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Targeted therapy lung cancer

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https://www.readbyqxmd.com/read/28230005/current-mechanism-of-acquired-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-and-updated-therapy-strategies-in-human-nonsmall-cell-lung-cancer
#1
REVIEW
Kaixian Zhang, Qianqian Yuan
Lung cancer continues to be a major health problem and the most common cancer-related mortality worldwide with about 80%-85% patients suffering from nonsmall cell lung cancer (NSCLC). More than 80% of NSCLC cases are often diagnosed as advanced stage and harbor epidermal growth factor receptor (EGFR) activating mutation. Although great success in initial response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are found in EGFR-mutant NSCLC patients, acquired resistance usually occurs on the continuous treatment...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28228226/-progress-of-pd-1-pd-l1-inhibitors-in-non-small-cell-lung-cancer
#2
Zhansheng Jiang, Zhanyu Pan, Xiubao Ren
Pembrolizumab, an inhibitor target programmed death 1 (PD-1), was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC). It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1) inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR) was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS) with single pembrolizumab in first line was nearly 1 year (10...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28228224/-clinical-advanced-in-early-stage-alk-positive-non-small-cell-lung-cancer-patients
#3
Qiongqiong Gao, Xiangli Jiang, Chun Huang
Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28225782/chronic-treatment-of-non-small-cell-lung-cancer-cells-with-gefitinib-leads-to-an-epigenetic-loss-of-epithelial-properties-associated-with-reductions-in-microrna-155-and-200c
#4
Michiko Narita, Eri Shimura, Atsumi Nagasawa, Toshiki Aiuchi, Yukari Suda, Yusuke Hamada, Daigo Ikegami, Chizuru Iwasawa, Kazuhiko Arakawa, Katsuhide Igarashi, Naoko Kuzumaki, Yusuke Yoshioka, Takahiro Ochiya, Hideyuki Takeshima, Toshikazu Ushijima, Minoru Narita
BACKGROUND: The EGFR tyrosine kinase inhibitor gefitinib is used in therapy for non-small-cell lung cancer (NSCLC). However, its application is limited by resistance-accelerated disease progression, which is accompanied by the epithelial-to-mesenchymal transition (EMT). In the present study, we performed multiple expression analyses of microRNAs (miRNAs) and quantified the expression of several related EMT players in gefitinib-resistant NSCLC cells. METHODS AND RESULTS: To establish gefitinib-resistant NSCLC cells, gefitinib-sensitive HCC827 cells, which exhibit an in-frame deletion [E746-A750] in EGFR exon 19, were exposed to gefitinib for at least 1...
2017: PloS One
https://www.readbyqxmd.com/read/28225753/complement-drives-glucosylceramide-accumulation-and-tissue-inflammation-in-gaucher-disease
#5
Manoj K Pandey, Thomas A Burrow, Reena Rani, Lisa J Martin, David Witte, Kenneth D Setchell, Mary A Mckay, Albert F Magnusen, Wujuan Zhang, Benjamin Liou, Jörg Köhl, Gregory A Grabowski
Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28225269/indazole-based-covalent-inhibitors-to-target-drug-resistant-epidermal-growth-factor-receptor
#6
Stefano Tomassi, Jonas Lategahn, Julian Engel, Marina Keul, Hannah Lea Tumbrink, Julia Ketzer, Thomas Mühlenberg, Matthias Baumann, Carsten Schultz-Fademrecht, Sebastian Bauer, Daniel Rauh
The specific targeting of oncogenic mutant epidermal growth factor receptor (EGFR) is a breakthrough in targeted cancer therapy and marks a drastic change in the treatment of non-small cell lung cancer (NSCLC). The recurrent emergence of resistance to these targeted drugs requires the development of novel chemical entities that efficiently inhibit drug-resistant EGFR. Herein, we report the optimization process for a hit compound that has emerged from a phenotypic screen resulting in indazole-based compounds...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28224401/synchronous-bilateral-breast-cancer-irradiation-clinical-and-dosimetrical-issues-using-volumetric-modulated-arc-therapy-and-simultaneous-integrated-boost
#7
Alba Fiorentino, Rosario Mazzola, Stefania Naccarato, Niccolò Giaj-Levra, Sergio Fersino, Gianluisa Sicignano, Umberto Tebano, Francesco Ricchetti, Ruggero Ruggieri, Filippo Alongi
OBJECTIVES: The aim of the present retrospective analysis was to evaluate dosimetric parameters, feasibility and outcome for Synchronous Bilateral Breast Cancer (SBBC) patients treated with adjuvant radiotherapy (RT) by Volumetric Modulated Arc Therapy (VMAT). METHODS: From September 2011 to April 2016, 1100 Breast Cancer (BC) patients were referred to our institution to receive adjuvant breast RT, and those with SBBC were selected for the present analysis. A total of 16 patients were identified...
February 21, 2017: La Radiologia Medica
https://www.readbyqxmd.com/read/28223542/the-in-vitro-and-vivo-effects-of-nuclear-and-cytosolic-parafibromin-expression-on-the-aggressive-phenotypes-of-colorectal-cancer-cells-a-search-of-potential-gene-therapy-target
#8
Hua-Chuan Zheng, Jia-Jie Liu, Jing Li, Ji-Cheng Wu, Lei Yang, Gui-Feng Zhao, Xin Zhao, Hua-Mao Jiang, Ke-Qiang Huang, Zhi-Jie Li
Down-regulated parafibromin is positively linked to the pathogenesis of parathyroid, lung, breast, ovarian, gastric and colorectal cancers. Here, we found that wild-type (WT) parafibromin overexpression suppressed proliferation, tumor growth, induced cell cycle arrest and apoptosis in colorectal cancer cells (p<0.05), but it was the converse for mutant-type (MT, mutation in nucleus localization sequence) parafibromin (p<0.05). Both WT and MT transfectants inhibited migration and invasion, and caused better differentiation (p<0...
February 16, 2017: Oncotarget
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
#9
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...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223427/calcium-dependent-enhancement-by-extracellular-acidity-of-the-cytotoxicity-of-mitochondrial-inhibitors-against-melanoma
#10
Fumihito Noguchi, Shigeki Inui, Clare Fedele, Mark Shackleton, Satoshi Itami
Extracellular acidity is a hallmark of cancers and is independent of hypoxia. Since acidity potentiates malignant phenotypes, therapeutic strategies that enhance the targeting of oncogenic mechanisms in an acidic microenvironment should be effective. We report here that drugs which abrogate mitochondrial respiration show enhanced cytotoxicity against melanoma cells in a normoxic but acidic extracellular pH, independent from P53 mutations, BRAF (V600E) mutations and/or resistance against BRAF inhibitors. Conversely, the cytotoxicity against melanoma cells of mitochondrial inhibitors is impaired by a neutral or alkaline extracellular pH and in vivo systemic alkalinization with NaHCO3 enhanced subcutaneous tumor growth and lung metastasis of B16F10 cells in mice treated with the mitochondrial inhibitor phenformin...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28220783/an-integrative-approach-unveils-fosl1-as-an-oncogene-vulnerability-in-kras-driven-lung-and-pancreatic-cancer
#11
Adrian Vallejo, Naiara Perurena, Elisabet Guruceaga, Pawel K Mazur, Susana Martinez-Canarias, Carolina Zandueta, Karmele Valencia, Andrea Arricibita, Dana Gwinn, Leanne C Sayles, Chen-Hua Chuang, Laura Guembe, Peter Bailey, David K Chang, Andrew Biankin, Mariano Ponz-Sarvise, Jesper B Andersen, Purvesh Khatri, Aline Bozec, E Alejandro Sweet-Cordero, Julien Sage, Fernando Lecanda, Silve Vicent
KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identifies mutant KRAS lung and pancreatic cancer patients with the worst survival outcome...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28220630/clinical-value-of-the-new-international-association-for-the-study-of-lung-cancer-american-thoracic-society-european-respiratory-society-classification-of-lung-adenocarcinoma
#12
Ziwei Guo, Fumei Yi, Wencheng Yin, Yu Zhang, Qian Li, Yangchun Gu, Yu Xiao, Baoshan Cao, Liwen Ma, Li Liang
BACKGROUND: We explored correlations between the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, epidermal growth factor receptor (EGFR) mutation status, and prognosis. METHODS: Data from 293 patients with lung adenocarcinoma were classified according to the new classification. Fisher's exact, χ(2) , and log-rank tests and Cox regression analysis were used to analyze correlations between EGFR mutation status, lung cancer prognosis, and the new histologic subtype...
February 21, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28219480/de-repression-of-the-rac-activator-elmo1-in-cancer-stem-cells-drives-progression-of-tgf%C3%AE-deficient-squamous-cell-carcinoma-from-transition-zones
#13
Heather A McCauley, Véronique Chevrier, Daniel Birnbaum, Géraldine Guasch
Squamous cell carcinomas occurring at transition zones are highly malignant tumors with poor prognosis. The identity of the cell population and the signaling pathways involved in the progression of transition zone squamous cell carcinoma are poorly understood, hence representing limited options for targeted therapies. Here, we identify a highly tumorigenic cancer stem cell population in a mouse model of transitional epithelial carcinoma and uncover a novel mechanism by which loss of TGFβ receptor II (Tgfbr2) mediates invasion and metastasis through de-repression of ELMO1, a RAC-activating guanine exchange factor, specifically in cancer stem cells of transition zone tumors...
February 21, 2017: ELife
https://www.readbyqxmd.com/read/28219202/-precision-treatment-after-resistance-to-first-generation-egfr-tki-in-patients-with-non-small-cell-lung-cancer
#14
C Pi, Y C Zhang, C R Xu, Q Zhou
Recently, with the research progress in molecular classification, the treatment of advanced non-small cell lung cancer (NSCLC) has been established as a model of anti-tumor treatment of precision medicine. The discovery of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has transformed the treatment of NSCLC from platinum based doublet chemotherapy into era of target therapy. EGFR-TKI, such as erlotinib and gefitinib, have been recommended as standard first-line treatment of patients with EGFR mutation...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28219200/-application-strategies-of-the-third-generation-egfr-tki-in-the-context-of-precision-medicine
#15
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/28219199/-improving-the-internal-medical-care-to-set-up-a-leading-model-for-precision-medicine-development-in-lung-cancer
#16
B H Han
Lung cancer still remains the leading cause of cancer-related death worldwide. Recent development of molecular targeted therapies, especially the emergence of epidermal growth factor receptor (EGFR) inhibitors, has made an enormous progress for the treatment of non-small cell lung cancer (NSCLC). However, targeted therapy still faces many problems including acquired resistance. Several clinical trials have proved that targeted therapy can significantly improve the progression-free survival (PFS), but there are still many things needed to be improved...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28218277/mir-203-enhances-let-7-biogenesis-by-targeting-lin28b-to-suppress-tumor-growth-in-lung-cancer
#17
Yong Zhou, Hongwei Liang, Zhicong Liao, Yanbo Wang, Xiuting Hu, Xi Chen, Lin Xu, Zhibin Hu
Human cancers often exhibit increased microRNA (miRNA) biogenesis and global aberrant expression of miRNAs; thus, targeting the miRNA biogenesis pathway represents a novel strategy for cancer therapy. Here, we report that miR-203 enhances the biogenesis of tumor suppressor let-7 in lung cancer by directly targeting LIN28B. Specially, we found that the LIN28B protein levels were dramatically increased in lung cancer tissues, but its mRNA levels did not differ significantly, suggesting that a post-transcriptional mechanism is involved in LIN28B regulation...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217439/egfr-targeted-therapy-in-lung-cancer-an-evolving-story
#18
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/28216937/renal-cell-carcinoma-atypical-metastasis-to-inguinal-lymph-nodes
#19
Qamar Saeed Chaudhry, Tanweer Ahmed Naveed Bhatty, Ziauddin Khan, Elsawi Medani Osman
Renal cell carcinoma (RCC) is a common tumor of the urinary tract. It is known to have variable presentations due to the extremely vascular nature of the organ. RCC are known to metastasize to lungs, bone, and brain commonly but atypical metastasis to various sites are reported in literature but as very rare pathology. We report a case of a 60-year-old female who presented with multiple inguinal and axillary lymph node enlargements which on excision biopsy showed metastatic RCC. RCC can present with synchronous metastatic deposits in the various organs...
January 2017: Urology Annals
https://www.readbyqxmd.com/read/28216624/dual-targeted-hybrid-nanoparticles-of-synergistic-drugs-for-treating-lung-metastases-of-triple-negative-breast-cancer-in-mice
#20
Tian Zhang, Preethy Prasad, Ping Cai, Chunsheng He, Dan Shan, Andrew Michael Rauth, Xiao Yu Wu
Lung metastasis is the major cause of death in patients with triple negative breast cancer (TNBC), an aggressive subtype of breast cancer with no effective therapy at present. It has been proposed that dual-targeted therapy, ie, targeting chemotherapeutic agents to both tumor vasculature and cancer cells, may offer some advantages. The present work was aimed to develop a dual-targeted synergistic drug combination nanomedicine for the treatment of lung metastases of TNBC. Thus, Arg-Gly-Asp peptide (RGD)-conjugated, doxorubicin (DOX) and mitomycin C (MMC) co-loaded polymer-lipid hybrid nanoparticles (RGD-DMPLN) were prepared and characterized...
February 20, 2017: Acta Pharmacologica Sinica
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