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https://www.readbyqxmd.com/read/29143497/detection-and-monitoring-of-driver-mutations-by-next-generation-sequencing-in-squamous-cell-lung-cancer-patient-and-possible-predictive-biomarker-of-third-generation-egfr-tyrosine-kinase-inhibitors
#1
Xiaoyan Shen, Jie Shen, Hang Zhang, Yuxin Cheng, Yang Yang, Jiahui Gao, Yu Zhang, Rutian Li, Baorui Liu, Lifeng Wang
Driver mutation detection and the development of targeted drugs have significantly improved survival of advanced lung adenocarcinoma patients with driver mutations. However, we still lack understanding of druggable mutations in patients with advanced squamous cell lung cancer (SQCLC). Less than 10% of SQCLC patients have EGFR gene mutations, thus we have limited knowledge of biological molecular changes with first generation EGFR-tyrosine kinase inhibitor (TKI) resistance. We report a case of an SQCLC patient treated with first-line platinum-doublet chemotherapy...
November 16, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29123416/frequency-and-clinical-relevance-of-egfr-mutations-and-eml4-alk-translocations-in-octogenarians-with-non-small-cell-lung-cancer
#2
Amanda Tufman, Kathrin Kahnert, Thomas Duell, Diego Kauffmann-Guerrero, Katrin Milger, Christian Schneider, Julia Stump, Zulfiya Syunyaeva, Rudolf Maria Huber, Simone Reu
Background: Tyrosine kinase inhibitors (TKIs) have improved response rates in some patients with non-small cell lung cancer (NSCLC), and testing for EGFR mutation and ALK translocation is recommended for all patients with advanced lung adenocarcinoma. The frequency of driver mutations in elderly and very elderly patients has not been described. Patients and methods: We reviewed EGFR and ALK in patients over the age of 70 years diagnosed and treated at our center in 2015 (subgroups: 70-74, 75-79 and >80 years)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29123415/impact-of-hypertrophic-pulmonary-osteoarthropathy-on-patients-with-lung-cancer
#3
Yu-Hung Fang, Chien-Chin Hsu, Meng-Jer Hsieh, Ming-Szu Hung, Ying-Huang Tsai, Yu-Ching Lin
Purpose: Hypertrophic pulmonary osteoarthropathy (HPOA) is a rare disease that most commonly occurs secondary to lung cancer. However, the clinical significance of HPOA remains unclear. The aim of this study was to evaluate the impact of HPOA on patients with lung cancer in Taiwan. Patients and methods: Data regarding lung cancer patients who demonstrated findings of HPOA on bone scintigraphy between 2010 and 2016 were retrospectively analyzed. Pathological confirmation of cases was conducted at Chiayi and Kaohsiung Chang Gang Memorial Hospital...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29121501/does-c-met-remain-a-rational-target-for-therapy-in-patients-with-egfr-tki-resistant-non-small-cell-lung-cancer
#4
REVIEW
Yi-Long Wu, Ross Andrew Soo, Giuseppe Locatelli, Uz Stammberger, Giorgio Scagliotti, Keunchil Park
Non-small cell lung cancer (NSCLC) inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. In 5-20% of cases, this can be attributed to aberrant c-Met activity, providing a clear rationale for the use of c-Met inhibitors in these patients. EGFR TKI-resistant tumors often remain sensitive to EGFR signaling, such that c-Met inhibitors are likely to be most effective when combined with continued EGFR TKI therapy. The phase III trials of the c-Met inhibitors onartuzumab and tivantinib, which failed to demonstrate significant benefit in patients with NSCLC but excluded patients with EGFR TKI-resistant disease, do not allow c-Met to be dismissed as a rational target in EGFR TKI-resistant NSCLC...
October 25, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29120087/histological-evolution-from-primary-lung-adenocarcinoma-harboring-egfr-mutation-to-high-grade-neuroendocrine-carcinoma
#5
Jikai Zhao, Jinchen Shao, Ruiying Zhao, Rong Li, Keke Yu, Lei Zhu, Jie Zhang
BACKGROUND: Although patients with EGFR mutated lung adenocarcinoma benefit greatly from tyrosine kinase inhibitors (TKIs), they inevitably develop acquired resistance after an average of 10-14 months of continuous treatment. METHODS: We retrospectively analyzed the clinical and histopathological data of eight patients with primary lung adenocarcinoma harboring EGFR mutations that transformed into high-grade neuroendocrine carcinoma after TKI therapy. Morphology scanning for neuroendocrine differentiation and immunohistochemistry for neuroendocrine markers CD56, chromogranin, and synaptophysin were performed on primary adenocarcinoma tissues and repeated biopsies...
November 9, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29119113/increased-egfr-phosphorylation-correlates-with-higher-programmed-death-ligand-1-expression-analysis-of-tki-resistant-lung-cancer-cell-lines
#6
Kenichi Suda, Leslie Rozeboom, Koh Furugaki, Hui Yu, Mary Ann C Melnick, Kim Ellison, Christopher J Rivard, Katerina Politi, Tetsuya Mitsudomi, Fred R Hirsch
Despite the recent development of immunotherapies that target programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) treatment, these therapies are less effective in NSCLC patients with epidermal growth factor receptor (EGFR) mutations. However, the molecular mechanisms underlying this lower efficacy of immunotherapies in EGFR mutant lung cancers are still unclear. In this study, we analyzed PD-L1 protein expression in lung cancer cell lines with EGFR mutations prior to and after acquisition of resistance to EGFR tyrosine kinase inhibitors (TKIs)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29118262/stress-hormones-promote-egfr-inhibitor-resistance-in-nsclc-implications-for-combinations-with-%C3%AE-blockers
#7
Monique B Nilsson, Huiying Sun, Lixia Diao, Pan Tong, Diane Liu, Lerong Li, Youhong Fan, Alissa Poteete, Seung-Oe Lim, Kathryn Howells, Vincent Haddad, Daniel Gomez, Hai Tran, Guillermo Armaiz Pena, Lecia V Sequist, James C Yang, Jing Wang, Edward S Kim, Roy Herbst, J Jack Lee, Waun Ki Hong, Ignacio Wistuba, Mien-Chie Hung, Anil K Sood, John V Heymach
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance mediated by T790M-independent mechanisms remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). We identified a targetable mechanism of EGFR inhibitor resistance whereby stress hormones activate β2-adrenergic receptors (β2-ARs) on NSCLC cells, which cooperatively signal with mutant EGFR, resulting in the inactivation of the tumor suppressor, liver kinase B1 (LKB1), and subsequently induce interleukin-6 (IL-6) expression...
November 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29111173/epidermal-growth-factor-receptor-mutation-predicts-favorable-outcomes-in-non-small-cell-lung-cancer-patients-with-brain-metastases-treated-with-stereotactic-radiosurgery
#8
Wen-Chi Yang, Furen Xiao, Jin-Yuan Shih, Chao-Chi Ho, Ya-Fang Chen, Ham-Min Tseng, Kuan-Yu Chen, Wei-Yu Liao, Chong-Jen Yu, James Chih-Hsin Yang, Sung-Hsin Kuo, Jason Chia-Hsien Cheng, Pan-Chyr Yang, Feng-Ming Hsu
PURPOSE: The impact of epidermal growth factor receptor (EGFR) mutations on radiotherapy for brain metastases (BM) is undetermined. We evaluated the effects of EGFR mutation status on responses and outcomes in non-small cell lung cancer (NSCLC) patients with BM, treated with upfront or salvage stereotactic radiosurgery (SRS). METHODS AND MATERIALS: From 2008 to 2015, 147 eligible NSCLC patients with 300 lesions were retrospectively analyzed. Patterns of tyrosine kinase inhibitor (TKI) therapy were recorded...
October 27, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29110841/heterogeneous-resistance-mechanisms-in-an-egfr-exon-19-mutated-non-small-cell-lung-cancer-patient-treated-with-erlotinib-persistent-fgfr3-mutation-localized-transformation-to-egfr-mutated-sclc-and-acquired-t790m-egfr-mutation
#9
Eric Santoni-Rugiu, Morten Grauslund, Linea C Melchior, Junia C Costa, Jens B Sørensen, Edyta M Urbanska
Patients with epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer (NSCLC) obtain substantial clinical benefit from EGFR tyrosine-kinase inhibitors (TKIs), but will ultimately develop TKI-resistance resulting in median progression-free survival of 9-15 months during first-line TKI-therapy. However, type and timing of TKI-resistance cannot be predicted and several mechanisms may simultaneously/subsequently occur during TKI-treatment. In this respect, we present a 49 year-old Caucasian male ex-smoker with metastatic pulmonary adenocarcinoma (ADC) that concomitantly harbored an EGFR exon 19-mutation (p...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29110836/next-generation-sequencing-reveals-novel-resistance-mechanisms-and-molecular-heterogeneity-in-egfr-mutant-non-small-cell-lung-cancer-with-acquired-resistance-to-egfr-tkis
#10
Choong-Kun Lee, Sora Kim, Jae Seok Lee, Jeong Eun Lee, Sung-Moo Kim, In Seok Yang, Hye Ryun Kim, Jeong Ho Lee, Sangwoo Kim, Byoung Chul Cho
OBJECTIVES: Despite initial responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutant non-small cell lung cancer, patients invariably develop acquired resistance. In this study, we performed next-generation sequencing in pre- and post-EGFR-TKI tumor samples to identify novel resistance mechanisms to EGFR-TKIs. MATERIAL AND METHODS: We collected tumor tissues before EGFR-TKI treatment and after progression from 19 NSCLC patients to analyze genomic alterations in 409 cancer related genes...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29110716/postoperative-survival-of-egfr-tki-targeted-therapy-in-non-small-cell-lung-cancer-patients-with-egfr-19-or-21-mutations-a-retrospective-study
#11
Wenjing Yang, Yibo Gao, Xuelian Li, Jing Zhang, Tiejun Liu, Xiaoli Feng, Hao Pan, Xiaofan Yang, Shuanghua Xie, Xiaoshuang Feng, Zhangyan Lv, Yonggang Wang, Zhaoli Chen, Jie He
BACKGROUND: The aim of this retrospective study is to identify epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer patients and to compare the long-term postoperative outcomes in different EGFR-TKI-targeted therapy effects between the different EGFR mutation groups. METHODS: A total of 2094 postoperative non-small cell lung cancer (NSCLC) patients with EGFR gene detection were collected in the Department of Pathology in the Cancer Hospital Chinese Academy of Medical Sciences from January 2003 to January 2014...
November 6, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29108922/use-of-erlotinib-and-thalidomide-in-advanced-nsclc-patients-with-acquired-resistance-to-erlotinib-a-pilot-study
#12
Gen-He Wang, Peng-Fei Wu, Long-Hui Zhang, Ping Fang, Yong Chen, Gang Zuo, Yi-Qing Wu, Shu-Hong Wang, Guo-Ping Sun
Evidences suggested that combined blockade of the VEGF and EGFR pathways can improve the treatment efficacy of non-small-cell lung cancer (NSCLC). In our previously clinical practice, we observed that thalidomide, a potent VEGF inhibitor, can significantly decrease the tumor size of one EGFR-TKI resistance patient with lung cancer cachexia. In this pilot study, we tried to assess the efficacy and toxicity of the combination therapy of erlotinib and thalidomide in advanced NSCLC patients with acquired resistance to erlotinib...
October 18, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29108289/clinical-significance-of-cripto-1-expression-in-lung-adenocarcinoma
#13
Hua Zhang, Bin Zhang, Liuwei Gao, Lianmin Zhang, Kaikai Zhu, Runfen Cheng, Changli Wang
Cripto-1 can promote tumourigenesis and may be a potential prognostic biomarker in several malignancies, yet little is known about this protein in lung adenocarcinoma (LAC). The aim of this study was to evaluate the prognostic value of cripto-1 expression in a cohort of patients with LAC. Tumours from 290 patients with pathologically confirmed LAC were used for an immunohistochemical analysis of cripto-1 expression. The correlation between cripto-1 expression and the clinicopathological parameters of patients, EGFR-TKI sensitivity was analysed...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29104613/impact-of-exon-19-versus-exon-21-egfr-activating-mutation-on-outcomes-with-upfront-pemetrexed-carboplatin-chemotherapy
#14
Vanita Noronha, Vijay Patil, Amit Joshi, Anuradha Chougule, Atanu Bhattacharjee, Rajiv Kumar, Sucheta More, Supriya Goud, Ashay Karpe, Anant Ramaswamy, Nikhil Pande, Arun Chandrasekharan, Alok Goel, Vikas Talreja, Abhishek Mahajan, Amit Janu, Nilendu Purandare, Kumar Prabhash
Background: EGFR mutation subtype is a recognised factor impacting outcomes of patients receiving oral tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Evidence for the effect of this factor on outcomes in patients receiving pemetrexed is limited. Methods: We completed a study comparing pemetrexed-platinum combination versus oral TKI in EGFR mutation-positive patients in lung cancer. We analysed the impact of EGFR mutation subtype, specifically, exon 19 and 21 on the PFS and OS of patients treated with pemetrexed (500 mg/m(2) on day 1) and carboplatin (AUC 5 on day 1) as first-line therapy...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/29101057/cost-effectiveness-of-osimertinib-for-egfr-mutation-positive-non-small-cell-lung-cancer-after-progression-of-first-line-egfr-tki-therapy
#15
Bin Wu, Xiaohua Gu, Qiang Zhang
INTRODUCTION: To investigate the cost-effectiveness of osimertinib for the treatment of advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) T790M mutation after the failure of first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy. METHODS: A mathematical model was established by combining a decision tree and the Markov approach to project the cost-effectiveness of osimertinib for the treatment of patients who harbor an EGFR T790M mutation compared to that of standard chemotherapy, who had disease progression after first-line EGFR-TKI therapy with or without metastases to the central nervous system...
October 31, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29101033/potential-influence-of-interleukin-6-on-the-therapeutic-effect-of-gefitinib-in-patients-with-advanced-non-small-cell-lung-cancer-harbouring-egfr-mutations
#16
Tomoki Tamura, Yuka Kato, Kadoaki Ohashi, Kiichiro Ninomiya, Go Makimoto, Hiroko Gotoda, Toshio Kubo, Eiki Ichihara, Takehiro Tanaka, Koichi Ichimura, Yoshinobu Maeda, Katsuyuki Hotta, Katsuyuki Kiura
Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a key therapy used for patients with EGFR-mutant non-small cell lung cancer (NSCLC), some of whom do not respond well to its therapy. Cytokine including IL-6 secreted by tumour cells is postulated as a potential mechanism for the primary resistance or low sensitivity to EGFR-TKIs. Fifty-two patients with advanced EGFR-mutant NSCLC who had received gefitinib were assessed retrospectively. The protein expression of IL-6 in the tumour cells was assessed by immunostaining and judged as positive if ≥ 50 of 100 tumour cells stained positively...
October 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29100434/oncogenic-driver-mutations-treatment-and-egfr-tki-resistance-in-a-caucasian-population-with-non-small-cell-lung-cancer-survival-in-clinical-practice
#17
Martin Faehling, Birgit Schwenk, Sebastian Kramberg, Robert Eckert, Anna-Lena Volckmar, Albrecht Stenzinger, Jörn Sträter
Introduction: Oncogenic driver mutations activating EGFR, ALK, or BRAF in NSCLC predict sensitivity to specific tyrosine-kinase inhibitors (TKIs). We provide data on prevalence, treatment and survival of driver-mutation positive NSCLC in a predominantly Caucasian population in routine clinical practice. Patients and Methods: NSCLC patients diagnosed from 2006-2015 with an EGFR-test result were included (n=265). Testing for EGFR, ALK, or BRAF was performed if specific TKI therapy was considered...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099567/duodenal-perforation-secondary-to-erlotinib-therapy-in-a-patient-with-non-small-cell-lung-cancer
#18
Rafiullah, Wardah Sayed Shah, Navid Abdul Majid, Rezwan Islam
Lung cancer is a lethal disease with high mortality, and treatment modality varies with type of tumor and stage of the disease. Targeted molecular therapies have been developed for patients with advanced non-small cell lung cancer. The presence of epidermal growth factor receptor (EGFR) mutation qualifies the patient for EGFR-TKI (tyrosine kinase inhibitor) therapy such as erlotinib, which is not without risk. We report an interesting case of duodenal perforation secondary to erlotinib therapy. This is the second reported case of bowel perforation after erlotinib therapy in a patient with advanced non-small cell lung cancer...
February 2017: WMJ: Official Publication of the State Medical Society of Wisconsin
https://www.readbyqxmd.com/read/29097733/discovery-of-targetable-genetic-alterations-in-advanced-non-small-cell-lung-cancer-using-a-next-generation-sequencing-based-circulating-tumor-dna-assay
#19
Helei Hou, Xiaonan Yang, Jinping Zhang, Zhe Zhang, Xiaomei Xu, Xiaoping Zhang, Chuantao Zhang, Dong Liu, Weihua Yan, Na Zhou, Hongmei Zhu, Zhaoyang Qian, Zhuokun Li, Xiaochun Zhang
Next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) assays have provided a new method of identifying tumor-driving genes in patients with advanced non-small cell lung carcinoma (NSCLC), especially in those whose cancer tissues are unavailable or in those that have acquired treatment resistance. Here, we describe a total of 119 patients with advanced EGFR-TKI-naive NSCLC and 15 EGFR-TKI-resistant patients to identify somatic SNVs, small indels, CNVs and gene fusions in 508 tumor-related genes...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29092923/novel-sec61g-egfr-fusion-gene-in-pediatric-ependymomas-discovered-by-clonal-expansion-of-stem-cells-in-absence-of-exogenous-mitogens
#20
Tiziana Servidei, Daniela Meco, Valentina Muto, Alessandro Bruselles, Andrea Ciolfi, Nadia Trivieri, Matteo Lucchini, Roberta Morosetti, Massimiliano Mirabella, Maurizio Martini, Massimo Caldarelli, Anna Lasorella, Marco Tartaglia, Riccardo Riccardi
The basis for molecular and cellular heterogeneity in ependymomas of the central nervous system is not understood. This study suggests a basis for this phenomenon in the selection for mitogen-independent (MI) stem-like cells with impaired proliferation but increased intracranial tumorigenicity. MI ependymoma cell lines created by selection for EGF/FGF2-independent proliferation exhibited constitutive activation of EGFR, AKT, and STAT3 and sensitization to the antiproliferative effects of EGFR tyrosine kinase inhibitors (TKI)...
November 1, 2017: Cancer Research
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