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Egfr tki

Yang Chen, Youyou Wang, Lujun Zhao, Ping Wang, Jifeng Sun, Rudi Bao, Chenghai Li, Ningbo Liu
Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups...
February 2018: Cancer Biology & Medicine
Yuta Takashima, Jun Sakakibara-Konishi, Yutaka Hatanaka, Kanako C Hatanaka, Yoshihito Ohhara, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Yoshihiro Matsuno, Masaharu Nishimura
BACKGROUND: Approximately 20% to 30% of non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC...
February 19, 2018: Clinical Lung Cancer
Bo Zhang, Shuyuan Wang, Jie Qian, Wenjia Yang, Fangfei Qian, Jun Lu, Yanwei Zhang, Rong Qiao, Baohui Han
BACKGROUND: Two or more different epidermal growth factor receptor (EGFR) mutations can be detected within a single tumor sample, which represents complex mutations. However, the frequency and efficacy of tyrosine kinase inhibitor (TKI) treatments for patients harboring these mutations are unknown. METHODS: From January 2011 to January 2017, patients diagnosed with EGFR mutations were screened. The effectiveness of TKIs in patients with complex mutations was retrospectively analyzed...
March 15, 2018: Cancer
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
Xiang Cao, Yi Zhou, Hongfang Sun, Miao Xu, Xiaowen Bi, Zhihui Zhao, Binghui Shen, Fengyi Wan, Zhuan Hong, Lei Lan, Lan Luo, Zhigang Guo, Zhimin Yin
Non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations initially respond to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and have shown favorable outcomes. However, acquired drug resistance to EGFR-TKIs develops in almost all patients mainly due to the EGFR T790 M mutation. Here, we show that treatment with low-dose EGFR-TKI results in the emergence of the EGFR T790 M mutation and in the reduction of HSP70 protein levels in HCC827 cells. Erlotinib treatment inhibits HSP70 phosphorylation at tyrosine 41 and increases HSP70 ubiquitination, resulting in HSP70 degradation...
March 7, 2018: Cancer Letters
Weihua Li, Tian Qiu, Lei Guo, Yun Ling, Yibo Gao, Jianming Ying, Jie He
Primary EGFR T790M mutation is occasionally identified by routine mutation testing in tyrosine kinase inhibitor (TKI)-naive patients with non-small cell lung cancer (NSCLC). We herein aimed to compare the characteristics of primary and acquired T790M mutations in NSCLC patients, and their response to osimertinib. Using amplification refractory mutation system (ARMS) detection, primary T790M was identified in 0.5% (46/8723) of TKI-naive patients, whereas acquired T790M was detected in 49.7% (71/143) of TKI-relapsed patients...
March 7, 2018: Cancer Letters
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
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Giusy Elia, Ilaria Ruffilli, Francesca Ragusa, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages...
March 8, 2018: Oncology Reports
Yingjun Xu, Zhihui Xie, Hong Lu
Objective: This study aimed to explore the epidermal growth factor receptor (EGFR) mutation in the peripheral blood of patients with esophageal carcinoma and analyze the relationship between EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapeutic effect and EGFR mutation in peripheral blood. Methods: A retrospective analysis was performed on 66 patients with esophageal carcinoma treated with EGFR-TKI (Gefitinib) from February 2014 to March 2017 in our hospital. Real-time polymerase chain reaction was applied to detect the mutation of the EGFR gene in peripheral blood specimens before patients were treated with EGFR-TKI...
January 2018: Journal of Cancer Research and Therapeutics
Jingjing Qu, Yongchang Zhang, Xue Chen, Haiyan Yang, Chunhua Zhou, Nong Yang
Angiogenesis and its role in the growth and development of non-small cell lung cancer (NSCLC) metastases has become an increasing clinical problem. Vascular endothelial growth factor (VEGF) plays a key role in advanced NSCLC. To some extent, anti-angiogenic therapies acquired some efficacy in combination with chemotherapy, target therapy and immunotherapy. However, the reliable clinical benefit obtained with these drugs is still questionable and often quantitatively limited. In this review, the authors highlight the data obtained from first-line, second-line, epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) target therapy and immunotherapy in NSCLC patients who are treated with anti-angiogenic molecules in advanced NSCLC...
February 9, 2018: Oncotarget
Xilin Sun, Zunyu Xiao, Gongyan Chen, Zhaoguo Han, Yang Liu, Chongqing Zhang, Yingying Sun, Yan Song, Kai Wang, Fang Fang, Xiance Wang, Yanhong Lin, Lili Xu, Liming Shao, Jin Li, Zhen Cheng, Sanjiv Sam Gambhir, Baozhong Shen
Tumor heterogeneity and changes in epidermal growth factor receptor (EGFR) mutation status over time challenge the design of effective EGFR tyrosine kinase inhibitor (TKI) treatment strategies for non-small cell lung cancer (NSCLC). Therefore, there is an urgent need to develop techniques for comprehensive tumor EGFR profiling in real time, particularly in lung cancer precision medicine trials. We report a positron emission tomography (PET) tracer, N -(3-chloro-4-fluorophenyl)-7-(2-(2-(2-(2-18 F-fluoroethoxy) ethoxy) ethoxy) ethoxy)-6-methoxyquinazolin-4-amine (18 F-MPG), with high specificity to activating EGFR mutant kinase...
March 7, 2018: Science Translational Medicine
Bin Zou, Victor H F Lee, Hong Yan
BACKGROUND: Non-small cell lung cancer (NSCLC) with activating EGFR mutations, especially exon 19 deletions and the L858R point mutation, is particularly responsive to gefitinib and erlotinib. However, the sensitivity varies for less common and rare EGFR mutations. There are various explanations for the low sensitivity of EGFR exon 20 insertions and the exon 20 T790 M point mutation to gefitinib/erlotinib. However, few studies discuss, from a structural perspective, why less common mutations, like G719X and L861Q, have moderate sensitivity to gefitinib/erlotinib...
March 7, 2018: BMC Bioinformatics
Raymond Tsz-Tong Chan
Non-small cell lung cancers (NSCLC) harboring the uncommon epidermal growth factor receptor (EGFR) exon 20 insertion mutations are generally thought to be unresponsive to EGFR-tyrosine kinase inhibitor (TKI) therapy. Presented here is a case of stage IV NSCLC harboring an uncommon EGFR exon 20 insertion mutation that was maintained at minimal progressive disease for 54 months, with 36 months on the second-generation TKI afatinib. Contrary to the existing literature, the patient in this case demonstrated a long, durable response to the EGFR-TKI, which was exhibited by a long survival endpoint...
March 2018: Asia-Pacific Journal of Clinical Oncology
De-Wei Wu, Yao-Chen Wang, Lee Wang, Chih Yi Chen, Huei Lee
Purpose: MicroRNA-630 plays dual roles in apoptosis and drug resistance in human cancers. However, the role of miR-630 in resistance to tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma remains to be elucidated. Methods: Manipulation of miR-630 and its targeted gene YAP1 and/or combination of inhibitor treatments was performed to explore whether low miR-630 could confer TKI resistance due to de-targeting YAP1, and this could decrease proapoptotic protein Bad expression through the miR-630/YAP1/ERK feedback loop...
2018: Theranostics
Anna Buder, Maximilian J Hochmair, Sophia Schwab, Tatjana Bundalo, Peter Schenk, Peter Errhalt, Romana E Mikes, Gudrun Absenger, Kurt Patocka, Bernhard Baumgartner, Ulrike Setinek, Otto C Burghuber, Helmut Prosch, Robert Pirker, Martin Filipits
INTRODUCTION: Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated NSCLC who have been pre-treated with EGFR-TKIs. We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in clinical routine. METHODS: From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated NSCLC who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital PCR (ddPCR) in all patients and by tissue analyses in selected patients...
March 2, 2018: Journal of Thoracic Oncology
Bo Zhang, Jianlin Xu, Xueyan Zhang, Ping Gu, Huimin Wang, Shuyuan Wang, Jie Qian, Rong Qiao, Yanwei Zhang, Wenjia Yang, Fangfei Qian, Yan Zhou, Jun Lu, Lele Zhang, Baohui Han
OBJECTIVES: Occasionally, primary 20 T790M/insertion plus sensitive mutations can be detected within a single tumor sample by routine molecular testing, but the optimal clinical management for these patients is unclear. Herein, we determined the optimal treatment strategy for these patients. MATERIALS AND METHODS: From January 2011 to January 2017, patients diagnosed with epidermal growth factor receptor (EGFR) mutation were screened. For these harboring primary 20 T790M/insertion plus sensitive mutations, the effectiveness of the first or third generation tyrosine kinase inhibitors (TKIs) were retrospectively analyzed...
March 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Juan Chen, Jie-da Cui, Xiao-Tong Guo, Xia Cao, Qing Li
Epidermal growth receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs) have emerged as first-line drugs for advanced non-small-cell lung cancer (NSCLC) patients with EFGR mutations. However, most patients with NSCLC show acquired resistance to EGFR-TKIs, and low expression of NF1 is a mechanism of EGFR-TKI resistance in lung cancer. However, the mechanism by which NF1 is downregulated in EGFR-TKI-resistant NSCLC is unclear. Here, we found the increased expression of miR-641 in NSCLC cells and human NSCLC samples with resistance to TKI compared to those with sensitive to TKI...
March 1, 2018: Cancer Medicine
Romain Corre, Radj Gervais, Florian Guisier, Louis Tassy, Florent Vinas, Régine Lamy, Gislaine Fraboulet, Laurent Greillier, Helene Doubre, Renaud Descourt, Christos Chouaid, Jean-Bernard Auliac
Objective: To assess efficacy and tolerance of EGFR tyrosine-kinase inhibitors (TKIs) for advanced EGFR-mutated non-small cell lung cancer (NSCLC) in octogenarians. Patients and methods: Patients aged 80 years or older with EGFR-mutated NSCLC treated by EGFR TKI between January 2011 and March 2015 whatever the line of treatment were retrospectively selected. Results: 20 centers retrospectively included 114 patients (women, 77.2%; Caucasians, 98...
February 2, 2018: Oncotarget
Shingo Nasu, Hidekazu Suzuki, Takayuki Shiroyama, Ayako Tanaka, Kaori Iwata, Noriko Ryota, Yuki Ueda, S O Takata, Kentaro Masuhiro, Satomu Morita, Naoko Morishita, Norio Okamoto, Tomonori Hirashima
BACKGROUND/AIM: Although afatinib has a strong efficacy, it can be toxic; hence, we aimed to determine markers of response to afatinib in order to assess prognosis. PATIENTS AND METHODS: Information on clinical background, therapeutic effects, and adverse events was collected retrospectively at one Institution from patients treated with afatinib as initial epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). We examined the relationship between different adverse events and their effects on prognosis...
March 2018: Anticancer Research
Ping Zhang, Xin Nie, Zhixin Bie, Lin Li
Smoking is a risk factor for nonsmall cell lung carcinoma (NSCLC) and is associated with a lower response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI). The purpose of this study is to examine the impact of the smoking status on the benefits from first-line EGFR-TKI in NSCLC patients with EGFR mutation.This was a retrospective study of 159 patients with advanced NSCLC treated at the Beijing Hospital between January 2011 and December 2016. The follow-up was censored on December 2017...
March 2018: Medicine (Baltimore)
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