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https://www.readbyqxmd.com/read/29775935/design-synthesis-antiproliferative-activity-and-docking-studies-of-quinazoline-derivatives-bearing-2-3-dihydro-indole-or-1-2-3-4-tetrahydroquinoline-as-potential-egfr-inhibitors
#1
Yiqiang OuYang, Wensheng Zou, Liang Peng, Zunhua Yang, Qidong Tang, Mengzi Chen, Shuang Jia, Hong Zhang, Zhou Lan, Pengwu Zheng, Wufu Zhu
Eight series of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline were designed, synthesized and evaluated for the IC50 values against three cancer cell lines (A549, MCF-7 and PC-3). Most of the forty nine target compounds showed excellent antiproliferative activity against one or several cancer cell lines. The compound 13a showed the best activity against A549, MCF-7 and PC-3 cancer cell lines, with the IC50 values of 1.09 ± 0.04 μM, 1.34 ± 0.13 μM and 1.23 ± 0...
May 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29775809/transient-asymptomatic-pulmonary-opacities-during-osimertinib-treatment-and-its-clinical-implication
#2
Hansang Lee, Ho Yun Lee, Jong-Mu Sun, Se-Hoon Lee, Youjin Kim, Song Ee Park, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
INTRODUCTION: Osimertinib is an oral, potent, irreversible 3rd generation EGFR tyrosine kinase inhibitor (TKI) approved for the treatment of T790M positive non-small cell lung cancer (NSCLC) patients who failed 1st or 2nd generation EGFR TKIs. Interstitial lung disease (ILD) is a rare complication with osimertinib, occurring in 1-3%. Recently, relatively high incidence of transient asymptomatic pulmonary opacities (TAPOs) which are different from ILD has been described. However, its clinical implication has not been fully determined yet...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29774061/immunotherapy-in-non-metastatic-non-small-cell-lung-cancer-can-the-benefits-of-stage-iv-therapy-be-translated-into-earlier-stages
#3
REVIEW
Griet Deslypere, Dorothée Gullentops, Els Wauters, Johan Vansteenkiste
Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR ) activating mutations or anaplastic lymphoma kinase ( ALK ) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29773991/first-biologic-drug-in-the-treatment-of-ras-wild-type-metastatic-colorectal-cancer-anti-egfr-or-bevacizumab-results-from-a-meta-analysis
#4
REVIEW
Alessandro Ottaiano, Alfonso De Stefano, Monica Capozzi, Anna Nappi, Chiara De Divitiis, Carmela Romano, Lucrezia Silvestro, Antonino Cassata, Rossana Casaretti, Salvatore Tafuto, Michele Caraglia, Massimiliano Berretta, Guglielmo Nasti, Antonio Avallone
Introduction: We performed a meta-analysis in order to analyze and quantify the effect on survival of starting therapy in RAS wild-type (wt) metastatic colorectal cancer (mCRC) patients with anti-EGFR agents or bevacizumab. Patients and Methods: Randomized, phase II or III, clinical trials reporting overall survival (OS) in RAS wt mCRC patients treated with first-line chemotherapy (CT) associated with bevacizumab or anti-EGFR agents were selected. The primary end-point of this meta-analysis was OS; findings were depicted in classical Forest plots...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773864/igg-single-chain-trail-fusion-proteins-for-tumour-therapy
#5
Martin Siegemund, Felix Schneider, Meike Hutt, Oliver Seifert, Ines Müller, Dagmar Kulms, Klaus Pfizenmaier, Roland E Kontermann
Single-chain formats of TNF-related apoptosis inducing ligand (scTRAIL) can serve as effector components of tumour-associated antigen-targeted as well as non-targeted fusion proteins, being characterized by high tumour cell-specific induction of apoptosis through death receptor activation. We studied the suitability of immunoglobulin G as a scaffold for oligovalent and bispecific TRAIL fusion proteins. Thus, we developed novel targeted hexa- and dodecavalent IgG-scTRAIL molecules by fusing scTRAIL to the C-terminus of either light (LC-scTRAIL) or heavy immunoglobulin chain (HC-scTRAIL), or to both ends (LC/HC-scTRAIL) of the anti-EGFR IgG antibody hu225...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29772692/insurance-coverage-policies-for-pharmacogenomic-and-multi-gene-testing-for-cancer
#6
Christine Y Lu, Stephanie Loomer, Rachel Ceccarelli, Kathleen M Mazor, James Sabin, Ellen Wright Clayton, Geoffrey S Ginsburg, Ann Chen Wu
Insurance coverage policies are a major determinant of patient access to genomic tests. The objective of this study was to examine differences in coverage policies for guideline-recommended pharmacogenomic tests that inform cancer treatment. We analyzed coverage policies from eight Medicare contractors and 10 private payers for 23 biomarkers (e.g., HER2 and EGFR ) and multi-gene tests. We extracted policy coverage and criteria, prior authorization requirements, and an evidence basis for coverage. We reviewed professional society guidelines and their recommendations for use of pharmacogenomic tests...
May 16, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29772559/gitr-domain-inside-car-co-stimulates-activity-of-car-t-cells-against-cancer
#7
Vita M Golubovskaya, Robert Berahovich, Qumiao Xu, Hua Zhou, Shirley Xu, Jasper Guan, Hizkia Harto, Le Li, Lijun Wu
T cells expressing Chimeric antigen receptors or CAR-T cells are used as a novel treatment against hematological and solid cancers. In this report, we designed CAR with glucocorticoid-induced TNFR-related protein (GITR) co-stimulatory domain to study its ability to co-activate CAR-T cells. EGFR-GITR-CD3 CAR-T cells were cytotoxic against EGFR-positive: pancreatic and ovarian cancer cells but not against EGFR-negative cancer cells. The cytotoxic activity of EGFR-GITR-CD3 CAR-T cells was comparable or better than EGFR-28-CD3 or EGFR-41BB-CD3 CAR-T cells...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29771169/associations-between-skin-rash-treatment-outcome-and-single-nucleotide-polymorphisms-in-head-and-neck-cancer-patients-receiving-the-egfr-inhibitor-zalutumumab-results-from-the-dahanca-19-trial
#8
Line Brøndum, Jan Alsner, Brita Singers Sørensen, Christian Maare, Jørgen Johansen, Hanne Primdahl, Jan Folkvard Evensen, Claus Andrup Kristensen, Lisbeth Juhler Andersen, Jens Overgaard, Jesper Grau Eriksen
PURPOSE: To study the associations between development of moderate to severe skin rash, clinical outcome, and single nucleotide polymorphisms (SNPs) in candidate genes in head and neck cancer patients from the DAHANCA 19 trial receiving the EGFR-inhibitor zalutumumab concurrently with radiation treatment. MATERIAL AND METHODS: 310 patients were included from the zalutumumab-arm of the DAHANCA 19 study. Nine SNPs in the candidate genes EGFR, EGF, AREG, FCGR2A, FCGR3A, and CCND1 were successfully determined in 294 patients...
May 17, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29770473/icotinib-enhances-lung-cancer-cell-radiosensitivity-in-vitro-and-in-vivo-by-inhibiting-mapk-erk-and-akt-activation
#9
Yonghong Fu, Sen Zhang, Dongjie Wang, Jing Wang
Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29769385/phase-ii-study-of-irinotecan-plus-panitumumab-as-second-line-therapy-for-patients-with-advanced-esophageal-adenocarcinoma
#10
Harry Yoon, Anita Choudhary, Ramla Kosozi, Gurvinder Singh Bali, Ali Zaidi, Ajlan Atasoy, Arlene A Forastiere, Michael K Gibson
LESSON LEARNED: Panitumumab plus irinotecan is not active for the treatment of esophageal adenocarcinoma. BACKGROUND: Esophageal adenocarcinoma (EAC) is a lethal cancer with increasing incidence. Panitumumab (Pa) is a fully humanized IgG2 monoclonal antibody against human EGFR. Cetuximab (Cx) combined with irinotecan (Ir) is active for second-line treatment of colorectal cancer. This phase II study was designed to evaluate Pa plus Ir as second-line therapy for advanced EAC...
May 16, 2018: Oncologist
https://www.readbyqxmd.com/read/29768721/real-world-study-of-regimen-containing-bevacizumab-as-first-line-therapy-in-chinese-patients-with-advanced-non-small-cell-lung-cancer
#11
Puyuan Xing, Yuxin Mu, Yan Wang, Xuezhi Hao, Yixiang Zhu, Xingsheng Hu, Hongyu Wang, Peng Liu, Lin Lin, Zhijie Wang, Junling Li
BACKGROUND: Large scale randomized controlled trials have demonstrated that the use of bevacizumab in addition to chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) conveys significant survival benefits. We explored the clinical impact of a first-line regimen containing bevacizumab (B+) versus a non-bevacizumab regimen (non-B) in advanced non-squamous NSCLC (NS-NSCLC) patients in a real world setting. METHODS: The medical records of patients with advanced NS-NSCLC who received first-line therapy with or without bevacizumab were retrospectively collected...
May 16, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29768260/carboplatin-dosing-accuracy-by-estimation-of-glomerular-filtration-versus-creatinuria-in-cancer-patients
#12
Noiver Graciano Vera, Luis Pino Villarreal, Jenny Ureña Vargas
BACKGROUND: The glomerular filtration rate (GFR) is essential for calculating the dose and the monitoring of carboplatin. Although GFR measurement (mGFR) by external markers is ideal, in most cases these are not employed; the most used method is GFR estimation (eGFR) by formulae, hence the need to identify the formula with the best performance. METHODS: Patients admitted between 2011 and 2017 and diagnosed with ovarian, endometrial, lung, esophageal, or testicular cancer were assessed retrospectively...
May 16, 2018: Chemotherapy
https://www.readbyqxmd.com/read/29767438/serum-sp70-is-a-sensitive-predictor-of-chemotherapy-response-in-patients-with-advanced-nonsmall-cell-lung-cancer
#13
Jingping Liu, Wei Zhang, Min Gu, Yazhou Ji, Lu Yang, Xiangjun Cheng, Xuelian Xiao, Jian Xu, Chunrong Gu, Jiexin Zhang, Shichang Zhang, Dan Chen, Shiyang Pan
SP70 is a novel tumor biomarker in patients with nonsmall cell lung cancer (NSCLC). However, its role as a marker for predicting the response to chemotherapy for patients with advanced NSCLC has not been investigated. A total of 152 patients were enrolled. Serum SP70, carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and neuron-specific enolase (NSE) were detected before and after 2 cycles of chemotherapy. The correlation between serum tumor biomarker levels and chemotherapy responses and their association with epidermal growth factor receptor (EGFR) mutation status and progression-free survival (PFS) were analyzed...
May 16, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29766737/identification-of-small-molecule-egfr-allosteric-inhibitors-by-high-throughput-docking
#14
Fabiana Caporuscio, Annachiara Tinivella, Valentina Restelli, Marta S Semrau, Luca Pinzi, Paola Storici, Massimo Broggini, Giulio Rastelli
AIM: The EGFR inhibitors represent the first-line treatment of non-small-cell lung cancer. However, the emergence of resistance urgently requires the development of new inhibitors targeting drug-resistant mutants. METHODOLOGY: A recently released structure of an EGFR kinase domain in complex with an allosteric inhibitor and a mutant protein model derived from it were used to set up a low-cost high-throughput docking protocol for the fast identification of EGFR allosteric inhibitors...
May 16, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29765773/optimising-the-use-of-cetuximab-in-the-continuum-of-care-for-patients-with-metastatic-colorectal-cancer
#15
REVIEW
Richard M Goldberg, Clara Montagut, Zev A Wainberg, Philippe Ronga, François Audhuy, Julien Taieb, Sebastian Stintzing, Salvatore Siena, Daniele Santini
The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with chemotherapy is a standard of care in the first-line treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC) and has demonstrated efficacy in later lines. Progressive disease (PD) occurs when tumours develop resistance to a therapy, although controversy remains about whether PD on a combination of chemotherapy and targeted agents implies resistance to both components. Here, we propose that some patients may gain additional clinical benefit from the reuse of cetuximab after having PD on regimens including cetuximab in an earlier treatment line...
2018: ESMO Open
https://www.readbyqxmd.com/read/29765563/targeted-therapies-in-the-management-of-locally-advanced-and-metastatic-pancreatic-cancer-a-systematic-review
#16
REVIEW
Anjali V Sheahan, Andrew V Biankin, Christopher R Parish, Levon M Khachigian
Pancreatic cancer has a dismal prognosis particularly in patients presenting with unresectable tumors. We performed a bibliometric analysis of clinical trials for pancreatic cancer conducted between 2014-2016 focusing on patients that presented with unresectable (locally advanced or metastatic) tumors. We discuss a range of studies that employed FOLFIRINOX, the gemcitabine + nab-paclitaxel combination and studies that used molecularly-targeted therapy. Major areas of focus have been dual targeting of EGFR and VEGFR, immunotherapy or a multimodal approach - combining chemotherapy with radiotherapy...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765525/clinical-characteristics-of-non-small-cell-lung-cancer-harboring-mutations-in-exon-20-of-egfr-or-her2
#17
Masayuki Takeda, Kazuko Sakai, Hidetoshi Hayashi, Kaoru Tanaka, Junko Tanizaki, Takayuki Takahama, Koji Haratani, Kazuto Nishio, Kazuhiko Nakagawa
Unlike common epidermal growth factor receptor gene ( EGFR ) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene ( HER2 ) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exon-20 mutations of EGFR or HER2 as detected by routine application of an amplicon-based next-generation sequencing panel...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764856/-tp53-stk11-and-egfr-mutations-predict-tumor-immune-profile-and-the-response-to-anti-pd-1-in-lung-adenocarcinoma
#18
Jerome Biton, Audrey Mansuet-Lupo, Nicolas Pécuchet, Marco Alifano, Hanane Ouakrim, Jennifer Arrondeau, Pascaline Boudou-Rouquette, Francois Goldwasser, Karen Leroy, Jeremy Goc, Marie Wislez, Claire Germain, Pierre Laurent-Puig, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Ronald Herbst, Hélène F Blons, Diane Damotte
PURPOSE: By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. EXPERIMENTAL DESIGN: We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29764596/-a-case-report-of-advanced-lung-adenocarcinoma-harboring-kras-mutation-treated-with-anlotinib
#19
Yudong Su, Zhaoting Meng, Xiaoyan Xu, XinYue Wang, Ran Zuo, Yunxia Hou, Kai Li, Peng Chen
In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29764594/-research-progress-of-kras-mutation-in-non-small-cell-lung-cancer
#20
Lei Liu, Suju Wei
Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all patients with lung cancer, the majority of patients with lung cancer at the time of diagnosis is in the advanced stage. The development of target therapy based on has changed the mode of treatment in patients with advanced NSCLC. In NSCLC, epidermal growth factor receptor mutation (EGFR) fusion with echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) has been shown to be a powerful biomarker...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
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