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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/28220630/clinical-value-of-the-new-international-association-for-the-study-of-lung-cancer-american-thoracic-society-european-respiratory-society-classification-of-lung-adenocarcinoma
#2
Ziwei Guo, Fumei Yi, Wencheng Yin, Yu Zhang, Qian Li, Yangchun Gu, Yu Xiao, Baoshan Cao, Liwen Ma, Li Liang
BACKGROUND: We explored correlations between the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, epidermal growth factor receptor (EGFR) mutation status, and prognosis. METHODS: Data from 293 patients with lung adenocarcinoma were classified according to the new classification. Fisher's exact, χ(2) , and log-rank tests and Cox regression analysis were used to analyze correlations between EGFR mutation status, lung cancer prognosis, and the new histologic subtype...
February 21, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28220486/cetuximab-plus-irinotecan-versus-panitumumab-in-patients-with-refractory-metastatic-colorectal-cancer-in-ontario-canada
#3
Katarzyna J Jerzak, Scott Berry, Yoo-Joung Ko, Craig Earle, Kelvin K W Chan
The addition of irinotecan to an EGFR antibody has previously been shown to improve tumor response rate and time to progression but not overall survival (OS) for refractory metastatic colorectal cancer (mCRC). We assessed the "real world" effectiveness and toxicity of the combination versus monotherapy. In Ontario, Canada universal public funding is available for either cetuximab plus irinotecan (Cmab+I) combination therapy or panitumumab (Pmab) monotherapy, only in patients with refractory non-mutated RAS mCRC...
February 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28220124/in-vivo-efficacy-of-umbilical-cord-blood-stem-cell-derived-nk-cells-in-the-treatment-of-metastatic-colorectal-cancer
#4
John P Veluchamy, Silvia Lopez-Lastra, Jan Spanholtz, Fenna Bohme, Nina Kok, Daniëlle A M Heideman, Henk M W Verheul, James P Di Santo, Tanja D de Gruijl, Hans J van der Vliet
Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RAS(wt) metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219203/-precision-first-line-therapy-for-advanced-non-small-cell-lung-cancer-patients-harboring-egfr-mutation
#5
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
#6
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/28219200/-application-strategies-of-the-third-generation-egfr-tki-in-the-context-of-precision-medicine
#7
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/28219199/-improving-the-internal-medical-care-to-set-up-a-leading-model-for-precision-medicine-development-in-lung-cancer
#8
B H Han
Lung cancer still remains the leading cause of cancer-related death worldwide. Recent development of molecular targeted therapies, especially the emergence of epidermal growth factor receptor (EGFR) inhibitors, has made an enormous progress for the treatment of non-small cell lung cancer (NSCLC). However, targeted therapy still faces many problems including acquired resistance. Several clinical trials have proved that targeted therapy can significantly improve the progression-free survival (PFS), but there are still many things needed to be improved...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28219002/molecular-testing-for-gastrointestinal-cancer
#9
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
#10
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
#11
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/28216373/tweak-stimulated-macrophages-inhibit-metastasis-of-epithelial-ovarian-cancer-via-exosomal-shuttling-of-microrna
#12
Yuan Hu, Dong Li, Anyue Wu, Xingdi Qiu, Wen Di, Lei Huang, Lihua Qiu
Exosomal-miRNAs are emerging as mediators of crosstalk between tumor cells and macrophages. In this study, we observed that exosomes derived from TWEAK-stimulated macrophages (TMs) could be internalized by epithelial ovarian cancer (EOC) cells and inhibit cell metastasis. Through a miRNA microarray analysis, we identified 19 miRNAs that are differentially expressed in exosomes derived from macrophages treated with or without TWEAK. The study validated that TWEAK not only increased the levels of microRNA-7 (miR-7) in macrophages and its secreted exosomes but also resulted in an elevated level of miR-7 in recipient EOC cells, which eventually reduced the activity of the EGFR/AKT/ERK1/2 pathway...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28215720/tackling-the-next-generation-of-resistance-in-egfr-mutant-lung-cancer
#13
EDITORIAL
Zofia Piotrowska, Lecia V Sequist
No abstract text is available yet for this article.
March 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28214977/braf-mutated-colorectal-cancer-what-is-the-optimal-strategy-for-treatment
#14
REVIEW
Romain Cohen, Pascale Cervera, Magali Svrcek, Anna Pellat, Chantal Dreyer, Aimery de Gramont, Thierry André
The BRAF activating mutation, harbored by approximately 10% of colorectal cancers (CRC), confers dramatic prognosis to advanced diseases. In early-stage setting, the identification of the BRAF mutation does not impact the therapeutic decision. Yet, the BRAF mutation could be considered as a stratification factor in adjuvant trials, because of its prognostic impact after relapse. Moreover, both BRAF mutation and mismatch repair (MMR) statuses should be determined in all CRC to help identify sporadic tumors versus Lynch syndrome-related tumors...
February 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#15
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28213365/fda-approval-summary-tas-102
#16
Leigh Marcus, Steven J Lemery, Sachia Khasar, Emily Wearne, Whitney S Helms, Weishi Yuan, Kun He, Xianhua Cao, Jingyu Yu, Hong Zhao, Yaning Wang, Olen Stephens, Erika Englund, Rajiv Agarwal, Patricia Keegan, Richard Pazdur
FDA approved TAS-102 (Lonsurf, Taiho Oncology, Inc.) for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. In an international, multicenter, double-blinded, placebo-controlled trial (TPU-TAS-102-301, herein referred to as RECOURSE), 800 patients with previously treated mCRC were randomly allocated (2:1) to receive either TAS-102 35mg/m2 orally twice daily after meals on Days 1-5 and 8-12 of each 28-day cycle (n=534) or matching placebo (n=266)...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28213007/effect-of-dasatinib-on-emt-mediated-mechanism-of-resistance-against-egfr-inhibitors-in-lung-cancer-cells
#17
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
#18
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
#19
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/28212572/concurrent-gene-alterations-with-egfr-mutation-and-treatment-efficacy-of-egfr-tkis-in-chinese-patients-with-non-small-cell-lung-cancer
#20
Wentao Hu, Yahui Liu, Jian Chen
PURPOSE: We investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy of EGFR-TKIs treatment. METHODS: Three hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET fusion genes based on reverse transcription PCR...
February 15, 2017: Oncotarget
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