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https://www.readbyqxmd.com/read/29775809/transient-asymptomatic-pulmonary-opacities-during-osimertinib-treatment-and-its-clinical-implication
#1
Hansang Lee, Ho Yun Lee, Jong-Mu Sun, Se-Hoon Lee, Youjin Kim, Song Ee Park, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
INTRODUCTION: Osimertinib is an oral, potent, irreversible 3rd generation EGFR tyrosine kinase inhibitor (TKI) approved for the treatment of T790M positive non-small cell lung cancer (NSCLC) patients who failed 1st or 2nd generation EGFR TKIs. Interstitial lung disease (ILD) is a rare complication with osimertinib, occurring in 1-3%. Recently, relatively high incidence of transient asymptomatic pulmonary opacities (TAPOs) which are different from ILD has been described. However, its clinical implication has not been fully determined yet...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29774061/immunotherapy-in-non-metastatic-non-small-cell-lung-cancer-can-the-benefits-of-stage-iv-therapy-be-translated-into-earlier-stages
#2
REVIEW
Griet Deslypere, Dorothée Gullentops, Els Wauters, Johan Vansteenkiste
Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR ) activating mutations or anaplastic lymphoma kinase ( ALK ) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29768721/real-world-study-of-regimen-containing-bevacizumab-as-first-line-therapy-in-chinese-patients-with-advanced-non-small-cell-lung-cancer
#3
Puyuan Xing, Yuxin Mu, Yan Wang, Xuezhi Hao, Yixiang Zhu, Xingsheng Hu, Hongyu Wang, Peng Liu, Lin Lin, Zhijie Wang, Junling Li
BACKGROUND: Large scale randomized controlled trials have demonstrated that the use of bevacizumab in addition to chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) conveys significant survival benefits. We explored the clinical impact of a first-line regimen containing bevacizumab (B+) versus a non-bevacizumab regimen (non-B) in advanced non-squamous NSCLC (NS-NSCLC) patients in a real world setting. METHODS: The medical records of patients with advanced NS-NSCLC who received first-line therapy with or without bevacizumab were retrospectively collected...
May 16, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29767438/serum-sp70-is-a-sensitive-predictor-of-chemotherapy-response-in-patients-with-advanced-nonsmall-cell-lung-cancer
#4
Jingping Liu, Wei Zhang, Min Gu, Yazhou Ji, Lu Yang, Xiangjun Cheng, Xuelian Xiao, Jian Xu, Chunrong Gu, Jiexin Zhang, Shichang Zhang, Dan Chen, Shiyang Pan
SP70 is a novel tumor biomarker in patients with nonsmall cell lung cancer (NSCLC). However, its role as a marker for predicting the response to chemotherapy for patients with advanced NSCLC has not been investigated. A total of 152 patients were enrolled. Serum SP70, carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and neuron-specific enolase (NSE) were detected before and after 2 cycles of chemotherapy. The correlation between serum tumor biomarker levels and chemotherapy responses and their association with epidermal growth factor receptor (EGFR) mutation status and progression-free survival (PFS) were analyzed...
May 16, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29765556/antibody-assisted-target-identification-reveals-afatinib-an-egfr-covalent-inhibitor-down-regulating-ribonucleotide-reductase
#5
Cheng-Han Yu, Chi-Chi Chou, Hsin-Fang Tu, Wei-Chieh Huang, Ya-Yeh Ho, Kay-Hooi Khoo, Ming-Shyue Lee, Geen-Dong Chang
Afatinib, used for the first-line treatment of non-small-cell lung carcinoma (NSCLC) patients with distinct epidermal growth factor receptor (EGFR) mutations, inactivates EGFR by mimicking ATP structure and forming a covalent adduct with EGFR. We developed a method to unravel potential targets of afatinib in NSCLC cells through immunoprecipitation of afatinib-labeling proteins with anti-afatinib antiserum and mass spectrometry analysis. Ribonucleotide reductase (RNR) is one of target proteins of afatinib revealed by this method...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765525/clinical-characteristics-of-non-small-cell-lung-cancer-harboring-mutations-in-exon-20-of-egfr-or-her2
#6
Masayuki Takeda, Kazuko Sakai, Hidetoshi Hayashi, Kaoru Tanaka, Junko Tanizaki, Takayuki Takahama, Koji Haratani, Kazuto Nishio, Kazuhiko Nakagawa
Unlike common epidermal growth factor receptor gene ( EGFR ) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene ( HER2 ) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exon-20 mutations of EGFR or HER2 as detected by routine application of an amplicon-based next-generation sequencing panel...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764596/-a-case-report-of-advanced-lung-adenocarcinoma-harboring-kras-mutation-treated-with-anlotinib
#7
Yudong Su, Zhaoting Meng, Xiaoyan Xu, XinYue Wang, Ran Zuo, Yunxia Hou, Kai Li, Peng Chen
In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29764594/-research-progress-of-kras-mutation-in-non-small-cell-lung-cancer
#8
Lei Liu, Suju Wei
Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all patients with lung cancer, the majority of patients with lung cancer at the time of diagnosis is in the advanced stage. The development of target therapy based on has changed the mode of treatment in patients with advanced NSCLC. In NSCLC, epidermal growth factor receptor mutation (EGFR) fusion with echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) has been shown to be a powerful biomarker...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29764589/-influence-of-different-therapies-on-egfr-mutants-by-circulating-cell-free-dna-of-lung-adenocarcinoma-and-prognosis
#9
Fei Su, Ke Zheng, Yiyun Fu, Qian Wu, Yuan Tang, Weiya Wang, Lili Jiang
BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29764507/aldolase-a-promotes-proliferation-and-g-1-s-transition-via-the-egfr-mapk-pathway-in-non-small-cell-lung-cancer
#10
Hailu Fu, Huijun Gao, Xiaoyu Qi, Lei Zhao, Donghua Wu, Yuxin Bai, Huimin Li, Xuan Liu, Jun Hu, Shujuan Shao
BACKGROUND: Our previous study demonstrated that aldolase A (ALDOA) is overexpressed in clinical human lung squamous cell carcinoma and that ALDOA promotes epithelial-mesenchymal transition and tumorigenesis. The present study aimed to explore the function of ALDOA in the modulation of non-small cell lung cancer (NSCLC) proliferation and cell cycle progression and the potential mechanism. METHODS: ALDOA was knocked down by short hairpin RNA in H520 and H1299 cells...
May 8, 2018: Cancer communications
https://www.readbyqxmd.com/read/29764505/xenograft-tumors-derived-from-malignant-pleural-effusion-of-the-patients-with-non-small-cell-lung-cancer-as-models-to-explore-drug-resistance
#11
Yunhua Xu, Feifei Zhang, Xiaoqing Pan, Guan Wang, Lei Zhu, Jie Zhang, Danyi Wen, Shun Lu
BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively...
May 9, 2018: Cancer communications
https://www.readbyqxmd.com/read/29763936/synergistic-inhibition-of-thalidomide-and-icotinib-on-human-non-small-cell-lung-carcinomas-through-erk-and-akt-signaling
#12
Xiang Sun, Yang Xu, Yi Wang, Qian Chen, Liu Liu, Yangyi Bao
BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. However, the survival of patients with EGFR-TKI administration is limited by the inevitable development of acquired drug resistance. Recently, multi-targeted drugs combination has been shown to be a promising strategy to improve the efficacy of EGFR-TKI treatment and enable the reduction of drug resistance in NSCLC...
May 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29761660/feasibility-of-re-biopsy-and-egfr-mutation-analysis-in-patients-with-non-small-cell-lung-cancer
#13
Tae-Ok Kim, In-Jae Oh, Bo Gun Kho, Ha Young Park, Jin Sun Chang, Cheol-Kyu Park, Hong-Joon Shin, Jung-Hwan Lim, Yong-Soo Kwon, Yu-Il Kim, Sung-Chul Lim, Young-Chul Kim, Yoo-Duk Choi
BACKGROUND: In cases of EGFR-tyrosine kinase inhibitor (TKI) failure, re-biopsy may be useful to understand resistance mechanisms and guide further treatment decisions. However, performing re-biopsy is challenging because of several hurdles. We assessed the feasibility of re-biopsy in advanced non-small cell lung cancer (NSCLC) patients in real-world clinical practice. METHODS: We retrospectively reviewed the clinical and pathologic data of advanced NSCLC patients who experienced disease progression after previous treatment with EGFR-TKIs at a single tertiary hospital in Korea between January 2014 and December 2016...
May 14, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29760791/serum-vegf-levels-in-the-early-diagnosis-and-severity-assessment-of-non-small-cell-lung-cancer
#14
Yanzhen Lai, Xueping Wang, Tao Zeng, Shan Xing, Shuqin Dai, Junye Wang, Shulin Chen, Xiaohui Li, Ying Xie, Yuanying Zhu, Wanli Liu
Background: Effective biomarkers are essential to the differential diagnosis and severity assessment of non-small cell lung cancer (NSCLC). This study explored the use of the serum vascular endothelial growth factor (VEGF) levels as a biomarker with the aim of achieving better management of NSCLC. Methods: Serum VEGF levels were assayed via enzyme-linked immunosorbent assay in 180 patients with NSCLC, 136 patients with benign pulmonary nodules, and 119 healthy controls. We additionally detected the serum concentration of three traditional biomarkers-carcinoembryonic antigen (CEA), cancer antigen (CA)-125, and cytokeratin 19 fragments (Cyfra 21-1)-to comparatively evaluate the efficiency and diagnostic value of VEGF in patients with NSCLC...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29758406/molecular-dynamics-guided-development-of-indole-based-dual-inhibitors-of-egfr-t790m-and-c-met
#15
Pankaj Kumar Singh, Om Silakari
Secondary acquired mutation in EGFR, i.e. EGFR T790M and amplification of c-MET form the two key components of resistant NSCLC. Thus, previously published pharmacophore models of EGFR T790M and c-MET were utilized to screen an in-house database. On the basis of fitness score, indole-pyrimidine scaffold was selected for further evaluation. Derivatives of indole-pyrimidine scaffold with variedly substituted aryl substitutions were sketched and then docked in both the targets. These docked complexes were then subjected to molecular dynamic simulations, to study the stability of the complexes and evaluate orientations of the designed molecules in the catalytic domain of the selected kinases...
April 25, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29758295/systematic-bioinformatic-approaches-reveal-novel-gene-expression-signatures-associated-with-acquired-resistance-to-egfr-targeted-therapy-in-lung-cancer
#16
Marjan Mojtabavi Naeini, Manoochehr Tavassoli, Kamran Ghaedi
OBJECTIVES: Human non-small cell lung cancer (NSCLC) that harbors activating mutations in epidermal growth factor receptor (EGFR) initially responds to treatment with EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib but eventually tumor cells acquire resistance. To date, several gene expression profiles have been reported in TKIs-resistant EGFR-mutant NSCLC. The objective of this study is to identify robust gene expression signatures, biological processes, and promising overcoming targets for TKIs-resistant EGFR-mutant NSCLC...
May 11, 2018: Gene
https://www.readbyqxmd.com/read/29755953/first-line-treatment-in-egfr-mutant-non-small-cell-lung-cancer-is-there-a-best-option
#17
REVIEW
Ajaz Bulbul, Hatim Husain
First generation or second generation EGFR tyrosine kinase inhibitors are currently the standard of care for the first-line management of non-small cell lung cancer (NSCLC) patients with activating mutations within the kinase domain of the epidermal growth factor receptor gene (1, 2). Resistance to targeted therapy can develop after 9-11 months (3-8). Third generation inhibitors were developed to target the EGFR T790M clone, which is the most common dominant second site resistance mutation after first or second generation inhibitors...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29755669/a-stitch-in-time-saves-nine-external-quality-assessment-rounds-demonstrate-improved-quality-of-biomarker-analysis-in-lung-cancer
#18
Cleo Keppens, Véronique Tack, Nils 't Hart, Lien Tembuyser, Ales Ryska, Patrick Pauwels, Karen Zwaenepoel, Ed Schuuring, Florian Cabillic, Luigi Tornillo, Arne Warth, Wilko Weichert, Elisabeth Dequeker
Biomarker analysis has become routine practice in the treatment of non-small cell lung cancer (NSCLC). To ensure high quality testing, participation to external quality assessment (EQA) schemes is essential. This article provides a longitudinal overview of the EQA performance for EGFR , ALK , and ROS1 analyses in NSCLC between 2012 and 2015. The four scheme years were organized by the European Society of Pathology according to the ISO 17043 standard. Participants were asked to analyze the provided tissue using their routine procedures...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29754184/discovery-of-a-potent-and-mutant-selective-egfr-inhibitor-that-overcomes-t790m-mediated-resistance-in-lung-cancer
#19
Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Young Hoon Sung, Woo Sung Kim, Sung-Eun Kim, Hyung Chul Ryu, Jae Sun Kim, Lu Guangying, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
BACKGROUND: Despite remarkable activity in epidermal growth factor receptor (EGFR)-mutant lung cancer patients, the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) is limited by the emergence of acquired resistance, which is mostly caused by a secondary T790M mutation. Fortunately, newly developed, mutant-selective EGFR-TKIs against T790M have been proven as an effective therapeutic approach although only osimertinib has received the FDA approval until now. OBJECTIVE: To determine the in vitro and in vivo efficacy of a new EGFR TKI, OBX1-012 in cells with mutant EGFR...
May 12, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29752127/implementation-of-next-generation-sequencing-technology-for-somatic-mutation-detection-in-routine-laboratory-practice
#20
Tindaro Giardina, Cleo Robinson, Fabienne Grieu-Iacopetta, Michael Millward, Barry Iacopetta, Dominic Spagnolo, Benhur Amanuel
The introduction of next generation sequencing (NGS) in the routine diagnostic setting is still in the development phase and has been limited by its complexity. Targeted NGS offers an attractive alternative to performing multiple single target assays and is very useful in meeting the increasing clinical demand for testing of multiple genetic aberrations in cancer specimens. To this end, we carried out a blinded validation study on 113 tumours in a diagnostic laboratory and compared mutation results from targeted NGS with those from Sanger sequencing, pyrosequencing, competitive allele specific TaqMan polymerase chain reaction (CAST PCR) and Cobas assays...
May 8, 2018: Pathology
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