficacy of twice weekly pulse and daily low-dose erlotinib...
October 25, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28073102/cancer-resistance-to-therapies-against-the-egfr-ras-raf-pathway-the-role-of-mek
#13
REVIEW
Erika Martinelli, Floriana Morgillo, Teresa Troiani, Fortunato Ciardiello
The mitogen-activated protein kinases (MAPKs) mediate intracellular signals activated by a wide variety of extracellular stimuli. The activation of the RAS-RAF-MEK-MAPK cascade culminates in the regulation of gene transcription promoting cancer cell proliferation, survival, migration and angiogenesis. MEK (mitogen-activated protein kinase kinase-MAPKK) 1/2 is a transducer of the growth factor receptor-RAS-RAF-MAPK signalling cascade and plays a relevant role in development and progression of human cancers, such as colorectal cancer (CRC), non small cell lung cancer (NSCLC)...
December 30, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28072464/genistein-and-tyrphostin-ag556-decrease-human-atrial-ultra-rapidly-activating-delayed-rectifier-potassium-current-by-inhibiting-egfr-tyrosine-kinase
#14
Guo-Sheng Xiao, Yan-Hui Zhang, Wei Wu, Hai-Ying Sun, Yan Wang, Gui-Rong Li
BACKGROUND AND PURPOSE: The ultra-rapidly activating delayed rectifier K(+) current IKur (encoded by Kv1.5 or KCNA5) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). EXPERIMENTAL APPROACH: Whole-cell patch voltage-clamp technique, and immunoprecipitation/western blotting analysis were used to investigate whether the PTK inhibitors genistein, Tyrphostin AG556 (AG556) and PP2 regulate human atrial IKur , and hKv1...
January 10, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28068322/role-of-the-pdz-scaffold-protein-nherf1-ebp50-in-cancer-biology-from-signaling-regulation-to-clinical-relevance
#15
REVIEW
J Vaquero, T H Nguyen Ho-Bouldoires, A Clapéron, L Fouassier
The transmission of cellular information requires fine and subtle regulation of proteins that need to interact in a coordinated and specific way to form efficient signaling networks. The spatial and temporal coordination relies on scaffold proteins. Thanks to protein interaction domains such as PDZ domains, scaffold proteins organize multiprotein complexes enabling the proper transmission of cellular information through intracellular networks. NHERF1/EBP50 is a PDZ-scaffold protein that was initially identified as an organizer and regulator of transporters and channels at the apical side of epithelia through actin-binding ezrin-moesin-radixin proteins...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28066597/the-impact-of-smoking-status-on-radiologic-tumor-progression-patterns-and-response-to-epidermal-growth-factor-receptor-egfr-tyrosine-kinase-inhibitors-in-lung-adenocarcinoma-with-activating-egfr-mutations
#16
Yoon Ki Cha, Ho Yun Lee, Myung-Ju Ahn, Keunchil Park, Jin Seok Ahn, Jong-Mu Sun, Yoon-La Choi, Kyung Soo Lee
BACKGROUND: The aim of this study was to evaluate the impact of smoking on the treatment outcome of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant lung adenocarcinoma, with consideration of other factors including radiologic tumor progression pattern according to patient smoking status. METHODS: A total of 224 patients with EGFR mutant lung adenocarcinomas that were treated with EGFR-TKIs were retrospectively reviewed...
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28065855/tyrosine-kinase-phosphatase-inhibitors-decrease-dengue-virus-production-in-hepg2-cells
#17
Thawornchai Limjindaporn, Jutatip Panaampon, Shilu Malakar, Sansanee Noisakran, Pathai Yenchitsomanus
Dengue virus is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. High rates of dengue virus replication and virion production are related to disease severity. To identify anti-DENV compounds, we performed cell-based ELISA testing to detect the level of DENV E protein expression. Among a total of 83 inhibitors, eight were identified as inhibitors with antiviral activity. Epidermal growth factor receptor inhibitor II (EGFR/ErbB-2/ErbB-4 inhibitor II) and protein tyrosine phosphatase inhibitor IV (PTP inhibitor IV) significantly inhibited dengue virus production and demonstrated low toxicity in hepatocyte cell lines...
January 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28065789/choline-kinase-alpha-mediates-interactions-between-the-epidermal-growth-factor-receptor-and-mtorc2-in-hepatocellular-carcinoma-cells-to-promote-drug-resistance-and-xenograft-tumor-progression
#18
Xi-Meng Lin, Liang Hu, Jin Gu, Ruo-Yu Wang, Liang Li, Jing Tang, Bao-Hua Zhang, Xing-Zhou Yan, Yan-Jing Zhu, Cong-Li Hu, Wei-Ping Zhou, Shao Li, Jing-Feng Liu, Frank J Gonzalez, Meng-Chao Wu, Hong-Yang Wang, Lei Chen
BACKGROUND & AIMS: Choline kinase alpha (CHKA) catalyzes conversion of choline to phosphocholine and can contribute to carcinogenesis. Little is known about the role of CHKA in the pathogenesis of hepatocellular carcinoma (HCC). METHODS: We performed whole-exome and transcriptome sequence analyses of 9 paired HCC and non-tumor adjacent tissues. We performed tissue chip analyses of 120 primary HCC and non-tumor adjacent tissues from patients who received surgery in Shanghai, China from January 2006 through December 2009; 48 sets of specimens (HCC and non-tumor adjacent tissues) were also analyzed...
January 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28065597/a-global-analysis-of-the-receptor-tyrosine-kinase-protein-phosphatase-interactome
#19
Zhong Yao, Katelyn Darowski, Nicole St-Denis, Victoria Wong, Fabian Offensperger, Annabel Villedieu, Shahreen Amin, Ramy Malty, Hiroyuki Aoki, Hongbo Guo, Yang Xu, Caterina Iorio, Max Kotlyar, Andrew Emili, Igor Jurisica, Benjamin G Neel, Mohan Babu, Anne-Claude Gingras, Igor Stagljar
Receptor tyrosine kinases (RTKs) and protein phosphatases comprise protein families that play crucial roles in cell signaling. We used two protein-protein interaction (PPI) approaches, the membrane yeast two-hybrid (MYTH) and the mammalian membrane two-hybrid (MaMTH), to map the PPIs between human RTKs and phosphatases. The resulting RTK-phosphatase interactome reveals a considerable number of previously unidentified interactions and suggests specific roles for different phosphatase families. Additionally, the differential PPIs of some protein tyrosine phosphatases (PTPs) and their mutants suggest diverse mechanisms of these PTPs in the regulation of RTK signaling...
December 21, 2016: Molecular Cell
https://www.readbyqxmd.com/read/28064216/prevalence-of-egfr-tyrosine-kinase-domain-mutations-in-head-and-neck-squamous-cell-carcinoma-cohort-study-and-systematic-review
#20
REVIEW
Christos Perisanidis
BACKGROUND: Mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain (TKD) are associated with response and resistance to targeted therapy. The EGFR mutation status in patients with advanced oral and oropharyngeal squamous cell carcinoma (OOSCC) was evaluated. A systematic literature review was undertaken to summarize current evidence and estimate the overall prevalence of EGFR TKD mutations in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Genomic DNA was extracted from formalin-fixed, paraffin-embedded tumor samples of 113 patients with OOSCC...
January 2017: In Vivo
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