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Crizotinib

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https://www.readbyqxmd.com/read/28821506/crizotinib-has-antitumor-activity-in-alk-positive-alcl-and-imt
#1
(no author information available yet)
Crizotinib has an overall response rate of 90% in ALCL and 86% in IMT at the recommended phase II dose.
August 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28819999/high-glucose-induces-hgf-independent-activation-of-met-receptor-in-human-renal-tubular-epithelium
#2
Lucia Mesarosova, Peter Ochodnicky, Jaklien C Leemans, Sandrine Florquin, Peter Krenek, Jan Klimas
CONTEXT: The role of hepatocyte growth factor (HGF) in diabetic kidney damage remains controversial. OBJECTIVE: To test the hypothesis that high glucose levels activate pathways related to HGF and its receptor Met and that this could participate in glucose-induced renal cell damage. MATERIALS AND METHODS: HK2 cells, a human proximal tubule epithelial cell line, were stimulated with high glucose for 48 hours. Levels of pMet/Met, pEGFR/EGFR, pSTAT3/STAT3, pAkt/Akt and pERK1/2/ERK1/2 were studied by immunoblotting...
August 18, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28818606/recent-advances-in-targeting-ros1-in-lung-cancer
#3
REVIEW
Jessica J Lin, Alice T Shaw
ROS1 is a validated therapeutic target in non-small cell lung cancer (NSCLC). In a phase I study, the multi-targeted MET/ALK/ROS1 inhibitor crizotinib demonstrated remarkable efficacy in ROS1-rearranged NSCLCs, and consequently gained approval by the United States Food and Drug Administration as well as the European Medicines Agency in 2016. However, similar to other oncogene-driven lung cancers, ROS1-rearranged lung cancers treated with crizotinib eventually acquire resistance, leading to disease relapse. Novel ROS1 inhibitors and therapeutic strategies are therefore needed...
August 14, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28808224/off-label-use-of-crizotinib-as-a-neoadjuvant-treatment-for-a-young-patient-when-conventional-chemotherapy-gave-no-benefits-in-stage-iiia-non-small-cell-lung-cancer
#4
Delphine Dumont, Pascal Dô, Delphine Lerouge, Gaëtane Planchard, Marc Riffet, Catherine Dubos-Arvis, Serge Danhier, Radj Gervais
BACKGROUND The treatment of locally advanced non-small cell lung cancer involves a combination of chemotherapy, surgery, and radiotherapy. Each case is discussed and the best strategy is chosen individually, following international guidelines. CASE REPORT A 37-year-old man was diagnosed with locally advanced broncho-pulmonary adenocarcinoma (stage IIIA). The disease was stable after 2 cycles of cisplatin plus Navelbine used as neoadjuvant therapy. FISH analysis revealed an ALK rearrangement. The patient then received unlicensed crizotinib as second-line neoadjuvant treatment, which led to an almost complete radiological and metabolic response...
August 15, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28806950/precision-medicine-approaches-to-lung-adenocarcinoma-with-concomitant-met-and-her2-amplification
#5
Doo-Yi Oh, Kyungsoo Jung, Ji-Young Song, Seokhwi Kim, Sang Shin, Yong-Jun Kwon, Ensel Oh, Woong-Yang Park, Sang Yong Song, Yoon-La Choi
BACKGROUND: Patient-derived xenograft (PDX) models are important tools in precision medicine and for the development of targeted therapies to treat cancer patients. This study aimed to evaluate our precision medicine strategy that integrates genomic profiling and preclinical drug-screening platforms, in order to personalize cancer treatments using PDX models. METHODS: We performed array-comparative genomic hybridization, microarray, and targeted next-generation sequencing analyses, in order to determine the oncogenic driver mutations...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28806414/alpha-tocopherol-attenuates-the-anti-tumor-activity-of-crizotinib-against-cells-transformed-by-npm-alk
#6
Yuki Uchihara, Fumihito Ueda, Kenji Tago, Yosuke Nakazawa, Tomoyuki Ohe, Tadahiko Mashino, Shigenobu Yokota, Tadashi Kasahara, Hiroomi Tamura, Megumi Funakoshi-Tago
Anaplastic large cell lymphomas (ALCL) are mainly characterized by harboring the fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). The ALK inhibitor, crizotinib specifically induced apoptosis in Ba/F3 cells expressing NPM-ALK by inhibiting the activation of NPM-ALK and its downstream molecule, signal transducer and activator of transcription factor 3 (STAT3). We found that α-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties...
2017: PloS One
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#7
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28802669/studies-on-the-dynamic-resolution-of-crizotinib-intermediate
#8
Alexandre da S de França, Marcus V M Silva, Rebeca V Neves, Stefania P de Souza, Raquel A C Leão, Carlos M Monteiro, Ângelo Rocha, Carlos A M Afonso, Rodrigo O M A de Souza
Crizotinib is an anti-cancer agent approved for treatment of non-small cell lung carcinoma. Retrosynthetic analysis revels 1-(2,6-dichloro-3-fluorophenyl)ethanol as an important intermediate, which can be made available by different biocatalytic approaches. Herein we report our results on the kinetic and dynamic resolution towards the desired chiral intermediate for Crizotinib synthesis. The results obtained show that very good conversions and high selectivity could be obtained for the kinetic resolution (45% conv...
July 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28794366/regression-of-crizotinib-associated-complex-cystic-lesions-after-switching-to-alectinib
#9
Kageaki Taima, Hisashi Tanaka, Yoshihito Tanaka, Masamichi Itoga, Shingo Takanashi, Sadatomo Tasaka
Crizotinib, which is effective in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer, is sometimes associated with the generation of complex renal cysts. A 56-year-old man with ALK positive adenocarcinoma received crizotinib. Ten months after the introduction of crizotinib, a cystic lesion developed from his right kidney to the iliopsoas muscle, accompanied by fever, anemia, and hypoproteinemia. After 17 months of treatment, crizotinib was switched to alectinib, followed by the recovery of hypoproteinemia and systemic inflammation...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28781805/successful-oral-desensitization-with-crizotinib-after-crizotinib-induced-hepatitis-in-an-anaplastic-lymphoma-kinase-rearranged-non-small-cell-lung-cancer-patient-a-case-report
#10
Yuto Yasuda, Yasuyo Nishikawa, Yuichi Sakamori, Makoto Terao, Kentaro Hashimoto, Tomoko Funazo, Takashi Nomizo, Takahiro Tsuji, Hironori Yoshida, Hiroki Nagai, Hiroaki Ozasa, Toyohiro Hirai, Young Hak Kim
Crizotinib is one of the molecularly-targeted agents targeted against anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Although its effects appear to be promising, crizotinib may cause adverse effects in patients with ALK-rearranged NSCLC. Hepatic laboratory abnormalities are frequently observed with crizotinib and treatment discontinuation is occasionally required. We herein report the case of a 51-year-old woman diagnosed with relapsed ALK-rearranged NSCLC, who received crizotinib as second-line systemic chemotherapy...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28781781/responses-to-crizotinib-and-chemotherapy-in-patients-with-lung-adenocarcinoma-harboring-a-concomitant-egfr-mutation-and-alk-gene-rearrangement-a-case-report-and-review-of-the-literature
#11
Yuping Li, Shanshan Su, Guoping Cai, Quan Lin, Ying Zhou, Jinsheng Ouyang, Bicheng Chen, Junru Ye, Xiuling Wu, Chengshui Chen
Previous studies have indicated that, in lung cancers, the gene rearrangement of ALK is mutually exclusive with mutations in the epidermal growth factor receptor (EGFR) gene. However, the coexistence of EML4-ALK fusions and EGFR mutations (double positive) has been occasionally reported, with frequencies ranging from 0-8%. Currently, no consensus standard therapy exists for tumors with double positive mutations. In the present case report, the case is described of a 53-year-old woman with stage IV lung adenocarcinoma, harboring a concomitant EGFR mutation and ALK gene rearrangement, who was refractory to gefitinib administration but demonstrated a good response to crizotinib and pemetrexed chemotherapy...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28766541/-use-of-crizotinib-for-refractory-alk-positive-lymphomas
#12
L N Shelikhova, V V Fominykh, D S Abramov, N V Myakova, M A Maschan, A A Maschan
AIM: To evaluate the safety and efficacy of crizotinib used in pediatric patients with relapsed or refractory ALK-positive anaplastic large-cell lymphoma (ALCL). SUBJECTS AND METHODS: The paper describes the experience with crizotinib used in 8 patients with refractory ALK-ALCL before and after allogeneic hematopoietic stem cell transplantation (HSCT). RESULTS: All the 8 (100%) patients treated with crizotinib were recorded to have complete responses, including complete metabolic ones (tumor disappearance as evidenced by positron emission tomography (PET)/computed tomography...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28765324/glesatinib-exhibits-antitumor-activity-in-lung-cancer-models-and-patients-harboring-met-exon-14-mutations-and-overcomes-mutation-mediated-resistance-to-type-i-met-inhibitors-in-nonclinical-models
#13
Lars Engstrom, Ruth Aranda, Matthew Lee, Elizabeth A Tovar, Curt Essenburg, Zachary B Madaj, Harrah Chiang, David Briere, Jill Hallin, Pedro P Lopez-Casas, Natalia Banos, Camino Menéndez, Manuel Hidalgo, Vanessa Tassell, Richard Chao, Darya I Chudova, Richard B Lanman, Peter Olson, Lyudmila Bazhenova, Sandip P Patel, Carrie R Graveel, Mizuki Nishino, Geoffrey I Shapiro, Nir Peled, Mark M Awad, Pasi A Janne, James G Christensen
MET exon 14 deletion (METex14 del) mutations represent a novel class of non-small cell lung cancer (NSCLC) driver mutations.  We evaluated glesatinib, a spectrum-selective MET inhibitor exhibiting a type II binding mode, in METex14 del-positive nonclinical models and NSCLC patients and assessed its ability to overcome resistance to type I MET Inhibitors.<br /><br />Experimental Design: As most MET inhibitors in clinical development bind the active site with a type I binding mode, we investigated mechanisms of acquired resistance to each MET inhibitor class utilizing in vitro and in vivo models and in glesatinib clinical trials...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28748401/system-biology-approach-to-identify-potential-receptor-for-targeting-cancer-and-biomolecular-interaction-studies-of-indole-2-1-a-isoquinoline-derivative-as-anticancerous-drug-candidate-against-it
#14
Devender Arora, Ritu Chaudhary, Ajeet Singh
Cancer is a public health concern which is spreading throughout the world. Different approaches have been employed to combat this disease. System biology approach has been used to understand the molecular mechanisms of drugs targeting cancer cell's receptor which have opened-up a window to develop effective drugs for it. We have demonstrated biomolecular interaction studies using the rational drug design of indole[2,1-a]isoquinoline derivative as a potent inhibitor against identified cancerous protein PIK3CA -a catalytic sub-unit of PI3K family protein-and compared its affinity with FDA approved drugs for receptors such as dactolisib, idelalisib, and several others such afatinib, avastin, ceritinib and crizotinib, etc...
July 26, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28740365/spotlight-on-ceritinib-in-the-treatment-of-alk-nsclc-design-development-and-place-in-therapy
#15
REVIEW
Mariacarmela Santarpia, Maria Grazia Daffinà, Alessandro D'Aveni, Grazia Marabello, Alessia Liguori, Elisa Giovannetti, Niki Karachaliou, Maria Gonzalez Cao, Rafael Rosell, Giuseppe Altavilla
The identification of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer (NSCLC) has radically changed the treatment of a subset of patients harboring this oncogenic driver. Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for advanced, ALK-positive NSCLC patients. However, despite crizotinib's efficacy, patients almost invariably progress, with the central nervous system being one of the most common sites of relapse...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28731868/inflammatory-myofibroblastic-tumors-of-the-female-genital-tract-are-under-recognized-a-low-threshold-for-alk-immunohistochemistry-is-required
#16
Justine L Pickett, Angela Chou, Juliana A Andrici, Adele Clarkson, Loretta Sioson, Amy Sheen, Jessica Reagh, Fedaa Najdawi, Yoomee Kim, Denise Riley, Jayne Maidens, David Nevell, Kirsten McIlroy, Susan Valmadre, Greg Gard, Russell Hogg, John Turchini, Gregory Robertson, Michael Friedlander, Anthony J Gill
Inflammatory myofibroblastic tumor (IMT) of the female genital tract is under-recognized. We investigated the prevalence of ALK-positive IMT in lesions previously diagnosed as gynecologic smooth muscle tumors. Immunohistochemistry (IHC) for ALK was performed on tissue microarrays of unselected tumors resected from 2009 to 2013. Three of 1176 (0.26%) "leiomyomas" and 1 of 44 (2.3%) "leiomyosarcomas" were ALK IHC positive, confirmed translocated by fluorescence in situ hybridization (FISH) and therefore more appropriately classified as IMT...
July 20, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28730760/targeted-therapy-with-anaplastic-lymphoma-kinase-inhibitors-in-non-small-cell-lung-cancer-even-with-brain-metastasis
#17
Bekir Muhammet Hacioglu, Osman Kostek, Bulent Erdogan, Sernaz Uzunoglu, Irfan Cicin
The incidence of brain metastases has increased as a result of improved systemic disease control and advances in imaging. Brain metastasis can occur approximately in 25-40% of the patients with non-small cell lung cancer (NSCLC) and it is a frequent cause of death. Stereotactic radiosurgery, whole-brain radiotherapy (WBRT) or surgical resection are the local treatment modalities for brain metastases which are feasible either alone, in combination, or as sequential treatments. Resistance to systemic therapy for brain metastasis poses significant clinical problems...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28729021/ascend-8-a-randomized-phase-1-study-of-ceritinib-450-mg-or-600-mg-taken-with-a-low-fat-meal-versus-750-mg-in-fasted-state-in-patients-with-anaplastic-lymphoma-kinase-alk-rearranged-metastatic-non-small-cell-lung-cancer-nsclc
#18
Byoung Chul Cho, Dong-Wan Kim, Alessandra Bearz, Scott A Laurie, Mark McKeage, Gloria Borra, Keunchil Park, Sang-We Kim, Marwan Ghosn, Andrea Ardizzoni, Evaristo Maiello, Alastair Greystoke, Richard Yu, Karen Osborne, Wen Gu, Jeffrey W Scott, Vanessa Q Passos, Yvonne Y Lau, Anna Wrona
INTRODUCTION: Ceritinib 750 mg fasted is approved for treatment of anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients previously treated with crizotinib. Part 1 of ASCEND-8 study determined whether administering ceritinib 450 mg or 600 mg with a low-fat meal may enhance gastrointestinal (GI) tolerability vs 750 mg fasted in ALK+ NSCLC patients while maintaining similar exposure. METHODS: ASCEND-8 is a multicenter, randomized, open-label, phase 1 study...
July 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28721071/adverse-renal-effects-of-anaplastic-lymphoma-kinase-inhibitors-and-the-response-to-alectinib-of-an-alk-lung-cancer-patient-with-renal-dysfunction
#19
Midori Shimada, Minoru Fukuda, Masaaki Fukuda, Takeshi Kitazaki, Kohji Hashiguchi, Takaya Ikeda, Hiroyuki Yamaguchi, Katsumi Nakatomi, Kazuto Ashizawa, Hiroshi Mukae
A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK) gene translocation was identified, the therapy was changed to crizotinib. However, the patient's blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28721068/patients-harboring-alk-rearrangement-adenocarcinoma-after-acquired-resistance-to-crizotinib-and-transformation-to-small-cell-lung-cancer-a-case-report
#20
You-Cai Zhu, Xing-Hui Liao, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Li-Hua Zhong, Kai-Qi Du, Yan-Ping Chen, Gang Chen, Mei-Yu Fang
Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression...
2017: OncoTargets and Therapy
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