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https://www.readbyqxmd.com/read/29782561/lorlatinib-in-alk-and-ros1-positive-nsclc-the-future-has-a-start
#1
EDITORIAL
Francesco Facchinetti, Luc Friboulet
No abstract text is available yet for this article.
April 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29774128/systematic-review-and-meta-analysis-of-selected-toxicities-of-approved-alk-inhibitors-in-metastatic-non-small-cell-lung-cancer
#2
Rubens Barros Costa, Ricardo L B Costa, Sarah M Talamantes, Jason B Kaplan, Manali A Bhave, Alfred Rademaker, Corinne Miller, Benedito A Carneiro, Devalingam Mahalingam, Young Kwang Chae
Introduction: Anaplastic lymphoma kinase ( ALK ) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. Materials and Methods: A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755669/a-stitch-in-time-saves-nine-external-quality-assessment-rounds-demonstrate-improved-quality-of-biomarker-analysis-in-lung-cancer
#3
Cleo Keppens, Véronique Tack, Nils 't Hart, Lien Tembuyser, Ales Ryska, Patrick Pauwels, Karen Zwaenepoel, Ed Schuuring, Florian Cabillic, Luigi Tornillo, Arne Warth, Wilko Weichert, Elisabeth Dequeker
Biomarker analysis has become routine practice in the treatment of non-small cell lung cancer (NSCLC). To ensure high quality testing, participation to external quality assessment (EQA) schemes is essential. This article provides a longitudinal overview of the EQA performance for EGFR , ALK , and ROS1 analyses in NSCLC between 2012 and 2015. The four scheme years were organized by the European Society of Pathology according to the ISO 17043 standard. Participants were asked to analyze the provided tissue using their routine procedures...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29744867/p-glycoprotein-mdr1-abcb1-restricts-brain-accumulation-and-cytochrome-p450-3a-cyp3a-limits-oral-availability-of-the-novel-alk-ros1-inhibitor-lorlatinib
#4
Wenlong Li, Rolf W Sparidans, Yaogeng Wang, Maria C Lebre, Els Wagenaar, Jos H Beijnen, Alfred H Schinkel
Lorlatinib (PF-06463922) is a promising oral anaplastic lymphoma kinase (ALK) and ROS1 inhibitor currently in Phase III clinical trials for treatment of non-small cell lung cancer (NSCLC) containing an ALK rearrangement. With therapy-resistant brain metastases a major concern in NSCLC, lorlatinib was designed to have high membrane and blood-brain barrier permeability. We investigated the roles of the multidrug efflux transporters ABCB1 and ABCG2, and the multispecific drug-metabolizing enzyme CYP3A in plasma pharmacokinetics and tissue distribution of lorlatinib using genetically modified mouse strains...
May 9, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29738763/3d-culture-system-containing-gellan-gum-restores-oncogene-dependence-in-ros1-rearrangements-non-small-cell-lung-cancer
#5
Bo Gong, Tomoko Oh-Hara, Naoya Fujita, Ryohei Katayama
The ROS1 fusion gene has been identified in approximately 1% of non-small cell lung cancer (NSCLC) cases. Several clinical studies have highlighted ROS1 as a promising therapeutic target because crizotinib, a multi-targeted drug against ROS1, ALK, and the MET proto-oncogene, has elicited remarkable responses in ROS1-rearrangements NSCLC. However, acquired resistance mediated by ROS1 kinase domain mutations has been identified and a system to assess ROS1 inhibitors for these resistant mutations is necessary for the promotion of drug development...
May 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29731604/a-network-pharmacology-approach-to-determine-the-synergetic-mechanisms-of-herb-couple-for-treating-rheumatic-arthritis
#6
Xi-Xi Xu, Jian-Ping Bi, Li Ping, Ping Li, Fei Li
Purpose: The purpose of this study was to investigate the therapeutic mechanism(s) of Clematis chinensis Osbeck/ Notopterygium incisum K.C. Ting ex H.T (CN). Methods: A network pharmacology approach integrating prediction of ingredients, target exploration, network construction, module partition and pathway analysis was used. Results: This approach successfully helped to identify 12 active ingredients of CN, interacting with 13 key targets (Akt1, STAT3, TNFsf13, TP53, EPHB2, IL-10, IL-6, TNF, MAPK8, IL-8, RELA, ROS1 and STAT4)...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29729495/braf-in-non-small-cell-lung-cancer-nsclc-pickaxing-another-brick-in-the-wall
#7
REVIEW
Alessandro Leonetti, Francesco Facchinetti, Giulio Rossi, Roberta Minari, Antonia Conti, Luc Friboulet, Marcello Tiseo, David Planchard
Molecular characterization of non-small cell lung cancer (NSCLC) marked an historical turning point for the treatment of lung tumors harboring kinase alterations suitable for specific targeted drugs inhibition, translating into major clinical improvements. Besides EGFR, ALK and ROS1, BRAF represents a novel therapeutic target for the treatment of advanced NSCLC. BRAF mutations, found in 1.5-3.5% of NSCLC, are responsible of the constitutive activation of mitogen activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway...
April 24, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29704675/efficacy-of-crizotinib-among-different-types-of-ros1-fusion-partners-in-patients-with-ros1-rearranged-non-small-cell-lung-cancer
#8
Ziming Li, Lan Shen, Ding Ding, Jia Huang, Jie Zhang, Zhiwei Chen, Shun Lu
INTRODUCTION: ROS1 rearrangement-positive non-small-cell lung cancer (NSCLC) can be treated effectively, with an anaplastic lymphoma kinase (ALK)/ROS1/mesenchymal-epithelial transition factor inhibitor such as crizotinib. However the rate of response remains variable. Although several ROS1 fusion partners have been identified, the efficacy of crizotinib in patients with different types of ROS1 fusion partners is poorly understood. METHODS: We reviewed clinicopathological data of patients with ROS1-rearrangement who received crizotinib therapy at our institution between April 2014 and December 2016...
April 25, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29697418/recent-progress-in-systemic-treatment-for-lung-cancer
#9
Jeffrey W Clark, Dan L Longo
PURPOSE OF REVIEW: We intend to highlight progress made in 2017 to lung cancer molecular nosology and application of new knowledge to treatment. RECENT FINDINGS: Studies have shown that agents targeting specific molecular defects in lung cancers such as epidermal growth factor receptor(egfr) mutations, alk or ros1 gene rearrangements, are more effective than conventional combination chemotherapy as primary treatment for various lung cancer subgroups. Identification of mechanisms of drug resistance has guided development of improved agents and effective salvage regimens...
April 24, 2018: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29690662/-expert-consensus-on-diagnosis-of-ros1-gene-fusion-positive-non-small-cell-lung-cancer
#10
(no author information available yet)
No abstract text is available yet for this article.
April 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29690661/-guidenline-for-diagnosis-and-treatment-of-alk-and-ros1-positive-non-small-cell-lung-cancer-in-china
#11
X C Zhang, S Lu, L Zhang, M L Liao, C L Wang, Y Cheng, G D Li, S J Mok, C Huang, X Q Liu, J Wang, M Z Wang, Y P Zhang, J Y Zhou, X J Zhou, X Y Zhou, D M Lin, J J Yang, Y Song, C P Hu, K Wang, Y He, H Li, W Z Zhong, Y L Wu
No abstract text is available yet for this article.
April 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29683453/a-blood-based-test-for-the-detection-of-ros1-and-ret-fusion-transcripts-from-circulating-ribonucleic-acid-using-digital-polymerase-chain-reaction
#12
Hestia S Mellert, Kristin E Alexander, Leisa P Jackson, Gary A Pestano
We have developed novel methods for the isolation and characterization of tumor-derived circulating ribonucleic acid (cRNA) for blood-based liquid biopsy. Robust detection of cRNA recovered from blood represents a solution to a critical unmet need in clinical diagnostics. The test begins with the collection of whole blood into blood collection tubes containing preservatives that stabilize cRNA. Cell-free, exosomal, and platelet-associated RNA is isolated from plasma in this test system. The cRNA is reverse transcribed to complementary DNA (cDNA) and amplified using digital polymerase chain reaction (dPCR)...
April 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29666465/molecular-epidemiology-of-lung-cancer-in-iran-implications-for-drug-development-and-cancer-prevention
#13
REVIEW
Zahra Fathi, Nicholas L Syn, Jian-Guo Zhou, Raheleh Roudi
Epidemiological studies undertaken over the past decades reveal a gradual but progressive increase in the incidence and mortality attributable to lung cancer in the Islamic Republic of Iran, a sovereign state geographically situated at the crossroads of Central Eurasia and Western Asia. We identified references published in English and Persian through searches of PubMed, EMBASE, Web of Science, Scopus, and the Scientific Information Database (SID)-a specialized Iranian database, which indexes Iranian scientific journals-between inception and 15 September 2017...
April 18, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29666135/study-protocol-for-the-saron-trial-a-multicentre-randomised-controlled-phase-iii-trial-comparing-the-addition-of-stereotactic-ablative-radiotherapy-and-radical-radiotherapy-with-standard-chemotherapy-alone-for-oligometastatic-non-small-cell-lung-cancer
#14
John Conibear, Brendan Chia, Yenting Ngai, Andrew Tom Bates, Nicholas Counsell, Rushil Patel, David Eaton, Corinne Faivre-Finn, John Fenwick, Martin Forster, Gerard G Hanna, Susan Harden, Philip Mayles, Syed Moinuddin, David Landau
INTRODUCTION: Following growing evidence to support the safety, local control (LC) and potential improvement in overall survival (OS) in patients with oligometastatic non-small cell lung cancer (NSCLC) that have been treated with local ablative therapy such as stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS), we initiate the SARON trial to investigate the impact and feasibility of adding SABR/SRS and radical radiotherapy (RRT) following standard chemotherapy on OS...
April 17, 2018: BMJ Open
https://www.readbyqxmd.com/read/29665843/next-generation-sequencing-analysis-of-receptor-type-tyrosine-kinase-genes-in-surgically-resected-colon-cancer-identification-of-gain-of-function-mutations-in-the-ret-proto-oncogene
#15
Duarte Mendes Oliveira, Katia Grillone, Chiara Mignogna, Valentina De Falco, Carmelo Laudanna, Flavia Biamonte, Rosa Locane, Francesco Corcione, Massimiliano Fabozzi, Rosario Sacco, Giuseppe Viglietto, Donatella Malanga, Antonia Rizzuto
BACKGROUND: Improvement in genetic characterization of Colon Cancer (CC) patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments. One of the most relevant cancer-specific actionable targets are receptor tyrosine kinases (RTKs) whose role in CC need to be better investigated. METHODS: We have analysed 37 CC patients using the Ion AmpliSeq™ Comprehensive Cancer Panel (CCP)...
April 17, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29652780/implication-of-biomarker-mutations-for-predicting-survival-in-patients-with-metastatic-lung-cancer-to-the-spine
#16
Bryan D Choi, Ganesh M Shankar, Ahilan Sivaganesan, Laura A Van Beaver, Kevin Oh, John H Shin
STUDY DESIGN: A retrospective cohort study. OBJECTIVE: We performed a retrospective study of patients treated at our institution over the last 7 years to ascertain whether gene expression signatures in patients with advanced metastatic disease are associated with survival, when the disease has progressed to the spine. SUMMARY OF BACKGROUND DATA: Spinal metastases are a major cause of morbidity in patients with cancer. Molecular profiling strategies to characterize lung cancer have identified several genetic biomarkers that may lead to more effective prognostication...
April 12, 2018: Spine
https://www.readbyqxmd.com/read/29626621/first-in-human-phase-i-study-of-ac0010-a-mutant-selective-egfr-inhibitor-in-non-small-cell-lung-cancer-safety-efficacy-and-potential-mechanism-of-resistance
#17
Yuxiang Ma, Xin Zheng, Hongyun Zhao, Wenfeng Fang, Yang Zhang, Jieying Ge, Lu Wang, Weicong Wang, Ji Jiang, Shaokun Chuai, Zhou Zhang, Wanhong Xu, Xiao Xu, Pei Hu, Li Zhang
INTRODUCTION: AC0010 is a mutation-selective, third-generation EGFR tyrosine kinase inhibitor (TKI). This first-in-human phase I trial determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AC0010 in patients with advanced or recurrent NSCLC and acquired resistance to the first-generation EGFR-TKI. METHODS: Patients received escalating daily doses of AC0010 (50 to 600 mg) throughout 28-day cycles...
April 4, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29623743/immunoexpression-of-bap1-ros1-and-alk-in-spitzoid-melanocytic-tumors
#18
Leonardo Cardili, Cristiano Ribeiro Viana, Andressa Germano, Mariana Fernandes, Denise Barcellos, Gilles Landman
BACKGROUND: Spitzoid tumors are a heterogeneous group of melanocytic neoplasms that frequently imposes diagnostic difficulties. Lately, several advances in molecular biology afforded significant discoveries on the pathogenesis of these tumors. BAP1 (BRCA-1 associated protein-1) inactivation and anomalous expression of kinase translocation-related proteins are among the main criteria launched by new classification proposals. Our aim was to systematically assess the immunoexpression of BAP1, ROS1 (receptor tyrosine kinase c-Ros oncogene 1), and ALK (anaplastic lymphoma receptor tyrosine kinase) proteins in an unpublished series of spitzoid tumors...
April 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29617048/pseudosarcomatous-myofibroblastic-proliferations-of-the-genitourinary-tract-are-genetically-different-from-nodular-fasciitis-and-lack-usp6-ros1-and-etv6-gene-rearrangements
#19
Judith As Jebastin, Steven C Smith, Kyle D Perry, Nilesh S Gupta, Shaheen Alanee, Shannon Carskadon, Dhananjay A Chitale, Nallasivam Palanisamy, Sean R Williamson
AIMS: Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract have a debatable relationship to inflammatory myofibroblastic tumour (generally lacking ALK rearrangement); however, they share several overlapping features with nodular fasciitis of soft tissue. Since rearrangement of the USP6 gene has been recently recognized as a recurrent alteration in soft tissue nodular fasciitis, and several other alternative gene fusions have been recently recognized in inflammatory myofibroblastic tumour, we studied whether USP6, ROS1, or ETV6 gene rearrangements were present in these lesions (12 cases)...
April 4, 2018: Histopathology
https://www.readbyqxmd.com/read/29610289/e-cadherin-ros1-inhibitor-synthetic-lethality-in-breast-cancer
#20
Ilirjana Bajrami, Rebecca Marlow, Marieke van de Ven, Rachel Brough, Helen N Pemberton, Jessica Frankum, Feifei Song, Rumana Rafiq, Asha Konde, Dragomir B Krastev, Malini Menon, James Campbell, Aditi Gulati, Rahul Kumar, Stephen J Pettitt, Mark D Gurden, Marta Llorca Cardenosa, Irene Chong, Patrycja Gazinska, Fredrik Wallberg, Elinor J Sawyer, Lesley-Ann Martin, Mitch Dowsett, Spiros Linardopoulos, Rachael Natrajan, Colm J Ryan, Patrick W B Derksen, Jos Jonkers, Andrew N J Tutt, Alan Ashworth, Christopher J Lord
The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells with CRISPR/Cas9-engineered CDH1 mutations, we identified synthetic lethality between E-cadherin deficiency and inhibition of the tyrosine kinase ROS1. Data from large-scale genetic screens in molecularly diverse breast tumor cell lines established that the E-cadherin/ROS1 synthetic lethality was not only robust in the face of considerable molecular heterogeneity but was also elicited with clinical ROS1 inhibitors, including foretinib and crizotinib...
April 2018: Cancer Discovery
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