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Crizotinib

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https://www.readbyqxmd.com/read/28646771/efficacy-of-alectinib-in-central-nervous-system-metastases-in-crizotinib-resistant-alk-positive-non-small-cell-lung-cancer-comparison-of-recist-1-1-and-rano-hgg-criteria
#1
Leena Gandhi, Sai-Hong Ignatius Ou, Alice T Shaw, Fabrice Barlesi, Anne-Marie C Dingemans, Dong-Wan Kim, D Ross Camidge, Brett G M Hughes, James C-H Yang, Javier de Castro, Lucio Crino, Hervé Léna, Pascal Do, Sophie Golding, Walter Bordogna, Ali Zeaiter, Ahmed Kotb, Shirish Gadgeel
BACKGROUND: Central nervous system (CNS) progression is common in patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) receiving crizotinib. Next-generation ALK inhibitors have shown activity against CNS metastases, but accurate assessment of response and progression is vital. Data from two phase II studies in crizotinib-refractory ALK+ NSCLC were pooled to examine the CNS efficacy of alectinib, a CNS-active ALK inhibitor, using Response Evaluation Criteria in Solid Tumours (RECIST version 1...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28638122/synergistic-effects-of-various-her-inhibitors-in-combination-with-igf-1r-c-met-and-src-targeting-agents-in-breast-cancer-cell-lines
#2
Aryan Stanley, G Hossein Ashrafi, Alan M Seddon, Helmout Modjtahedi
Overexpression of HER2 has been reported in around 25% of human breast cancers. Despite recent advances in HER2 targeted therapy, many patients still experience primary and secondary resistance to such treatments, the mechanisms for which are poorly understood. Here, we investigated the sensitivity of a panel of breast cancer cell lines to treatment with various types of HER-family inhibitors alone or in combination with other tyrosine kinase inhibitors or chemotherapeutic agents. We found that treatment with the second-generation irreversible HER-family inhibitors, particularly afatinib and neratinib, were more effective than treatment with the first-generation reversible inhibitors in inhibiting growth, migration and downstream cell signalling in breast cancer cells...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637004/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#3
Rebecca D Schroeder, Woonyoung Choi, David S Hong, David J McConkey
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636982/meta-analysis-of-incidence-and-risk-of-severe-adverse-events-and-fatal-adverse-events-with-crizotinib-monotherapy-in-patients-with-alk-positive-nsclc
#4
Qian Zhu, Hao Hu, Feng Jiang, Chang Ying Guo, Xiong Wen Yang, Xi Liu, Yu Kang Kuang
BACKGROUND: Numerous clinical trials show crizotinib has promising efficacy for anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients which trigger the substitution of traditional chemotherapy to be the current standard first-line treatment for these patients. Conversely, few reports systematically analyze toxicity of crizotinib. Hence, we performed a first meta-analysis to determine the risk of crizotinib-related severe adverse events (SAEs) and fatal adverse events (FAEs) in ALK positive NSCLC patients...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634201/phosphoproteomic-profiling-reveals-alk-and-met-as-novel-actionable-targets-across-synovial-sarcoma-subtypes
#5
Emmy D G Fleuren, Myrella Vlenterie, Winette van der Graaf, Melissa H S Hillebrandt-Roeffen, James Blackburn, Xiuquan Ma, Howard Chan, Mandy C Magias, Anke van Erp, Laurens van Houdt, Sabri Cebeci, Amy van de Ven, Uta E Flucke, Erin E Heyer, David M Thomas, Christopher J Lord, Kieren D Marini, Vijesh Vaghjiani, Tim Mercer, Jason E Cain, Jianmin Wu, Yvonne M H Versleijen-Jonkers, Roger J Daly
Despite intensive multi-modal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical success, urging an unbiased and comprehensive analysis of oncogenic signaling networks to reveal therapeutic targets and personalized treatment strategies. Here we applied mass spectrometry-based phosphoproteomic profiling to the largest and most heterogeneous set of sarcoma cell lines characterized to date and identified novel tyrosine phosphorylation patterns, enhanced tyrosine kinases in specific subtypes, and potential driver kinases...
June 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28629461/cost-effectiveness-of-lung-cancer-screening-and-treatment-methods-a-systematic-review-of-systematic-reviews
#6
Farbod Ebadifard Azar, Saber Azami-Aghdash, Fatemeh Pournaghi-Azar, Alireza Mazdaki, Aziz Rezapour, Parvin Ebrahimi, Negar Yousefzadeh
BACKGROUND: Due to extensive literature in the field of lung cancer and their heterogeneous results, the aim of this study was to systematically review of systematic reviews studies which reviewed the cost-effectiveness of various lung cancer screening and treatment methods. METHODS: In this systematic review of systematic reviews study, required data were collected searching the following key words which selected from Mesh: "lung cancer", "lung oncology", "lung Carcinoma", "lung neoplasm", "lung tumors", "cost- effectiveness", "systematic review" and "Meta-analysis"...
June 19, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28628492/complete-remission-of-intrathecal-metastases-with-lorlatinib-therapy-in-a-heavily-pretreated-alk-positive-lung-cancer-patient
#7
Maximilian J Hochmair, Sophia Schwab, Helmut Prosch
Patients with lung cancer who show EML4-ALK translocation are routinely treated with ALK tyrosine kinase inhibitors, although in the majority of cases, these patients develop resistance over time. The central nervous system is a common of site of recurrence in this population, which calls for next-generation drugs that can penetrate into the brain and achieve clinically meaningful central nervous system activity. Here, I report the case of a female patient diagnosed with adenocarcinoma of the lung in 2005, at the age of 46 years, who underwent lobectomy and then experienced a series of progression episodes 6 years later...
June 16, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28626524/-19-f-nmr-based-dual-site-reporter-assay-for-the-discovery-and-distinction-of-catalytic-and-allosteric-kinase-inhibitors
#8
Lukasz Skora, Wolfgang Jahnke
In modern kinase drug discovery, allosteric inhibitors have become a focus of attention due to their potential selectivity, but such compounds are difficult to identify. Here we describe an NMR-based competition assay using (19)F-containing reporter molecules, which allows for rapid identification and discrimination between ATP-competitive and allosteric kinase inhibitors. We illustrate the principle of such a dual-site competition assay with the example of catalytic and allosteric ABL1 kinase inhibitors. The assay can also be used to identify and characterize mixed binding modes of well-known drugs, as shown for crizotinib and fingolimod...
June 8, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28625556/alectinib-surpasses-crizotinib-for-untreated-alk-positive-nsclc
#9
Judith A Gilbert
No abstract text is available yet for this article.
June 15, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28622610/f1174v-mutation-alters-the-alk-active-conformation-in-response-to-crizotinib-in-nsclc-insight-from-molecular-simulations
#10
Fariba Dehghanian, Maryam Kay, Sadeq Vallian
Crizotinib is an efficient antineoplastic drug for treatment of non-small cell lung carcinoma (NSCLC), which is identified as an anaplastic lymphoma kinase (ALK) inhibitor. F1174V is a recently identified acquired point mutation relating to the Crizotinib resistance in NSCLC patients. The mechanism of Crizotinib resistance relating to F1174V mutation as a non-active site mutation remains unclear. In this study, the molecular dynamic simulation was used to investigate the possible mechanisms by which F1174V mutation may affect the structure and activity of ALK kinase domain...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28617069/simultaneous-determination-of-six-tyrosine-kinase-inhibitors-in-human-plasma-using-hplc-q-orbitrap-mass-spectrometry
#11
Mao-Wei Ni, Jie Zhou, Hui Li, Wei Chen, Han-Zhou Mou, Zhi-Guo Zheng
AIM: Gefitinib, erlotinib, icotinib, crizotinib, lapatinib and apatinib are targeted cancer therapy agents acting through inhibition of tyrosine kinase. Method for quantifying these six drugs in human plasma of patients was required. MATERIALS & METHODS: An HPLC-Q-Orbitrap method (based on HPLC-MS/MS) was developed and validated for the simultaneous detection and quantitation of six tyrosine kinase inhibitors in human plasma. Sample was extracted by liquid-liquid extraction (ethyl acetate: tert-Butyl methyl ether, 1:1 v/v)...
June 15, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28611010/cases-of-alk-rearranged-lung-cancer-with-5-year-progression-free-survival-with-crizotinib-as-initial-precision-therapy
#12
Deepa Rangachari, Xiuning Le, Meghan Shea, Mark S Huberman, Paul A VanderLaan, Susumu S Kobayashi, Daniel B Costa
No abstract text is available yet for this article.
June 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28607809/rapid-response-of-brain-metastasis-to-crizotinib-in-a-patient-with-klc1-alk-fusion-and-met-gene-amplification-positive-non-small-cell-lung-cancer-a-case-report
#13
Peng Wang, Pei Xiao, Yingnan Ye, Pengpeng Liu, Lei Han, Li Dong, Chunhua She, Jinpu Yu
Non-small cell lung cancer (NSCLC) ranks as the leading cause of cancer-related death in the world. Brain metastasis (BM) is a common complication of NSCLC, with 25%-40% of patients developing BM during the course of the disease. A significant strategy of local disease control in the central nervous system is radiation therapy. With the development of precision medicine, the concept of treating lung cancer BM has gradually changed. In this case, we performed a surgical procedure to obtain enough tumor tissue for the detection of the target gene and other related experiments after the patient was informed...
May 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28606126/pooled-safety-analyses-of-alk-tki-inhibitor-in-alk-positive-nsclc
#14
Qian Zhu, Hao Hu, De-Sheng Weng, Xiao-Fei Zhang, Chang-Long Chen, Zi-Qi Zhou, Yan Tang, Jian-Chuan Xia
BACKGROUND: The anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have been administered to patients with ALK-positive non-small cell lung cancer for a long period of time and show a promising response. However, the differences in the toxicity profiles among these drugs are still unclear. METHODS: We performed a comprehensive search of the MEDLINE, EMBASE, WEB OF SCIENCE and COCHRANE databases from the drugs' inception to May 2016 to identify clinical trials...
June 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28602779/ceritinib-versus-chemotherapy-in-patients-with-alk-rearranged-non-small-cell-lung-cancer-previously-given-chemotherapy-and-crizotinib-ascend-5-a-randomised-controlled-open-label-phase-3-trial
#15
Alice T Shaw, Tae Min Kim, Lucio Crinò, Cesare Gridelli, Katsuyuki Kiura, Geoffrey Liu, Silvia Novello, Alessandra Bearz, Oliver Gautschi, Tony Mok, Makoto Nishio, Giorgio Scagliotti, David R Spigel, Stéphanie Deudon, Cheng Zheng, Serafino Pantano, Patrick Urban, Cristian Massacesi, Kalyanee Viraswami-Appanna, Enriqueta Felip
BACKGROUND: Ceritinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor, which has shown robust anti-tumour efficacy, along with intracranial activity, in patients with ALK-rearranged non-small-cell lung cancer. In phase 1 and 2 studies, ceritinib has been shown to be highly active in both ALK inhibitor-naive and ALK inhibitor-pretreated patients who had progressed after chemotherapy (mostly multiple lines). In this study, we compared the efficacy and safety of ceritinib versus single-agent chemotherapy in patients with advanced ALK-rearranged non-small-cell lung cancer who had previously progressed following crizotinib and platinum-based doublet chemotherapy...
June 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28601386/detection-of-alk-and-kras-mutations-in-circulating-tumor-dna-of-patients-with-advanced-alk-positive-nsclc-with-disease-progression-during-crizotinib-treatment
#16
Paola Bordi, Marcello Tiseo, Eleonora Rofi, Iacopo Petrini, Giuliana Restante, Romano Danesi, Marzia Del Re
BACKGROUND: In patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), disease progression occurs after a median of 9 to 10 months of crizotinib treatment. Several mechanisms of resistance have been identified and include ALK mutations and amplification or the activation of bypassing signaling pathways. Rebiopsy in NSCLC patients represents a critical issue and the analysis of circulating cell-free DNA (cfDNA) has a promising role for the identification of resistance mechanisms...
May 18, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28600466/alectinib-superior-to-crizotinib-for-alk-nsclc
#17
(no author information available yet)
Findings from the global phase III ALEX trial unequivocally show that alectinib is superior to crizotinib as first-line therapy for ALK+ non-small cell lung cancer. Alectinib more than doubled progression-free survival, significantly reduced the incidence of brain and CNS metastases, and should be considered the new standard of care.
June 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28599617/insight-into-the-key-features-for-ligand-binding-in-y1230-mutated-c-met-kinase-domain-by-molecular-dynamics-simulations
#18
Libo Yan, Li Zhang, Yanmin Zhang, Xin Qiao, Jing Pan, Haichun Liu, Shuai Lu, Bingren Xiang, Tao Lu, Haoliang Yuan
c-Met kinase has been considered as an attractive target for developing antitumor agents. The strong interactions between Tyr1230 and the inhibitors emphasized its importance for ligand binding. The clinically related Tyr1230 mutations have made negative impacts on current c-Met kinase inhibitors, especially the exquisitely selective ones, like PF-04217903, while the multi-targeted inhibitors, like Crizotinib, were not affected so much. In this study, the protein-ligand interactions between c-Met kinase domain (wild, Y1230C and Y1230H) and these inhibitors were compared...
June 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28599410/resistance-to-nanoparticle-albumin-bound-paclitaxel-is-mediated-by-abcb1-in-urothelial-cancer-cells
#19
Stefan Vallo, Raoul Köpp, Martin Michaelis, Florian Rothweiler, Georg Bartsch, Maximilian P Brandt, Kilian M Gust, Felix Wezel, Roman A Blaheta, Axel Haferkamp, Jindrich Cinatl
Nanoparticle albumin-bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro-apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5'-triphosphate-binding cassette transporter subfamily B, member 1 (ABCB1)...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28597393/brigatinib-first-global-approval
#20
Anthony Markham
Brigatinib (ALUNBRIG™) is a small molecule antineoplastic anaplastic lymphoma kinase (ALK) inhibitor being developed by ARIAD Pharmaceuticals (a wholly-owned subsidiary of Takeda Pharmaceutical Company). In April 2017 brigatinib received accelerated approval in the USA for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. The development of resistance to crizotinib is a therapeutic challenge that has led to the development of second-generation ALK-inhibitors such as brigatinib, which have activity against treatment-resistant ALK mutants...
June 8, 2017: Drugs
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