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https://www.readbyqxmd.com/read/28221867/osimertinib-in-pretreated-t790m-positive-advanced-non-small-cell-lung-cancer-aura-study-phase-ii-extension-component
#1
James Chih-Hsin Yang, Myung-Ju Ahn, Dong-Wan Kim, Suresh S Ramalingam, Lecia V Sequist, Wu-Chou Su, Sang-We Kim, Joo-Hang Kim, David Planchard, Enriqueta Felip, Fiona Blackhall, Daniel Haggstrom, Kiyotaka Yoh, Silvia Novello, Kathryn Gold, Tomonori Hirashima, Chia-Chi Lin, Helen Mann, Mireille Cantarini, Serban Ghiorghiu, Pasi A Jänne
Purpose Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing ( EGFRm) and T790M resistance mutations. AURA (NCT01802632) is a phase I/II clinical trial to determine the dose, safety, and efficacy of osimertinib. This article reports the results from the phase II extension component. Patients and Methods Patients with EGFR-TKI-pretreated EGFRm- and T790M-positive advanced non-small-cell lung cancer (NSCLC) received once-daily osimertinib 80 mg...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28219203/-precision-first-line-therapy-for-advanced-non-small-cell-lung-cancer-patients-harboring-egfr-mutation
#2
D M Yuan, Y Song
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become the preferred treatment option for advanced non-small-cell lung cancer (NSCLC) patients with activating mutations in epidermal growth factor receptor (EGFR) according to major practice guidelines. Gefitinib, elortinib and icotinib formed the cornerstone of first-line EGFR-TKIs in the clinical practice in our country. Now, with the continuously emerging of new types of EGFR-TKIs and ever-increasing publication of clinical trial results on afatinib, AZD9291 and other TKIs, we have more first-line choices for patients with EGFR mutations...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28219202/-precision-treatment-after-resistance-to-first-generation-egfr-tki-in-patients-with-non-small-cell-lung-cancer
#3
C Pi, Y C Zhang, C R Xu, Q Zhou
Recently, with the research progress in molecular classification, the treatment of advanced non-small cell lung cancer (NSCLC) has been established as a model of anti-tumor treatment of precision medicine. The discovery of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has transformed the treatment of NSCLC from platinum based doublet chemotherapy into era of target therapy. EGFR-TKI, such as erlotinib and gefitinib, have been recommended as standard first-line treatment of patients with EGFR mutation...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28219201/-precision-medical-treatment-of-non-adenocarcinoma-nsclc-patients-with-egfr-mutation
#4
Z H Wang, X Y Song
EGFR tyrosine kinase inhibitors (TKIs) treatment has been established as standard therapy for EGFR-mutated adenocarcinomas. In the studies which published prospective randomized trials comparing EGFR TKIs with chemotherapy, a very low percentage of EGFR-mutated non-adenocarcinomas was enrolled in clinical trials. The efficacy of TKIs treatment for EGFR-mutated non-adenocarcinomas and their relationship with clinicopathological characteristics remain debatable. The results of retrospective studies show that the frequency of EGFR mutation is lower in non-adenocarcinoma than that of adenocarcinoma and efficacy of TKIs treatment for non-adenocarcinoma is inferior to adenocarcinoma...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28219200/-application-strategies-of-the-third-generation-egfr-tki-in-the-context-of-precision-medicine
#5
J Zhao, S J Zhang, C C Zhou
With the advances in molecular detection technology and the emergence of various targeted agents, we have entered the era of precision medicine across the whole process of cancer diagnosis and treatment. Tyrosine kinase inhibitors targeting epidermal growth factor receptor gene mutation, the most common driver, have been developed from the first generation to the third generation, improving the survival and life quality of patients with advanced non-small cell lung cancer. It is critically important how to rank these targeted agents and arrange combination therapies, and this review will focus on the strategies of the third-generation EGFR-TKI in the context of precision medicine...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28219002/molecular-testing-for-gastrointestinal-cancer
#6
Hye Seung Lee, Woo Ho Kim, Yoonjin Kwak, Jiwon Koh, Jeong Mo Bae, Kyoung-Mee Kim, Mee Soo Chang, Hye Seung Han, Joon Mee Kim, Hwal Woong Kim, Hee Kyung Chang, Young Hee Choi, Ji Y Park, Mi Jin Gu, Min Jin Lhee, Jung Yeon Kim, Hee Sung Kim, Mee-Yon Cho
With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wild-type RAS (KRAS and NRAS exon 2-4). A BRAF mutation is required for predicting poor prognosis...
February 19, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28217439/egfr-targeted-therapy-in-lung-cancer-an-evolving-story
#7
C Bartholomew, L Eastlake, P Dunn, D Yiannakis
Specific oncogenes with driver mutations, such as the Epidermal Growth Factor Receptor (EGFR 1) gene can lead to non-small-cell lung cancer formation. Identification of these oncogenes, their driver mutations and downstream effects allow the targeting of these pathways by drugs. Such personalised therapy has become an important strategy in combating lung cancer and highlights the need to test for these mutations. Tyrosine Kinase Inhibitors (TKIs) against EGFR, such as Erlotinib, are able to halt these tumour promoting properties in non-small-cell lung cancers...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28216890/evaluate-the-antigenotoxicity-and-anticancer-role-of-%C3%AE-sitosterol-by-determining-oxidative-dna-damage-and-the-expression-of-phosphorylated-mitogen-activated-protein-kinases-c-fos-c-jun-and-endothelial-growth-factor-receptor
#8
Ramalingam Sharmila, Ganapathy Sindhu
BACKGROUND: Plant sterols are the major source of micronutrients and have not shown any obvious side effects in human. β-sitosterol is one of the most prevalent phytosterols which have been recorded in ancient medicinal history for its use in the treatment of many chronic diseases, especially cancer. The modulations of mitogen-activated protein kinases' (MAPKs') play a crucial role in the development of human renal cell carcinoma. OBJECTIVE: The aim of the current study is to evaluate the antigenotoxic and anticancer role of β-sitosterol against renal carcinogen...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28213007/effect-of-dasatinib-on-emt-mediated-mechanism-of-resistance-against-egfr-inhibitors-in-lung-cancer-cells
#9
Yuichi Sesumi, Kenichi Suda, Hiroshi Mizuuchi, Yoshihisa Kobayashi, Katsuaki Sato, Masato Chiba, Masaki Shimoji, Kenji Tomizawa, Toshiki Takemoto, Tetsuya Mitsudomi
OBJECTIVE: The epithelial to mesenchymal transition (EMT) is associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in certain non-small cell lung cancers that harbor EGFR mutations. Because no currently available drugs specifically kill cancer cells via EMT, novel treatment strategies that overcome or prevent EMT are needed. A recent report suggested that dasatinib (an ABL/Src kinase inhibitor) inhibits EMT induced by transforming growth factor (TGF)-beta in lung cancer cells (Wilson et al...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28213001/predictive-factors-for-egfr-tyrosine-kinase-inhibitor-retreatment-in-patients-with-egfr-mutated-non-small-cell-lung-cancer-a-multicenter-retrospective-sequence-study
#10
Gee-Chen Chang, Chien-Hua Tseng, Kuo-Hsuan Hsu, Chong-Jen Yu, Cheng-Ta Yang, Kun-Chieh Chen, Tsung-Ying Yang, Jeng-Sen Tseng, Chien-Ying Liu, Wei-Yu Liao, Te-Chun Hsia, Chih-Yen Tu, Meng-Chih Lin, Ying-Huang Tsai, Meng-Jer Hsieh, Wen-Shuo Wu, Yuh-Min Chen
BACKGROUND: Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. MATERIALS AND METHODS: This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212993/efficacy-according-to-blind-independent-central-review-post-hoc-analyses-from-the-phase-iii-randomized-multicenter-ipass-study-of-first-line-gefitinib-versus-carboplatin-paclitaxel-in-asian-patients-with-egfr-mutation-positive-advanced-nsclc
#11
Yi-Long Wu, Nagahiro Saijo, Sumitra Thongprasert, J C-H Yang, Baohui Han, Benjamin Margono, Busayamas Chewaskulyong, Patrapim Sunpaweravong, Yuichiro Ohe, Yukito Ichinose, Jin-Ji Yang, Tony S K Mok, Helen Young, Vincent Haddad, Yuri Rukazenkov, Masahiro Fukuoka
OBJECTIVE: The Phase III, randomized, open-label IPASS study (NCT00322452) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) gefitinib versus carboplatin/paclitaxel for Asian patients with advanced non-small-cell lung cancer (NSCLC) showed that investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were significantly prolonged in patients with EGFR mutation-positive NSCLC who received gefitinib versus patients with EGFR mutation-negative NSCLC...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28211502/bisphosphonates-enhance-antitumor-effect-of-egfr-tkis-in-patients-with-advanced-egfr-mutant-nsclc-and-bone-metastases
#12
Guowei Zhang, Ruirui Cheng, Zengli Zhang, Tao Jiang, Shengxiang Ren, Zhiyong Ma, Sha Zhao, Caicun Zhou, Jun Zhang
Whether bisphosphonates could enhance the effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with EGFR mutation and bone metastases (BM) remains unknown. EGFR mutation status were collected from 1560 patients with NSCLC and BM. 356 NSCLC patients with EGFR mutation and BM were identified. Among them, 91 patients received EGFR-TKIs alone and 105 patients received EGFR-TKIs plus bisphosphonates as first-line therapy. Comparing to TKIs alone, EGFR-TKIs plus bisphosphonates had a statistically significant longer progression-free survival (PFS: 11...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208660/splice-variants-of-the-rtk-family-their-role-in-tumour-progression-and-response-to-targeted-therapy
#13
REVIEW
Cherine Abou-Fayçal, Anne-Sophie Hatat, Sylvie Gazzeri, Beatrice Eymin
Receptor tyrosine kinases (RTKs) belong to a family of transmembrane receptors that display tyrosine kinase activity and trigger the activation of downstream signalling pathways mainly involved in cell proliferation and survival. RTK amplification or somatic mutations leading to their constitutive activation and oncogenic properties have been reported in various tumour types. Numerous RTK-targeted therapies have been developed to counteract this hyperactivation. Alternative splicing of pre-mRNA has recently emerged as an important contributor to cancer development and tumour maintenance...
February 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208047/targeted-therapy-for-chronic-respiratory-disease-a-new-paradigm
#14
Peter G Gibson, Matthew J Peters, Claire E Wainwright
Targeted therapy has emerged as a highly effective treatment approach for chronic respiratory diseases. Many of these conditions have dismal outcomes; however, targeted therapy shows great results for the subgroup who respond. This represents a new way to approach these conditions and offers great promise as a future treatment direction. In severe eosinophilic asthma, therapy that targets the interleukin-5 pathway with monoclonal antibodies leads to a 50% reduction in asthma exacerbations in previously refractory disease...
February 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28207548/egfr-mutation-testing-in-blood-for-guiding-egfr-tyrosine-kinase-inhibitor-treatment-in-patients-with-nonsmall-cell-lung-cancer-a-protocol-for-systematic-review-and-meta-analysis
#15
Jin-Qiu Yuan, Yue-Lun Zhang, Hai-Tao Li, Chen Mao
BACKGROUND: Epidermal growth factor receptor (EGFR) mutation testing in tumor tissue is now a common practice in selecting non-small cell lung cancer (NSCLC) patients for EGFR tyrosine kinase inhibitor (TKI) treatment. However, tumor tissues are often absent or insufficient for the testing. Blood is a potential substitute providing a noninvasive, easily accessible and repeatedly measureable source of genotypic information. However which is the best blood EGFR mutation testing method remains unclear...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28203297/therapeutic-approach-to-treating-patients-with-braf-mutant-lung-cancer-latest-evidence-and-clinical-implications
#16
REVIEW
Adrianus J de Langen, Egbert F Smit
Lung adenocarcinoma is known for its high rate of somatic mutations and genomic rearrangements. The identification of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements that sensitize tumors to specific drugs has changed the therapeutic approach and prognosis in these molecularly-defined subgroups. Several other key genetic alterations have been identified, of which BRAF mutations are found in 4% of non-small cell lung cancer (NSCLC) cases. Targeted drugs against BRAF and downstream MEK were recently approved for the treatment of BRAF-positive melanoma and have entered clinical evaluation in NSCLC...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28202511/amplification-of-egfr-wild-type-alleles-in-non-small-cell-lung-cancer-cells-confers-acquired-resistance-to-mutation-selective-egfr-tyrosine-kinase-inhibitors
#17
Shigenari Nukaga, Hiroyuki Yasuda, Katsuya Tsuchihara, Junko Hamamoto, Keita Masuzawa, Ichiro Kawada, Katsuhiko Naoki, Shingo Matsumoto, Sachiyo Mimaki, Shinnosuke Ikemura, Koichi Goto, Tomoko Betsuyaku, Kenzo Soejima
EGFR-mutated lung cancers account for a significant subgroup of non-small cell lung cancers overall. Third-generation EGFR tyrosine kinase inhibitors (TKI) are mutation-selective inhibitors with minimal effects on wild type EGFR. Acquired resistance develops to these agents, however, the mechanisms are as yet uncharacterized. In this study, we report that the Src-AKT pathway contributes to acquired resistance to these TKI. In addition, amplification of EGFR wild-type alleles but not mutant alleles was sufficient to confer acquired resistance...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197371/prophylactic-vaccination-targeting-erbb3-decreases-polyp-burden-in-a-mouse-model-of-human-colorectal-cancer
#18
David J Bautz, Ang T Sherpa, David W Threadgill
Prophylactic vaccination is typically utilized for the prevention of communicable diseases such as measles and influenza but, with the exception of vaccines to prevent cervical cancer, is not widely used as a means of preventing or reducing the incidence of cancer. Here, we utilize a peptide-based immunotherapeutic approach targeting ERBB3, a pseudo-kinase member of the EGFR/ERBB family of receptor tyrosine kinases, as a means of preventing occurrence of colon polyps. Administration of the peptide resulted in a significant decrease in the development of intestinal polyps in C57BL/6J-Apc(Min) mice, a model of familial adenomatous polyposis (FAP)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196873/lymphotoxin-beta-interacts-with-methylated-egfr-to-mediate-acquired-resistance-to-cetuximab-in-head-and-neck-cancer
#19
Dennis Shin-Shian Hsu, Wei-Lun Hwang, Chiou-Hwa Yuh, Chen-Hsi Chu, Yang-Hui Ho, Pon-Bo Chen, Han-Syuan Lin, Hua-Kuo Lin, Shih-Pei Wu, Chih-Yi Lin, Wen-Hao Hsu, Hsin-Yi Lan, Hsiao-Jung Wang, Shyh-Kuan Tai, Mien-Chie Hung, Muh-Hwa Yang
PURPOSE: In head and neck squamous cell carcinoma (HNSCC), the incidence of RAS mutation, which is the major cause of cetuximab resistance, is relatively rare compared with the other types of cancers, and the mechanism mediating acquired resistance is unclear compared with the driver gene mutation-mediated de novo resistance. Here we investigated the driver gene mutation-independent mechanism for cetuximab resistance in HNSCC. EXPERIMENTAL DESIGN: We used the in vitro-selected and in vivo-selected cetuximab-resistant sublines of HNSCC cell lines for investigating the mechanism of acquired resistance to cetuximab...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28196064/mt4-mmp-and-egfr-expression-levels-are-key-biomarkers-for-breast-cancer-patient-response-to-chemotherapy-and-erlotinib
#20
Cassandre Yip, Pierre Foidart, Joan Somja, Alice Truong, Mehdi Lienard, Emilie Feyereisen, Hélène Schroeder, Stéphanie Gofflot, Anne-Françoise Donneau, Joëlle Collignon, Philippe Delvenne, Nor Eddine Sounni, Guy Jerusalem, Agnès Noël
BACKGROUND: Triple-negative breast cancers (TNBC) are heterogeneous cancers with poor prognosis. We aimed to determine the clinical relevance of membrane type-4 matrix metalloproteinase (MT4-MMP), a membrane type matrix metalloproteinase that interacts with epidermal growth factor receptor (EGFR) overexpressed in >50% of TNBC. METHODS: We conducted a retrospective immunohistochemical analysis on human TNBC samples (n=81) and validated our findings in in vitro and in vivo assays...
February 14, 2017: British Journal of Cancer
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