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https://www.readbyqxmd.com/read/28213007/effect-of-dasatinib-on-emt-mediated-mechanism-of-resistance-against-egfr-inhibitors-in-lung-cancer-cells
#1
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
#2
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
#3
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/28210267/mir-30-family-potentially-targeting-pi3k-siah2-predicted-interaction-network-represents-a-novel-putative-theranostic-panel-in-non-small-cell-lung-cancer
#4
Lawrence W C Chan, Fengfeng Wang, Fei Meng, Lili Wang, Sze Chuen Cesar Wong, Joseph S K Au, Sijun Yang, William C S Cho
Non-small cell lung cancer (NSCLC) comprises about 84% of all lung cancers. Many treatment options are available but the survival rate is still very low due to drug resistance. It has been found that phosphoinositide-3-kinase (PI3K) affects sensitivity to tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib. Expression level of seven in absentia homolog 2 (SIAH2), an E3 ubiquitin-protein ligase, is upregulated in NSCLC and correlated with tumor grade. However, the relationship between PI3K and SIAH2 remains unclear and therefore it is not known whether they can act as treatment co-targets and theranostic dual markers for overcoming TKI resistance...
2017: Frontiers in Genetics
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
#5
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/28202511/amplification-of-egfr-wild-type-alleles-in-non-small-cell-lung-cancer-cells-confers-acquired-resistance-to-mutation-selective-egfr-tyrosine-kinase-inhibitors
#6
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/28198176/what-is-changing-in-the-surgical-treatment-of-gastrointestinal-stromal-tumors-after-multidisciplinary-approach-a-comprehensive-literature-s-review
#7
Belinda De Simone, Luca Ansaloni, Massimo Sartelli, Federico Coccolini, Salomone Di Saverio, Maria A Pantaleo, Maristella Saponara, Margherita Nannini, Harishine K Abongwa, Josephine A Napoli, Fausto Catena
INTRODUCTION: GIST represent the most common mesenchymal neoplasms of the gastrointestinal tract Surgery is the only curative treatment for GIST. The aim of our review is to highlight the changes in the surgical treatment of GIST after the introduction of TKI therapy in a multimodality management ( neo-adiuvant or adiuvant setting). EVIDENCE ACQUISITION: We carried out a review of the recent literature about surgical treatment of GIST according to its anatomical location and size according to PRISMA STATEMENT to systematic review...
February 14, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28191799/switch-maintenance-tyrosine-kinase-inhibitors-in-egfr-mutation-positive-metastatic-non-squamous-nsclc-experience-from-the-real-world
#8
Ayinash Pandey, V Noronha, A Joshi, K Prabhash
BACKGROUND: Induction pemetrexed platin doublet is the standard of care in locally advanced and metastatic non squamous NSCLC. Maintenance TKI has been successfully explored to sustain benefit achieved after induction therapy especially in EGFR mutation positive NSCLC. The aim of this study is to evaluate outcomes with maintenance TKI in EGFR mutation positive metastatic non squamous NSCLC after induction pemetrexed-platin doublet. The objective is to calculate progression freesurvival rate, overall survival rate and factors affecting outcomes...
September 2016: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28188446/treatment-options-for-egfr-t790m-negative-egfr-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer
#9
Salvatore Corallo, Ettore D'Argento, Antonia Strippoli, Michele Basso, Santa Monterisi, Sabrina Rossi, Alessandra Cassano, Carlo M Barone
The introduction of first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib and afatinib) for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) has dramatically improved patients' prognosis and quality of life (QoL). Unfortunately, after an initial and sometimes durable benefit from EGFR-TKI therapy, all patients with EGFR-mutant lung cancer eventually become resistant to the treatment and experience disease progression. In approximately 50% of these patients, genomic alterations in the EGFR kinase domain resulting in the mutant T790M are responsible for the resistance and this has led to the development of novel EGFR inhibitors active against mutant-T790M EGFR...
February 10, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28186983/differentiation-status-of-primary-chronic-myeloid-leukemia-cells-affects-sensitivity-to-bcr-abl1-inhibitors
#10
Paavo O Pietarinen, Christopher A Eide, Pilar Ayuda-Durán, Swapnil Potdar, Heikki Kuusanmäki, Emma I Andersson, John P Mpindi, Tea Pemovska, Mika Kontro, Caroline A Heckman, Olli Kallioniemi, Krister Wennerberg, Henrik Hjorth-Hansen, Brian J Druker, Jorrit M Enserink, Jeffrey W Tyner, Satu Mustjoki, Kimmo Porkka
Tyrosine kinase inhibitors (TKI) are the mainstay treatment of BCR-ABL1-positive leukemia and virtually all patients with chronic myeloid leukemia in chronic phase (CP CML) respond to TKI therapy. However, there is limited information on the cellular mechanisms of response and particularly on the effect of cell differentiation state to TKI sensitivity in vivo and ex vivo/in vitro. We used multiple, independent high-throughput drug sensitivity and resistance testing platforms that collectively evaluated 295 oncology compounds to characterize ex vivo drug response profiles of primary cells freshly collected from newly-diagnosed patients with BCR-ABL1-positive leukemia (n = 40) and healthy controls (n = 12)...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185914/therapeutic-strategies-and-mechanisms-of-drug-resistance-in-anaplastic-lymphoma-kinase-alk-rearranged-lung-cancer
#11
REVIEW
Ryohei Katayama
Anaplastic lymphoma kinase (ALK) gene encoding the receptor tyrosine kinase ALK is expressed as a fusion gene in a variety of carcinomas. The expression of ALK is nearly undetectable in adults, and its activation is normally regulated by its ligands, FAM150A/B. However, ALK gene rearrangements result in different ALK fusion proteins that are constitutively expressed via the active promoter of fusion partner genes. ALK fusion proteins dimerize in a ligand-independent manner and lead to the dysregulation of cell proliferation via abnormal constitutive activation of ALK tyrosine kinase...
February 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28185061/a-regional-analysis-of-epidermal-growth-factor-receptor-egfr-mutated-lung-cancer-for-hse-south
#12
D Kelly, L Mc Sorley, E O'Shea, E Mc Carthy, S Bowe, C Brady, J Sui, M A Dawod, O O'Brien, D Graham, J McCarthy, L Burke, D Power, S O'Reilly, R M Bambury, D O Mahony
BACKGROUND: EGFR mutated lung cancer represents a subgroup with distinct clinical presentations, prognosis, and management requirements. We investigated the survival, prognostic factors, and real-world treatment of NSCLC patients with EGFR mutation in clinical practice. METHODS: A retrospective review of all specimens sent for EGFR analysis from December 2009 to September 2015 was performed. Patient demographics, specimen type, EGFR mutation status/type, stage at diagnosis, treatment, response rate, and survival data were recorded...
February 9, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28184964/absorption-metabolism-and-excretion-of-14-c-ponatinib-after-a-single-oral-dose-in-humans
#13
Yihua E Ye, Caroline N Woodward, Narayana I Narasimhan
PURPOSE: Ponatinib is a novel tyrosine kinase inhibitor (TKI) specifically designed to inhibit native and mutated BCR-ABL. In the United States, ponatinib has received accelerated approval for adults with T315I-positive chronic myeloid leukemia (CML) or T315I (gatekeeper mutation)-positive, Philadelphia chromosome-positive, acute lymphoblastic leukemia (Ph + ALL), and patients with CML or Ph + ALL for whom no other TKI therapy is indicated. The objective of this phase 1, mass balance study was to evaluate the absorption, metabolism, and excretion of [(14)C]ponatinib in healthy subjects...
February 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28184913/determining-egfr-tki-sensitivity-of-g719x-and-other-uncommon-egfr-mutations-in-non-small-cell-lung-cancer-perplexity-and-solution-review
#14
Kaidi Li, Maojun Yang, Naixin Liang, Shanqing Li
Mutations in epidermal growth factor receptor (EGFR) play critical roles in the pathogenesis of non-small cell lung cancer (NSCLC), and they are highly associated with sensitivity to tyrosine kinase inhibitors (TKIs). While the pathogenic and pharmacological characteristics of common mutations in EGFR have been thoroughly investigated, those of uncommon mutations remain to be elucidated. Traditional approaches to study common mutations by randomized controlled trials are not feasible for uncommon mutations owing to their rarity...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28183697/safety-and-antitumor-activity-of-the-multi-targeted-pan-trk-ros1-and-alk-inhibitor-entrectinib-rxdx-101-combined-results-from-two-phase-1-trials-alka-372-001-and-startrk-1
#15
Alexander Drilon, Salvatore Siena, Sai-Hong Ignatius Ou, Manish Patel, Myung Ju Ahn, Jeeyun Lee, Todd M Bauer, Anna F Farago, Jennifer J Wheler, Stephen V Liu, Robert Doebele, Laura Giannetta, Giulio Cerea, Giovanna Marrapese, Michele Schirru, Alessio Amatu, Katia Bencardino, Laura Palmeri, Andrea Sartore-Bianchi, Angelo Vanzulli, Sara Cresta, Silvia Damian, Matteo Duca, Elena Ardini, Gang Li, Jason Christiansen, Karey Kowalski, Ann Johnson, Rupal Patel, David Luo, Edna Chow-Maneval, Zachary Hornby, Pratik S Multani, Alice T Shaw, Filippo G De Braud
Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two Phase 1 studies in patients with advanced or metastatic solid tumors, including patients with active CNS disease. Here we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the RP2D...
February 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28178685/overwhelming-rapid-metabolic-and-structural-response-to-apatinib-in-radioiodine-refractory-differentiated-thyroid-cancer
#16
Yansong Lin, Chen Wang, Wen Gao, Ruixue Cui, Jun Liang
Currently, patients with radioiodine refractory differentiated thyroid cancer (RAIR-DTC) have limited treatment options. In this study, we aimed to assess the short-term efficacy and safety of apatinib in RAIR-DTC. Ten adult patients were prospectively enrolled to receive oral apatinib (750 mg q.d). The primary endpoints were change in serum thyroglobulin (Tg) concentration, disease control rate (DCR) and objective response rate (ORR) based on RECIST 1.1 criteria. The secondary endpoints included change in glucose metabolism, evaluated by maximum standard uptake value (SUVmax), and safety...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178168/rapid-intracranial-response-to-osimertinib-without-radiotherapy-in-nonsmall-cell-lung-cancer-patients-harboring-the-egfr-t790m-mutation-two-case-reports
#17
Taro Koba, Takashi Kijima, Takayuki Takimoto, Haruhiko Hirata, Yujiro Naito, Masanari Hamaguchi, Tomoyuki Otsuka, Muneyoshi Kuroyama, Izumi Nagatomo, Yoshito Takeda, Hiroshi Kida, Atsushi Kumanogoh
RATIONALE: Most of nonsmall cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) activating mutations eventually acquire resistance to the first EGFR-tyrosine kinase inhibitors (TKIs) therapy after varying periods of treatment. Of note, approximately one-third of those patients develop brain metastases, which deteriorate their quality of life and survival. The effect of systemic chemotherapy on brain metastases after acquisition of EGFR-TKI resistance is limited, and thus far, whole-brain radiation therapy, which may cause the harmful effect on neurocognitive functions, has been the only established therapeutic option for especially symptomatic brain metastases...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28174389/-molecular-biology-for-surgical-treatment-of-lung-cancer
#18
Kenichi Suda, Tetsuya Mitsudomi
Progress in lung cancer research achieved during the last 10 years was summarized. These include identification of novel driver mutations and application of targeted therapies, resistance mechanisms to targeted therapies, and immunotherapy with immune checkpoint inhibitors. Molecular biology also affects the field of surgical treatment. Several molecular markers have been reported to predict benign/ malignant or stable/growing tumors, although far from clinical application. In perioperative period, there is a possibility of atrial natriuretic peptide to prevent cancer metastasis...
January 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28169304/targeted-therapies-remembrance-of-things-past-discontinuation-of-second-generation-tki-therapy-for-cml
#19
Timothy P Hughes, David M Ross
No abstract text is available yet for this article.
February 7, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28167215/treatments-for-egfr-mutant-non-small-cell-lung-cancer-nsclc-the-road-to-a-success-paved-with-failures
#20
REVIEW
Dae Ho Lee
The discovery of epidermal growth factor receptor (EGFR) activating mutations in non-small cell lung cancer (NSCLC) and the success story of EGFR tyrosine kinases inhibitors (TKIs) has changed the paradigm of cancer therapy from empirical cytotoxic chemotherapy to molecular-targeted cancer therapy. As a result, EGFR TKI therapy, including gefitinib, erlotinib and afatinib, has become the standard therapy for NSCLC patients with EGFR activating mutation as first-line therapy. However, most patients inevitably progress despite initial dramatic and rapid response to EGFR TKIs and therefore during the last decade, a lot of efforts have been made to identify and overcome various resistance mechanisms...
February 3, 2017: Pharmacology & Therapeutics
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