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https://www.readbyqxmd.com/read/29331420/dacomitinib-antagonizes-multidrug-resistance-mdr-in-cancer-cells-by-inhibiting-the-efflux-activity-of-abcb1-and-abcg2-transporters
#1
Ying-Fang Fan, Wei Zhang, Leli Zeng, Zi-Ning Lei, Chao-Yun Cai, Pranav Gupta, Dong-Hua Yang, Qingbin Cui, Zuo-Dong Qin, Zhe-Sheng Chen, Louis D Trombetta
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Numerous mechanisms have been recognized that cause MDR, but one of the most important mechanisms is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, through which the efflux of various anticancer drugs against their concentration gradients is powered by ATP. In recent years, small molecular tyrosine kinase inhibitors (TKIs) have been developed for treatment in various human cancers overexpressing epidermal growth factor receptor (EGFR)...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29328407/estrogen-receptor-%C3%AE-1-activation-accelerates-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer
#2
Shengling Fu, Changyu Liu, Quanfu Huang, Sheng Fan, Hexiao Tang, Xiangning Fu, Bo Ai, Yongde Liao, Qian Chu
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR‑TKIs) have revolutionized the treatment of patients with advanced EGFR-mutant NSCLC. However, drug resistance eventually develops in the majority of patients despite an excellent initial response. The present study aimed to investigate the mechanism of acquired resistance to EGFR-TKIs and to explore strategies to overcome the resistance to EGFR-TKIs from a gender perspective...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327159/efficacy-and-safety-of-third-line-molecular-targeted-therapy-in-metastatic-renal-cell-carcinoma-resistant-to-first-line-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitor-and-second-line-therapy
#3
Hiroki Ishihara, Toshio Takagi, Tsunenori Kondo, Hidekazu Tachibana, Kazuhiko Yoshida, Kenji Omae, Junpei Iizuka, Hirohito Kobayashi, Kazunari Tanabe
BACKGROUND: The number of studies evaluating the efficacy and safety of third-line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is limited. METHODS: The data for 48 patients with disease progression after first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI) and second-line targeted therapy were evaluated. Patients with prior cytokine therapy were excluded. Overall survival (OS) after first- and second-line therapy initiation was compared between patients with and without third-line therapy...
January 11, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29327061/egfr-tki-associated-interstitial-pneumonitis-in-nivolumab-treated-patients-with-non-small-cell-lung-cancer
#4
Yasuo Oshima, Tetsuya Tanimoto, Koichiro Yuji, Arinobu Tojo
Importance: Nivolumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are now the standard-of-care therapies in non-small cell lung cancer (NSCLC). Although EGFR-TKIs are well understood and have well-defined safety profiles, our experience with immune checkpoint inhibitors is still growing, particularly regarding the use of combinations of different classes of antitumor agents, including both the concomitant and sequential use of such agents. Objective: To determine whether nivolumab increases EGFR-TKI-associated interstitial pneumonitis (IP)...
January 11, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29325035/amplicon-based-next-generation-sequencing-of-plasma-cell-free-dna-for-detection-of-driver-and-resistance-mutations-in-advanced-non-small-cell-lung-cancer
#5
N Guibert, Y Hu, N Feeney, Y Kuang, V Plagnol, G Jones, K Howarth, J F Beeler, C P Paweletz, G R Oxnard
Background: Genomic analysis of plasma cell-free DNA is transforming lung cancer care, however available assays are limited by cost, turnaround time, and imperfect accuracy. Here we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). Methods: Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1 and other rare genotypes) were collected while on therapy and analyzed, blinded to tumor genotype...
January 9, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29321482/enhanced-yap-expression-leads-to-egfr-tki-resistance-in-lung-adenocarcinomas
#6
Ting-Fang Lee, Yu-Chi Tseng, Phung Anh Nguyen, Yu-Chuan Li, Chao-Chi Ho, Cheng-Wen Wu
Epidermal growth factor receptor (EGFR) mutation is prevalently expressed in lung adenocarcinoma cases and acts as one of the major driving oncogenes. EGFR tyrosine kinase inhibitors (TKIs) have been used in patients with EGFR-mutant as an effective targeted therapy in lung adenocarcinoma, but drug resistance and tumor recurrence inevitably occurs. Recently, Yes-associate protein (YAP) has been reported to promote multiple cancer cell properties, such as promoting cell proliferation, epithelial-mesenchymal transition and drug resistance...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318404/does-alk-rearrangement-predict-favorable-response-to-the-therapy-of-bevacizumab-plus-pemetrexed-in-advanced-non-small-cell-lung-cancer-case-report-and-literature-review
#7
Zhichao Liu, Youting Bao, Butuo Li, Xindong Sun, Linlin Wang
BACKGROUND: Advanced ALK-rearranged non-small cell lung cancer (NSCLC) patients will develop acquired resistance after anaplastic lymphoma kinase (ALK) inhibitors therapies. Vascular endothelial growth factor-A (VEGF-A) production and tumor vessel formation were found to be more significantly enriched in ALK-rearrangement NSCLC than that in epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene mutated NSCLC. However, the correlation between ALK rearrangement and the efficacy of bevacizumab (a recombinant humanized IgG1 monoclonal antibody targeting VEGF-A) was still elusive...
January 9, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29317963/neutrophil-to-lymphocyte-ratio-predicts-overall-survival-of-advanced-non-small-cell-lung-cancer-harboring-mutant-epidermal-growth-factor-receptor
#8
Seigo Minami, Yoshitaka Ogata, Shouichi Ihara, Suguru Yamamoto, Kiyoshi Komuta
Background: Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be prognostic biomarkers in various cancers, including non-small cell lung cancer (NSCLC). However, little has been known about these two ratios for a specific population of NSCLC harboring active epidermal growth factor receptor (EGFR) mutation. Methods: We retrospectively reviewed electrical medical records of 152 patients who met the following criteria: NSCLC harboring mutant EGFR, EGFR-tyrosine kinase inhibitor (EGFR-TKI) monotherapy initiated between October 2007 and February 2017 at our hospital, stage III-IV or post-surgical recurrence...
December 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/29317428/small-cell-transformation-of-alk-rearranged-non-small-cell-adenocarcinoma-of-the-lung
#9
Agnes Balla, Kenneth J Hampel, Farrah Khan, Dara L Aisner, Nikoletta Sidiropoulos
Anaplastic lymphoma kinase (ALK) gene rearrangements are present in approximately 5% of non-small-cell lung cancers (NSCLCs). These rearrangements occur because of a chromosomal inversion within the short arm of chromosome 2, which results in the formation of the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion oncogene. While NSCLC transformation to SCLC is a rare phenomenon described in EGFR mutant cancers primarily after treatment with targeted therapy, it is exceedingly rare in ALK rearranged adenocarcinomas (Toyokawa et al...
January 9, 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29317191/randomized-double-blind-phase-ib-iii-study-of-erlotinib-with-ramucirumab-or-placebo-in-previously-untreated-egfr-mutant-metastatic-non-small-cell-lung-cancer-relay-phase-ib-results
#10
Martin Reck, Edward B Garon, Luis Paz-Ares, Santiago Ponce, Jesus Corral Jaime, Oscar Juan, Ernest Nadal, Katsuyuki Kiura, Ryan C Widau, Shuang He, Rita Dalal, Pablo Lee, Kazuhiko Nakagawa
BACKGROUND: Despite the likelihood of an initial response to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), EGFR-mutant non-small-cell lung cancer (NSCLC) patients develop disease progression. Antiangiogenic agents in combination with an EGFR TKI might provide additional benefit in patients with EGFR-mutant NSCLC. In this article we report safety, exposure, and progression-free survival (PFS) results for part A (phase Ib) of RELAY, a randomized, double-blind, phase Ib/III study investigating safety and efficacy of erlotinib (EGFR TKI) with ramucirumab (anti-vascular endothelial growth factor receptor-2 antibody) or placebo in first-line EGFR-mutant stage IV NSCLC...
November 21, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29316665/towards-comprehension-of-the-abcb1-p-glycoprotein-role-in-chronic-myeloid-leukemia
#11
REVIEW
Raquel C Maia, Flavia C Vasconcelos, Paloma S Souza, Vivian M Rumjanek
Abstract: The introduction of imatinib (IM), a BCR-ABL1 tyrosine kinase inhibitor (TKI), has represented a significant advance in the first-line treatment of chronic myeloid leukemia (CML). However, approximately 30% of patients need to discontinue IM due to resistance or intolerance to this drug. Both resistance and intolerance have also been observed in treatment with the second-generation TKIs-dasatinib, nilotinib, and bosutinib-and the third-generation TKI-ponatinib. The mechanisms of resistance to TKIs may be BCR-ABL1-dependent and/or BCR-ABL1-independent...
January 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29316075/monitoring-tki-therapeutic-responses-with-the-panel-of-metabolic-biomarkers-in-the-chronic-myeloid-leukemia-patients
#12
Bingyu Yang, Chang Wang, Yiyu Xie, Liangjing Xu, Xiaojin Wu, Depei Wu
To investigate the potential biomarkers associated with Chronic Myeloid Leukemia (CML), reveal the metabolite changes related to the continuous phases of tyrosine kinase inhibitors (TKI) and find the potential biomarkers associated with treatment effects. 52 patients with CML and matched 26 healthy people were enrolled as discovery set. Another 194 randomly selected CML patients treated with TKI were chosen as external validation set. Plasma samples from the patients and controls were profiled by using gas chromatography-mass spectrometry (GC-MS) based metabonomic approach...
January 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29315500/long-term-outcome-of-dasatinib-first-line-treatment-in-gastrointestinal-stromal-tumor-a-multicenter-2-stage-phase-2-trial-swiss-group-for-clinical-cancer-research-56-07
#13
Michael Montemurro, Angela Cioffi, Julien Dômont, Piotr Rutkowski, Arnaud D Roth, Roger von Moos, Roman Inauen, Maud Toulmonde, Roger O Burkhard, Claudio Knuesli, Sebastian Bauer, Philippe Cassier, Heike Schwarb, Axel Le Cesne, Dieter Koeberle, Daniela Bärtschi, Daniel Dietrich, Christine Biaggi, John Prior, Serge Leyvraz
BACKGROUND: Tyrosine kinase inhibitors (TKIs) have improved the outcome of patients with gastrointestinal stromal tumors (GISTs), but most patients eventually develop resistance and progress. Dasatinib is a potent inhibitor of BCR-ABL, KIT, and SRC family kinases as well as imatinib-resistant cells. In GISTs, response evaluation is routinely done using computed tomography (CT) and 18 F-fluorodeoxyglucose positron emission tomography coupled to CT (FDG-PET/CT) for early response assessment and outcome prediction...
January 9, 2018: Cancer
https://www.readbyqxmd.com/read/29312741/disease-free-survival-improved-by-use-of-adjuvant-egfr-tyrosine-kinase-inhibitors-in-resectable-non-small-cell-lung-cancer-an-updated-meta-analysis
#14
Yonggang Yuan, Qingyuan Huang, Chang Gu, Haiquan Chen
Background: A previous meta-analysis of our research team suggested survival advantage from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after surgery in patients with EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to follow up on the findings of the previous one and presents our latest updates through the past few years. Methods: The study advanced the previous meta-analysis and included a comprehensive range of relevant studies in PubMed...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29312652/tyrosine-kinase-inhibitor-sensitive-pdgfr%C3%AE-mutations-in-gist-two-cases-and-review-of-the-literature
#15
Pieter A Boonstra, Jourik A Gietema, Albert J H Suurmeijer, Matthew R Groves, Fernando de Assis Batista, Ed Schuuring, Anna K L Reyners
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal malignancies of the gastrointestinal tract. Most GISTs harbor a c-KIT (80%) or a PDGFRα (10%) mutation that leads to constitutive activation of the tyrosine kinase receptor. Response to treatment with tyrosine kinase inhibitors (TKIs) is dependent on mutational status of the tumor. The most common mutation in PDGFRα, D842V, is known to be imatinib resistant. Almost all other PDGFRα mutations are imatinib sensitive. We describe two patients with a PDGFRα exon 18 mutated GIST responding to treatment with TKIs...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312610/inhibitor-repurposing-reveals-alk-ltk-fgfr-ret-and-trk-kinases-as-the-targets-of-azd1480
#16
Iva Gudernova, Lukas Balek, Miroslav Varecha, Jana Fialova Kucerova, Michaela Kunova Bosakova, Bohumil Fafilek, Veronika Palusova, Stjepan Uldrijan, Lukas Trantirek, Pavel Krejci
Many tyrosine kinase inhibitors (TKIs) have failed to reach human use due to insufficient activity in clinical trials. However, the failed TKIs may still benefit patients if their other kinase targets are identified by providing treatment focused on syndromes driven by these kinases. Here, we searched for novel targets of AZD1480, an inhibitor of JAK2 kinase that recently failed phase two cancer clinical trials due to a lack of activity. Twenty seven human receptor tyrosine kinases (RTKs) and 153 of their disease-associated mutants were in-cell profiled for activity in the presence of AZD1480 using a newly developed RTK plasmid library...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312572/comparison-of-alk-status-between-primary-and-corresponding-lymph-node-metastatic-tumors-in-lung-cancer-patients
#17
Qiqi Gao, Honghai Ma, Bo Wang, Yake Yao, Jianya Zhou, Jianying Zhou
Background: The anaplastic lymphoma kinase (ALK) protein has recently become a promising target in the treatment of non-small cell lung carcinomas(NSCLC) patients with ALK translocation because of the high response rates obtained with an ALK inhibitor. ALK translocations are present in approximately 3-5% of NSCLC patients. According to the literature, little information about the relationship of ALK status between the primary tumor and metastatic sites has been reported. We intended to determine whether the ALK translocations of primary lung cancers are consistent with those in corresponding metastatic lymph node tumors...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312564/azacitidine-combined-with-the-selective-flt3-kinase-inhibitor-crenolanib-disrupts-stromal-protection-and-inhibits-expansion-of-residual-leukemia-initiating-cells-in-flt3-itd-aml-with-concurrent-epigenetic-mutations
#18
Anne-Kathrin Garz, Saskia Wolf, Sonja Grath, Verena Gaidzik, Stefan Habringer, Binje Vick, Martina Rudelius, Christoph Ziegenhain, Sylvia Herold, Marie-Theresa Weickert, Martha Smets, Christian Peschel, Robert A J Oostendorp, Sebastian Bultmann, Irmela Jeremias, Christian Thiede, Konstanze Döhner, Ulrich Keller, Katharina S Götze
Effectively targeting leukemia-initiating cells (LIC) in FLT3-ITD-mutated acute myeloid leukemia (AML) is crucial for cure. Tyrosine kinase inhibitors (TKI) have limited impact as single agents, failing to eradicate LIC in the bone marrow. Using primary AML samples and a patient-derived xenograft model, we investigated whether combining the FLT3-selective TKI crenolanib with the hypomethylating agent azacitidine (AZA) eliminates FLT3-ITD LIC and whether efficacy of this combination depends on co-existing mutations...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312548/mimicking-the-bim-bh3-domain-overcomes-resistance-to-egfr-tyrosine-kinase-inhibitors-in-egfr-mutant-non-small-cell-lung-cancer
#19
Jinjing Xia, Hao Bai, Bo Yan, Rong Li, Minhua Shao, Liwen Xiong, Baohui Han
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are widely applied to treat EGFR-mutant non-small cell lung cancer (NSCLC). BIM is a BH3 domain-containing protein encoded by BCL2L11. Some EGFR-mutant NSCLC patients showing BIM deletion polymorphism are resistant to EGFR TKIs. We retrospectively investigated BIM deletion polymorphism in NSCLC patients, its correlation with EGFR TKI (erlotinib) resistance, and the mechanism underlying the drug resistance. Among 245 EGFR-mutant NSCLC patients examined, BIM deletion polymorphism was detected in 43 (12...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29310021/therapeutic-effects-of-tyrosine-kinase-inhibitors-and-subtypes-of-bcr-abl1-transcripts-in-japanese-chronic-myeloid-leukemia-patients-with-three-way-chromosomal-translocations
#20
Koiti Inokuchi, Kazutaka Nakayama, Tetsuzo Tauchi, Tomoiku Takaku, Norio Yokose, Hiroki Yamaguchi, Takashi Kumagai, Norio Komatsu, Kazuma Ohyashiki
We analyzed the clinical responses to thyrosine kinase inhibitors (TKIs) and the molecular and cytogenetic characteristics of 18 chronic myeloid leukemia (CML) patients with 3-way chromosomal translocations. The patients were 14 men and 4 women, aged 23-75 years (median 57 years). The Sokal risk was low in 12 patients, intermediate in 4 patients, and high in 2 patients. Newly identified translocation breakpoints were seen in 7 of the 18 patients. Three patients had the same breakpoints of t(9;22;11)(q34;q11...
January 3, 2018: Leukemia Research
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