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EGFR mutations

Lei Zhu, Guotao Yin, Wei Chen, Xiaofeng Li, Xiaozhou Yu, Xiang Zhu, Wei Jiang, Chaoyang Jia, Peihe Chen, Yufan Zhang, Di Lu, Lijuan Yu, Xubin Li, Wengui Xu
BACKGROUND: The purpose of this study was to investigate an association between EGFR mutation status and 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET-CT) image features in lung adenocarcinoma. METHODS: Retrospective analysis of the data of 139 patients with lung adenocarcinoma confirmed by surgical pathology who underwent preoperative 18 F-FDG PET-CT was conducted. Correlations between EGFR mutation status, clinical characteristics, and PET-CT parameters, including the maximum standardized uptake value (SUVmax), the mean of the SUV (SUVmean), the peak of the SUV (SUVpeak) of the primary tumor, and the ratio of SUVmax between the primary tumor and the mediastinal blood pool (SUVratio), were statistically analyzed...
February 18, 2019: Thoracic Cancer
Dong Qiu, Yu Zhang, Ying-Bo Xue, Qi Shen, Hang Li, Ping Huang, Jian-Jun Hu, Yong-Sheng Wang
EGFR-activating mutations have been recognized as the most important predictor of response to EGFR-tyrosine kinase inhibitors (TKIs); however, 20-30% of patients harboring EGFR-activating mutations show poor responses. The mechanisms of such EGFR-TKI primary resistance are still poorly understood. In our case, a non-small cell lung cancer patient developed intrinsic EGFR-TKI resistance and was then confirmed to simultaneously harbor an L858R mutation and ROS1 rearrangement. Salvage chemotherapy plus Endostar showed enduring therapeutic effects, achieving a disease-free survival period of 24 months and overall survival of 30 months...
February 18, 2019: Thoracic Cancer
Tong Meng, Jiali Jin, Cong Jiang, Runzhi Huang, Huabin Yin, Dianwen Song, Liming Cheng
Objectives: Chordoma is a rare bone malignancy that affects the spine and skull base. Treatment dilemma leads to a high rate of local relapse and distant metastases. Molecular targeted therapy (MTT) is an option for advanced chordoma, but its therapeutic efficacy and safety have not been investigated systematically. Therefore, a systematic review was conducted on studies reporting MTT regimens for chordoma. Methods: Clinical trials, case series and case reports on chordoma MTT were identified using MEDLINE, Cochrane library and EMBASE, and systematically reviewed...
2019: Frontiers in Oncology
Véronique Hofman, Paul Hofman
Patients with advanced or metastatic forms of lung cancer with an activating mutation in epidermal growth factor receptor ( EGFR ) are given tyrosine kinase inhibitors (TKIs) targeted therapies that are more efficient than chemotherapy. These patients are excluded from first-line immunotherapy. After a phase of regression these tumors develop systematically resistance requiring a rapid change in therapy. At present two strategies are being discussed. The first strategy, so called "historical' sequential treatment strategy, is based on the administration of first- or second-generation TKIs until the emergence of therapeutic resistance and, in the case of a EGFR T790M mutation, on the administration of third-generation TKIs...
January 2019: Journal of Thoracic Disease
Shruti Kate, Anuradha Chougule, Amit Joshi, Vanita Noronha, Vijay Patil, Rohit Dusane, Leena Solanki, Priyanka Tiwrekar, Vaishakhi Trivedi, Kumar Prabhash
Background: The significance of uncommon EGFR mutations in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients is incompletely known. We aimed to analyze the demographic profile, outcome, and treatment attributes of these patients. Patients and methods: We retrospectively surveyed 5,738 advanced NSCLC patients who underwent EGFR testing in our center from 2013 to 2017 by in-house primer probes on real time PCR platform. Descriptive data were accumulated from electronic medical records...
2019: Lung Cancer: Targets and Therapy
Taiki Hakozaki, Makiko Yomota
Background: Osimertinib is the standard of care for patients with non-small-cell lung cancer (NSCLC) patients harboring acquired EGFR T790M resistance mutation. However, the frequency of T790M resistance mutation acquisition and the efficacy of osimertinib in patients harboring uncommon EGFR mutations, which accounts for approximately 10% of EGFR mutations, remain unclear. Case presentation: We present the case of a 72-year-old Japanese woman with recurrent NSCLC harboring uncommon EGFR mutations, who was subsequently found to have acquired the T790M resistance mutation and was treated with osimertinib...
2019: OncoTargets and Therapy
Kyungmi Yang, Sang Won Jung, Hyemi Shin, Do Hoon Lim, Jung-Il Lee, Doo-Sik Kong, Ho Jun Seol, Sung Tae Kim, Do-Hyun Nam
BACKGROUND AND PURPOSE: To find genetic markers associated with response to radiotherapy (RT) in glioblastoma (GB) patients. MATERIALS AND METHODS: From Jan 2009 to Dec 2016, 161 patients with newly diagnosed IDH-wild type GB were treated with surgery and adjuvant concurrent chemoradiotherapy with the Stupp's regimen, and then genomic research proceeded with their surgical specimens. Among the 161 patients, 49 with clinically measurable disease on postoperative MRI were analyzed...
February 2019: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Xiao-Ju Wang, Rong-Jin Zhou, Ni Zhang, Zhao Jing
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become a standard therapy for non-small cell lung cancer (NSCLC) patients with sensitive mutations. However, acquired resistance inevitably emerges after a median of 6~12 months. It has been demonstrated that autophagy plays an important role in EGFR-TKI resistance. 20(S)-ginsenoside Rg3 (Rg3) is proposed to sensitize the cancer cells to chemotherapy by inhibiting autophagy. We examined the ability of Rg3 to inhibit autophagy and increase the sensitivity of NSCLC cells to icotinib...
February 14, 2019: European Journal of Pharmacology
Farrukh Aqil, Radha Munagala, Jeyaprakash Jeyabalan, Ashish K Agrawal, Al-Hassan Kyakulaga, Sarah A Wilcher, Ramesh C Gupta
Gene-silencing with targeted siRNAs has great potential as a therapeutic approach for various diseases including cancer. However, intracellular delivery of siRNA is challenging. We used bovine milk exosomes as a novel system for siRNA delivery. First, we demonstrated that exosomes can deliver endogenous RNA payloads into recipient cells. Next, we loaded siRNA against specific genes including VEGF, EGFR, AKT, MAPK, and KRAS. We utilized 5'-32 P-labeled siKRAS as a tracer and found exosome loading with siRNA could be variable...
February 13, 2019: Cancer Letters
Paolo Borghetti, Marco Lorenzo Bonù, Rachele Giubbolini, Niccolo' Giaj Levra, Rosario Mazzola, Marco Perna, Luca Visani, Fiammetta Meacci, Maria Taraborrelli, Luca Triggiani, Davide Franceschini, Carlo Greco, Alessio Bruni, Stefano Maria Magrini, Vieri Scotti
PURPOSE: To investigate the role of radiotherapy (RT) in the management of EGFR- or ALK-mutated metastatic non-small cell lung cancer (NSCLC) treated with TKI. MATERIALS AND METHODS: Clinical data of 106 patients (pts) from five Institutions treated with RT concomitant to TKI were retrospectively revised. Overall survival (OS) and toxicities were analyzed as endpoints of the study. RESULTS: Median age of pts was 65 years. TKIs were given for EGFR (81%)- or ALK (19%)-mutated metastatic NSCLC...
February 15, 2019: La Radiologia Medica
Arrvind Raghunath, Kunal Desai, Manmeet S Ahluwalia
In the past, the standard of care for treatment of BM was whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgery. There has been a greater role for medical therapies in the last two decades due to the discovery of driver mutations and corresponding targeted therapies. These innovations have dramatically altered the approach to treating these patients. Some of the important mutations include epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in small cell lung cancer, human epidermal growth factor receptor (HER2) mutation in breast cancer, and BRAF mutation in melanoma...
February 15, 2019: Current Treatment Options in Oncology
Yalei Yin, Mingju Sun, Xi Zhan, Changqing Wu, Pengyu Geng, Xiaoyan Sun, Yunsong Wu, Shuijun Zhang, Jianhua Qin, Zhengping Zhuang, Yang Liu
BACKGROUND: The bromodomain and extra-terminal domain (BET) inhibitor is a type of anti-tumor agent, currently being evaluated in phase I and II clinical trials for cancer therapy. It can decrease MYC expression levels and cause effective anti-tumor effects in diverse human cancers. However, its cytotoxic effect and related mechanisms of drug resistance are poorly understood in hepatocellular carcinomas (HCC). Here, we investigated the anti-tumor effects of BET inhibitor on HCC and the molecular mechanisms involved in its associated drug resistance...
February 15, 2019: Journal of Experimental & Clinical Cancer Research: CR
Yuchen Bai, Xiaoxia Chen, Likun Hou, Jun Qian, Tao Jiang, Caicun Zhou, Maciej Ciebiada
Objective: Epidermal growth factor receptor (EGFR) activation was reported to upregulate programmed death-ligand 1 (PD-L1) expression in lung cancer cells and subsequently contribute to immune escape, indicating its critical role in EGFR-driven lung tumors. This study characterized PD-L1 expression in patients with surgically resected EGFR-mutant non-small cell lung cancer (NSCLC). The effect of PD-L1 expression on clinical outcomes was also investigated in advanced EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors (TKIs)...
November 2018: Cancer Biology & Medicine
Kana Ohashi, Mikio Takamori, Yukiko Takahashi, Shoko Kawai, Miake Yamamoto, Miyako Kitazono, Kengo Murata, Akihiko Wada
Epidermalgrowth factor receptor tyrosine kinase inhibitor(EGFR-TKI)is the first choice for the treatment of EGFR mutation- positive advanced non-small cell lung cancer(NSCLC). There have been few reports on the efficacy and safety of gefitinib in elderly patients with EGFR mutation-positive advanced NSCLC. We retrospectively assessed the efficacy and safety of gefitinib as first-line chemotherapy in 22 patients with advanced NSCLC aged 75 years or older and who were treated with gefitinib. The response rate was 81...
January 2019: Gan to Kagaku Ryoho. Cancer & Chemotherapy
James Chih-Hsin Yang, Frances A Shepherd, Dong-Wan Kim, Gyeong-Won Lee, Jong Seok Lee, Gee-Chen Chang, Sung Sook Lee, Yu-Feng Wei, Yun Gyoo Lee, Gianluca Laus, Barbara Collins, Francesca Pisetzky, Leora Horn
INTRODUCTION: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Durvalumab is an anti-PD-L1 monoclonal antibody. The Phase III open-label CAURAL trial (NCT02454933) investigated osimertinib plus durvalumab versus osimertinib monotherapy in patients with EGFR-TKI sensitizing and T790M mutation-positive advanced non-small cell lung cancer (NSCLC) and disease progression following EGFR-TKI therapy. METHODS: Patients were randomly assigned 1:1 to receive oral osimertinib (80 mg once daily) with/without durvalumab (10 mg/kg intravenously every two weeks), until progression...
February 11, 2019: Journal of Thoracic Oncology
Li Tan, Yinying Wu, Xiaowei Ma, Yanli Yan, Shuai Shao, Jiaxin Liu, Hailin Ma, Rui Liu, Linyan Chai, Juan Ren
Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have different clinicopathological characteristics compared with EGFR wild type NSCLC. A growing number of studies focused on the relevance between EGFR mutation status and brain metastases (BM) in NSCLC, but it remains controversial. Therefore, this study performed a comprehensive meta-analysis to untangle this issue. Several electronic databases including Pubmed, Embase, Web of science and Cochrane database were thoroughly searched...
February 14, 2019: Pathology Oncology Research: POR
Marcela Nunes Rosa, Adriane Feijó Evangelista, Letícia Ferro Leal, Cristina Mendes De Oliveira, Viviane Aline Oliveira Silva, Carla Carolina Munari, Fernanda Franco Munari, Graziela De Macêdo Matsushita, Ricardo Dos Reis, Carlos Eduardo Andrade, Cristiano de Pádua Souza, Rui Manuel Reis
Cervical cancer is the fourth most common cancer in women. Although cure rates are high for early stage disease, clinical outcomes for advanced, metastatic, or recurrent disease remain poor. To change this panorama, a deeper understanding of cervical cancer biology and novel study models are needed. Immortalized human cancer cell lines such as HeLa constitute crucial scientific tools, but there are few other cervical cancer cell lines available, limiting our understanding of a disease known for its molecular heterogeneity...
February 13, 2019: Scientific Reports
Yujie Dong, Zhen Zhou, Jianguo Wang, Li Ma, Zichen Liu, Yuxuan Wang, Jing Song, Shucai Zhang, Nanying Che
OBJECTIVE: Recently, a low frequency of de novo T790M mutations existing in tumor tissues before TKIs therapy has been reported. However, the origin of T790M and its impact on clinical outcomes is still being debated. This study aimed to use highly sensitive methods to detect T790M before and after TKIs therapy and investigated the correlation of T790M with clinical prognosis. PATIENTS AND METHODS: Matched tumor samples before and after treatment were collected from 61 lung adenocarcinoma (LAC) patients in Beijing Chest Hospital between June 2014 to October 2017...
January 30, 2019: Pathology, Research and Practice
Wen-Ya Li, Ting-Ting Zhao, Hui-Mian Xu, Zhen-Ning Wang, Ying-Ying Xu, Yunan Han, Yong-Xi Song, Jian-Hua Wu, Hao Xu, Song-Cheng Yin, Xing-Yu Liu, Zhi-Feng Miao
BACKGROUND: The brain is a common site for metastasis in non-small-cell lung cancer (NSCLC). This study was designed to evaluate the relationship between the mutational of the epidermal growth factor receptor (EGFR) and overall survival (OS) in NSCLC patients with brain metastases. METHODS: Searches were performed in PubMed, EmBase, and the Cochrane Library to identify studies evaluating the association of EGFR mutation with OS in NSCLC patients through September 2017...
February 13, 2019: BMC Cancer
Agnes McAuliffe, Poorva Bindal, Meredith Haley, James Vredenburgh
Non-small cell lung adenocarcinoma is the most common type of lung cancer but is often difficult to treat. New treatment options have emerged with the class of tyrosine kinase inhibitors, but it has been found that certain genetic mutations in the epidermal growth factor receptor (EGFR) receptor are not as sensitive to this treatment as others. We present a case of a 78-year-old man who was diagnosed with stage IV non-small cell lung adenocarcinoma with an EGFR exon 20 mutations treated with pemetrexed, nivolumab, and then docetaxel...
February 13, 2019: Journal of Oncology Pharmacy Practice
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