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https://www.readbyqxmd.com/read/28448787/relationship-between-her2-and-jak-stat-socs3-signaling-pathway-and-clinicopathological-features-and-prognosis-of-ovarian-cancer
#1
An-Quan Shang, Jian Wu, Feng Bi, Yu-Jie Zhang, Lei-Rong Xu, Ling-Ling Li, Fei-Fei Chen, Wei-Wei Wang, Jian-Jun Zhu, You-Yi Liu
OBJECTIVE: The study aims to explore the relationship between expressions of HER2 and JAK/STAT3-SOCS3 signaling pathway and clinicopathological features and prognosis of ovarian cancer (OC). METHODS: A total of 136 OC patients were collected. Immunohistochemistry was applied to measure the expressions of STAT3, p-STAT3, SOCS3, HER2 and p-HER2 in the tumor tissues and adjacent normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expressions of HER2, SOCS3 and STAT3 and western blotting was applied for protein expressions of HER2, p-HER2, SOCS3, STAT3 and p-STAT3 in the tumor tissues and adjacent normal tissues...
April 27, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28428040/design-synthesis-and-docking-studies-of-quinazoline-analogues-bearing-aryl-semicarbazone-scaffolds-as-potent-egfr-inhibitors
#2
Yuanbiao Tu, Caolin Wang, Shan Xu, Zhou Lan, Wei Li, Jiaqian Han, Yuanzhang Zhou, Pengwu Zheng, Wufu Zhu
Two series of quinazoline derivatives bearing aryl semicarbazone scaffolds (9a-o and 10a-o) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF-7 and PC-3). The selected compound 9o was further evaluated for the inhibitory activity against EGFR kinases. Four of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 values in single-digit μM to nanomole range. Two of them are equal to more active than positive control afatinib against one or more cell lines...
April 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28426106/afatinib-versus-gefitinib-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-overall-survival-data-from-the-phase-iib-lux-lung-7-trial
#3
L Paz-Ares, E-H Tan, K O'Byrne, L Zhang, V Hirsh, M Boyer, J C-H Yang, T Mok, K H Lee, S Lu, Y Shi, D H Lee, J Laskin, D-W Kim, S A Laurie, K Kölbeck, J Fan, N Dodd, A Märten, K Park
Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R)...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28423495/afatinib-radiosensitizes-head-and-neck-squamous-cell-carcinoma-cells-by-targeting-cancer-stem-cells
#4
Muzafar A Macha, Satyanarayana Rachagani, Asif Khurshid Qazi, Rahat Jahan, Suprit Gupta, Anery Patel, Parthasarathy Seshacharyulu, Chi Lin, Sicong Li, Shuo Wang, Vivek Verma, Shosei Kishida, Michiko Kishida, Norifumi Nakamura, Toshiro Kibe, William M Lydiatt, Russell B Smith, Apar K Ganti, Dwight T Jones, Surinder K Batra, Maneesh Jain
The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416737/efficacy-of-continuous-egfr-inhibition-and-role-of-hedgehog-in-egfr-acquired-resistance-in-human-lung-cancer-cells-with-activating-mutation-of-egfr
#5
Carminia Maria Della Corte, Umberto Malapelle, Elena Vigliar, Francesco Pepe, Giancarlo Troncone, Vincenza Ciaramella, Teresa Troiani, Erika Martinelli, Valentina Belli, Fortunato Ciardiello, Floriana Morgillo
PURPOSE: The aim of this work was to investigate the efficacy of sequential treatment with first-, second- and third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and the mechanisms of acquired resistance occurring during the sequential use of these inhibitors. EXPERIMENTAL DESIGN: We developed an in vivo model of acquired resistance to EGFR-inhibitors by treating nude mice xenografted with HCC827, a human non-small-cell lung cancer (NSCLC) cell line harboring EGFR activating mutation, with a sequence of first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) (erlotinib and gefitinib), of second-generation EGFR-TKI (afatinib) plus/minus the anti-EGFR monoclonal antibody cetuximab, and of third-generation EGFR-TKI (osimertinib)...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413677/management-of-afatinib-induced-stomatitis
#6
Saeko Kato, Anna Saito, Naomi Matsuda, Hisako Suzuki, Midori Ujiie, Shinya Sato, Kunihiko Miyazaki, Takahide Kodama, Hiroaki Satoh
Severe stomatitis may lead to the need to interrupt or discontinue cancer therapy and, thus, may affect control of the primary disease. Stomatitis may also increase the risk of local and systemic infection and significantly affects the quality of life and the cost of care. The present study was conducted to evaluate the efficacy of two traditional herbal medicines in controlling treatment-induced stomatitis in a small cohort of lung cancer patients treated with afatinib. All patients who were treated with afatinib for epidermal growth factor receptor (EGFR) mutated nonsmallcell lung cancer (NSCLC) between January, 2015 and March, 2016, were included in this study...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28408617/treatment-paradigms-for-advanced-non-small-cell-lung-cancer-at-academic-medical-centers-involvement-in-clinical-trial-endpoint-design
#7
Charu Aggarwal, Hossein Borghaei
Based on the positive results of various clinical trials, treatment options for non-small cell lung cancer (NSCLC) have expanded greatly over the last 25 years. While regulatory approvals of chemotherapeutic agents for NSCLC have largely been based on improvements in overall survival, recent approvals of many targeted agents for NSCLC (afatinib, crizotinib, ceritinib, osimertinib) have been based on surrogate endpoints such as progression-free survival and objective response. As such, selection of appropriate clinical endpoints for examining the efficacy of investigational agents for NSCLC is of vital importance in clinical trial design...
April 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28393721/acquired-t790m-resistance-do-afatinib-in-egfr-mutated-lung-adenocarcinoma
#8
Kunihiko Miyazaki, Shinya Sato, Takahide Kodama, Hiroaki Satoh, Nobuyuki Hizawa
No abstract text is available yet for this article.
December 2016: Tüberküloz Ve Toraks
https://www.readbyqxmd.com/read/28391544/are-egfr-tyrosine-kinase-inhibitors-effective-in-elderly-patients-with-egfr-mutated-non-small-cell-lung-cancer
#9
REVIEW
Giandomenico Roviello, Laura Zanotti, Maria Rosa Cappelletti, Angela Gobbi, Martina Dester, Giovanni Paganini, Chiara Pacifico, Daniele Generali, Raheleh Roudi
EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib changed dramatically the history of metastatic non-small cell lung cancer (NSCLC) harbouring EGFR mutations. However, not enough data are available on the efficacy of these targeted drugs in elderly patients. The aim of this study is to analyse the available clinical data evaluating the efficacy of anti-EGFR therapies in elderly patients with advanced NSCLC carrying EGFR mutations. A literature-based meta-analysis of the results of randomized clinical trials was undertaken...
April 8, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28388009/triplet-therapy-with-afatinib-cetuximab-and-bevacizumab-induces-deep-remission-in-lung-cancer-cells-harboring-egfr-t790m-in-vivo
#10
Kenichiro Kudo, Kadoaki Ohashi, Go Makimoto, Hisao Higo, Yuka Kato, Hiroe Kayatani, Yasuko Kurata, Yoichiro Takami, Daisuke Minami, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Akiko Sato, Katsuyuki Hotta, Tadashi Yoshino, Mitsune Tanimoto, Katsuyuki Kiura
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment strategy for EGFR-mutant lung cancers; however, resistance usually occurs due to a secondary mutation, T790M, in EGFR. Combination therapy using afatinib and cetuximab has had good results in lung tumors harboring EGFR(T)(790M) mutations in clinical trials. The effect of bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, combined with EGFR-TKIs has also been investigated. We hypothesized that the dosage of afatinib and cetuximab could be reduced by combination with bevacizumab, and that the triplet therapy may result in better tumor inhibition with tolerable toxicity...
April 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28366147/-acquired-t790m-resistance-do-afatinib-in-egfr-mutated-lung-adenocarcinoma
#11
Kunihiko Miyazaki, Shinya Sato, Takahide Kodama, Hiroaki Satoh, Nobuyuki Hizawa
No abstract text is available yet for this article.
December 2016: Tüberküloz Ve Toraks
https://www.readbyqxmd.com/read/28363995/response-heterogeneity-of-egfr-and-her2-exon-20-insertions-to-covalent-egfr-and-her2-inhibitors
#12
Takayuki Kosaka, Junko Tanizaki, Raymond Paranal, Hideki Endoh, Christine Lydon, Marzia Capelletti, Claire E Repellin, Jihyun Choi, Atsuko Ogino, Antonio Calles, Dalia Ercan, Amanda Redig, Magda Bahcall, Geoffrey R Oxnard, Michael Eck, Pasi A Janne
Insertion mutations in EGFR and HER2 both occur at analogous positions in exon 20. Non-small cell lung cancer (NSCLC) patients with tumors harboring these mutations seldom achieve clinical responses to dacomitinib and afatinib, two covalent quinazoline-based inhibitors of EGFR or HER2, respectively. In this study, we investigated the effects of specific EGFR and HER2 exon 20 insertion mutations from NSCLC patients that had clinically achieved a partial response after dacomitinib treatment. We identified Gly770 as a common feature among the drug-sensitive mutations...
March 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28360035/prognostic-value-of-early-response-assessment-using-18f-fdg-pet-in-patients-with-advanced-non-small-cell-lung-cancer-treated-with-tyrosine-kinase-inhibitors
#13
Jun Ma, Xiaojing Wu, Jianghong Li, Zhihua Wang, Yi Wang
The purpose of this meta-analysis was to determine the prognostic value of early response assessment using (18F)fluorodeoxyglucose (FDG)-positron emission thermography (PET) in patients with advanced non-small cell lung cancer (NSCLC) treated with tyrosine-kinase inhibitors (TKIs). MEDLINE, PubMed, Cochrane, EMBASE, and Google Scholar databases were searched until August 1, 2016 using the keywords non-small cell lung carcinoma, positron-emission tomography, fluorodeoxyglucose, prognosis, disease progression, survival, erlotinib, gefitinib, and afatinib...
March 30, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28359250/insight-into-discovery-of-next-generation-reversible-tmlr-inhibitors-targeting-egfr-activating-and-drug-resistant-t790m-mutants
#14
Subhash Mohan Agarwal, Divyani Pal, Mansi Gupta, Ravi Saini
Cancer is one of the most challenging diseases among the various causes of deaths worldwide. Among cancer, lung cancer rules as the leading cause of cancer-related deaths annually.The majority of the lung cancers identified are non-small cell lung cancer (NSCLC). Clinically, the Epidermal Growth Factor Receptor (EGFR) is a therapeutically accepted target for NSCLC. Many therapeutic leads that target this transmembrane receptor protein were tested for anti-EGFR activity that led to the discovery of gefitinib and erlotinib...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28356747/second-line-afatinib-administration-in-an-elderly-patient-with-squamous-cell-carcinoma
#15
Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Michael Steinheimer, Naim Benhassen, Chrysanthi Sardeli, Nikos Stalikas, Melpomeni Toitou, Haidong Huang
INTRODUCTION: The majority of cases of lung cancer are still diagnosed at a late stage. At this stage, palliative therapeutic options including nonspecific cytotoxic drugs, targeted therapy, or immunotherapy can be utilized. In 2016, immunotherapy was approved in Europe for squamous cell carcinoma and adenocarcinoma. Moreover, afatinib was also approved as second-line therapy for squamous cell carcinoma. CASE REPORT: This article presents a case of a 76-year-old male with squamous cell carcinoma who received nab-paclitaxel as first-line therapy, and his treatment was switched to the tyrosine kinase inhibitor afatinib (40 mg) after disease progression with left lung atelectasis...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28344665/treatment-choice-in-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-carcinoma-latest-evidence-and-clinical-implications
#16
REVIEW
Oscar Juan, Sanjay Popat
Discovery of sensitizing mutations in epidermal growth factor receptor (EGFR) and the subsequent development of EGFR tyrosine kinase inhibitors (TKIs) have substantially changed the treatment of lung cancer. First-line treatment with EGFR TKIs (gefitinib, erlotinib and afatinib) has demonstrated a superior response rate and progression-free survival (PFS) compared with chemotherapy in EGFR-mutation positive patients. However, a number of open questions remain, such as choice between the three EGFR TKIs licensed, treatment of patients unsuitable for chemotherapy due to morbidity or advanced age, management of acquired resistance and optimal biological sample to determine EGFR status...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28337371/combinational-therapy-of-crizotinib-and-afatinib-for-malignant-pleural-mesothelioma
#17
Liyan Huang, Muyan Cai, Xu Zhang, Fang Wang, Likun Chen, Meng Xu, Ke Yang, Zhen Chen, Xiaokun Wang, Liwu Fu
Malignant pleural mesothelioma (MPM) is a relative rare but highly aggressive neoplasm which is associated with asbestos exposure in most patients. The majority of patients are diagnosed in advanced stages so patients neither benefit from chemotherapy (e.g. pemetrexed-platinum combination) nor from surgery. It has been reported that cellular-mesenchymal to epithelial transition factor (MET) and epidermal growth factor receptor (EGFR) were critical for MPM cell proliferation. Moreover, targeting MET and EGFR drugs have gained promising results on anti-tumor therapy...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28337370/role-of-epidermal-growth-factor-receptor-in-lung-cancer-and-targeted-therapies
#18
REVIEW
Tie-Cheng Liu, Xin Jin, Yan Wang, Ke Wang
Lung cancer is the foremost cause of cancer-related deaths world-wide. Both, the major forms of lung cancer, Non-small cell lung cancer (NSCLC) and Small cell lung cancers (SCLC), have responded effectively to chemo-, radiation and adjuvant-therapies. Tumor removal through surgery also appeared as a good therapeutic strategy. However, these therapies demonstrated unfavourable side-effects, and hence novel drugs targeting lung cancer emerged essential. Activation of epidermal growth factor receptor (EGFR)-tyrosine kinases is a key reason for lung cancer progression...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28331001/quantitative-tyrosine-phosphoproteomics-of-egfr-tyrosine-kinase-inhibitor-treated-lung-adenocarcinoma-cells-reveals-potential-novel-biomarkers-of-therapeutic-response
#19
Xu Zhang, Tapan Maity, Manoj K Kashyap, Mukesh Bansal, Abhilash Venugopalan, Sahib Singh, Shivangi Awasthi, Arivusudar Marimuthu, Harrys Kishore Charles Jacob, Natalya Belkina, Stephanie Pitts, Constance M Cultraro, Shaojian Gao, Fatos Kirkali, Romi Biswas, Raghothama Chaerkady, Andrea Califano, Akhilesh Pandey, Udayan Guha
Mutations in the Epidermal growth factor receptor (EGFR) kinase domain, such as the L858R missense mutation and deletions spanning the conserved sequence 747LREA750, are sensitive to tyrosine kinase inhibitors (TKIs). The gatekeeper site residue mutation, T790M accounts for around 60% of acquired resistance to EGFR TKIs. The first generation EGFR TKIs, erlotinib and gefitinib, and the second generation inhibitor, afatinib are FDA approved for initial treatment of EGFR mutated lung adenocarcinoma. The predominant biomarker of EGFR TKI responsiveness is the presence of EGFR TKI-sensitizing mutations...
March 22, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28325254/egfr-inhibition-in-nsclc-new-findings%C3%A2-and-opened-questions
#20
REVIEW
Francesco Passiglia, Angela Listì, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Viviana Bazan, Antonio Russo
The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients' outcomes...
April 2017: Critical Reviews in Oncology/hematology
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