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https://www.readbyqxmd.com/read/28538401/atrial-fibrillation-was-changed-into-sinus-bradycardia-in-a-ros1-positive-advanced-lung-adenocarcinoma-patient-who-achieved-durable-response-to-crizotinib-a-case-report-and-literature-review
#1
Lan Liu, Jing Wu, Wei Zhao, Mei-Juan Huang
RATIONAL: The c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearrangements represent a new and rare genetic subtype of non-small-cell lung cancer. In recent years, the use of crizotinib in ROS1-rearranged lung cancer exhibits significant clinical efficacy. Crizotinib is generally well tolerated and the most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac, and endocrine abnormalities. From a cardiac perspective, crizotinib is associated with 2 main cardiac effects, QT interval prolongation and bradycardia...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28529902/current-state-of-immunotherapy-for-non-small-cell-lung-cancer
#2
REVIEW
Jyoti Malhotra, Salma K Jabbour, Joseph Aisner
Lung cancer is the leading cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Platinum-based doublet chemotherapy is the standard first-line treatment for metastatic NSCLC when genomic testing reveals no targetable alteration such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation/re-arrangements. But, chemotherapy produces response rates ranging only between 15-30%. For patients whose disease progresses on first-line chemotherapy, second-line therapy historically consists of taxane-based salvage chemotherapy with a response rate of less than 25%...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28520528/expanding-the-roster-of-ros1-inhibitors
#3
Ibiayi Dagogo-Jack, Alice T Shaw
No abstract text is available yet for this article.
May 18, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28520527/open-label-multicenter-phase-ii-study-of-ceritinib-in-patients-with-non-small-cell-lung-cancer-harboring-ros1-rearrangement
#4
Sun Min Lim, Hye Ryun Kim, Jong-Seok Lee, Ki Hyeong Lee, Yun-Gyoo Lee, Young Joo Min, Eun Kyung Cho, Sung Sook Lee, Bong-Seog Kim, Moon Young Choi, Hyo Sup Shim, Jin-Haeng Chung, Yoon La Choi, Min Jeong Lee, Maria Kim, Joo-Hang Kim, Siraj M Ali, Myung-Ju Ahn, Byoung Chul Cho
Purpose ROS1 rearrangement is a distinct molecular subset of non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of ceritinib in patients with ROS1-rearranged NSCLC. Patients and Methods We enrolled 32 patients with advanced NSCLC who tested positive for ROS1 rearrangement by fluorescent in situ hybridization. Ceritinib 750 mg was administered once daily. The primary end point was objective response rate. The secondary end points were disease control rate; duration of response; progression-free survival; overall survival; toxicity; and concordance among fluorescent in situ hybridization, immunohistochemistry, and next-generation sequencing...
May 18, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28515245/biomarker-based-treatment-selection-in-non-small-cell-lung-cancer
#5
Wallace Akerley
Patients with non-small cell lung cancer must be tested for biomarkers. Currently, treatments directed against EGFR, ALK, and ROS1 mutations are standard of care. A number of emerging new targets and treatments are on the horizon.
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28515244/what-when-and-how-of-biomarker-testing-in-non-small-cell-lung-cancer
#6
Gregory L Riely
Biomarker testing is recommended for all patients diagnosed with non-small cell lung cancer. At a minimum, testing should include the mutations/fusions EGFR, ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA-approved therapies are available for these alterations. Other actionable molecular findings include RET rearrangements, BRAF(V600E) mutations, and MET exon 14 alterations. If adequate testing was not performed at treatment initiation, molecular testing should be performed before administration of subsequent lines of therapy...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28507144/critical-roles-of-dna-demethylation-in-the-activation-of-ripening-induced-genes-and-inhibition-of-ripening-repressed-genes-in-tomato-fruit
#7
Zhaobo Lang, Yihai Wang, Kai Tang, Dengguo Tang, Tatsiana Datsenka, Jingfei Cheng, Yijing Zhang, Avtar K Handa, Jian-Kang Zhu
DNA methylation is a conserved epigenetic mark important for genome integrity, development, and environmental responses in plants and mammals. Active DNA demethylation in plants is initiated by a family of 5-mC DNA glycosylases/lyases (i.e., DNA demethylases). Recent reports suggested a role of active DNA demethylation in fruit ripening in tomato. In this study, we generated loss-of-function mutant alleles of a tomato gene, SlDML2, which is a close homolog of the Arabidopsis DNA demethylase gene ROS1 In the fruits of the tomato mutants, increased DNA methylation was found in thousands of genes...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28502721/met-exon-14-skipping-mutations-in-lung-adenocarcinoma-clinicopathologic-implications-and-prognostic-values
#8
Geun Dong Lee, Seung Eun Lee, Doo-Yi Oh, Dan-Bi Yu, Hae Min Jeong, Jooseok Kim, Sungyoul Hong, Hun Soon Jung, Ensel Oh, Ji-Young Song, Mi-Sook Lee, Mingi Kim, Kyungsoo Jung, Jhingook Kim, Young Kee Shin, Yoon-La Choi, Hyeong Ryul Kim
INTRODUCTION: Response to MET inhibitors in non-small cell lung cancer with MET exon 14 (METex14) skipping has fueled molecular screening efforts and search for optimal therapies. However, further work is needed to refine the clinicopathologic and prognostic implications of METex14 skipping METHODS: Among 795 East-Asian patients who underwent surgery for non-small cell lung cancer, we screened 45 patients with quintuple-negative (EGFR-/KRAS-/ALK-/ROS1-/RET-) lung adenocarcinomas using RT-PCR, and found 17 patients (37...
May 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28490045/uterine-inflammatory-myofibroblastic-tumors-frequently-harbor-alk-fusions-with-igfbp5-and-thbs1
#9
Josh D Haimes, Colin J R Stewart, Brian A Kudlow, Brady P Culver, Bo Meng, Eleanor Koay, Ann Whitehouse, Nichola Cope, Jen-Chieh Lee, Tony Ng, W Glenn McCluggage, Cheng-Han Lee
Inflammatory myofibroblastic tumor (IMT) can occur in a number of anatomic sites, including the uterus. Like its soft tissue counterpart, uterine IMT frequently expresses ALK and harbors ALK genetic rearrangements. The aim of this study is to fully characterize the genetic fusions that occur in uterine IMT. We studied 11 uterine IMTs with typical histology and 8 uterine myxoid smooth muscle tumors (5 leiomyomas, 1 smooth muscle tumor of uncertain malignant potential, and 2 leiomyosarcomas) in which the differential of IMT was considered, using a RNA-sequencing-based fusion assay to detect genetic fusions involving ALK, ROS1, RET, NTRK1/3, and other genes...
June 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28469773/crizotinib-synergizes-with-cisplatin-in-preclinical-models-of-ovarian-cancer
#10
Xiao-Xiu Huang, Feng-Feng Xie, Li-Jiao Hou, Xiu-Xiu Chen, Rong-Ying Ou, Jiang-Tao Yu, Jian-Ge Qiu, Wen-Ji Zhang, Qi-Wei Jiang, Yang Yang, Di-Wei Zheng, Yao Chen, Jia-Rong Huang, Kun Wang, Meng-Ning Wei, Wen-Feng Li, Zhi Shi, Xiao-Jian Yan
Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene. However, the anticancer effect of crizotinib on ovarian cancer is still unclear. In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28468034/-to-evaluate-the-clinicopathologic-characteristics-and-outcome-of-tumor-cells-spreading-through-air-spaces-in-patients-with-adenocarcinoma-of-lung
#11
P L Sun, J N Liu, L Q Cao, M Yao, H W Gao
Objective: To investigate the clinicopathologic features, molecular characteristics and prognosis of spread through air space (STAS) in patients with adenocarcinoma of the lung. Methods: Two hundred and eighty-eight lung adenocarcinoma patients with complete clinicopathologic and follow-up data were included. The patients were divided into STAS positive (178 cases) and negative (110 cases) groups.EGFR and KRAS gene mutations were detected by amplification refractory mutation system (ARMS), and ALK and ROS1 gene fusion were detected by fluorescence in situ hybridization method...
May 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28468033/-clinicopathologic-features-and-genetic-profile-of-the-redefined-large-cell-lung-carcinoma
#12
L K Hou, L P Zhang, W Zhang, Y Huang, W Wu, Z W Dong, C Y Wu
Objective: To investigate the clinicopathologic features and genetic profile of large cell lung carcinoma (LCC) redefined by new classification. Methods: Basing on 2015 WHO classification criteria in redefining large cell lung carcinoma, the expression of specific markers (TTF1, Napsin A, p40, CK5/6, CK, vimentin and ZEB1) was detected by immunohistochemistry and D-PAS staining in 303 surgically-removed lung specimens previously diagnosed as large cell lung carcinoma. The clinicopathologic and genetic characteristics (including EGFR, KRAS, BRAF, ALK and ROS1 gene mutation) were analyzed...
May 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28465216/ros1-protein-tyrosine-kinase-inhibitors-in-the-treatment-of-ros1-fusion-protein-driven-non-small-cell-lung-cancers
#13
REVIEW
Robert Roskoski
ROS1 protein-tyrosine kinase fusion proteins are expressed in 1-2% of non-small cell lung cancers. The ROS1 fusion partners include CD74, CCDC6, EZR, FIG, KDELR2, LRIG3, MSN, SDC4, SLC34A2, TMEM106B, TMP3, and TPD52L1. Physiological ROS1 is closely related to the ALK, LTK, and insulin receptor protein-tyrosine kinases. ROS1 is a so-called orphan receptor because the identity of its activating ligand, if any, is unknown. The receptor is expressed during development, but little is expressed in adults and its physiological function is unknown...
April 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28460468/pd-l1-expression-and-its-relationship-with-oncogenic-drivers-in-non-small-cell-lung-cancer-nsclc
#14
Liyan Jiang, Xinying Su, Tianwei Zhang, Xiaolu Yin, Meizhuo Zhang, Haihua Fu, Hulin Han, Yun Sun, Lili Dong, Jialin Qian, Yanhua Xu, Xuan Fu, Paul R Gavine, Yanbin Zhou, Kun Tian, Jiaqi Huang, Dong Shen, Haiyi Jiang, Yihong Yao, Baohui Han, Yi Gu
In order to explore the potential patient population who could benefit from anti PD-1/PD-L1 mono or combination therapies, this study aimed to profile a panel of immunotherapy related biomarkers (PD-1, PD-L1, CTLA-4 and CD8) and targeted therapy biomarkers (EGFR, KRAS, ALK, ROS1 and MET) in NSCLC.Tumor samples from 297 NSCLC patients, including 156 adenocarcinomas (AD) and 129 squamous cell carcinomas (SCC), were analyzed using immunohistochemistry, immunofluorescence, sequencing and fluorescence in situ hybridization...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28449809/genomic-diagnostics-leading-to-the-identification-of-a-tfg-ros1-fusion-in-a-child-with-possible-atypical-meningioma
#15
Maria Rossing, Christina Westmose Yde, Astrid Sehested, Olga Østrup, David Scheie, Volodia Dangouloff-Ros, Birgit Geoerger, Gilles Vassal, Karsten Nysom
Meningiomas are rare in children. They are highly complex, harboring unique clinical and pathological characteristics, and many occur in patients with neurofibromatosis type 2. Hereby, we present a case of a two-year-old boy presented with a diagnostically challenging intraventricular tumor. It was incompletely resected 6 times over 14 months but kept progressing and was ultimately deemed unresectable. Histologically, the tumor was initially classified as schwannoma, but extensive international review concluded it was most likely an atypical meningioma, WHO grade II...
April 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28448556/a-highly-specific-and-sensitive-massive-parallel-sequencer-based-test-for-somatic-mutations-in-non-small-cell-lung-cancer
#16
Yoshiaki Inoue, Jun Shiihara, Hitoshi Miyazawa, Hiromitsu Ohta, Megumi Higo, Yoshiaki Nagai, Kunihiko Kobayashi, Yasuo Saijo, Masanori Tsuchida, Mitsuo Nakayama, Koichi Hagiwara
Molecular targeting therapy for non-small cell lung cancer (NSCLC) has clarified the importance of mutation testing when selecting treatment regimens. As a result, multiple-gene mutation tests are urgently needed. We developed a next-generation sequencer (NGS)-based, multi-gene test named the MINtS for investigating driver mutations in both cytological specimens and snap-frozen tissue samples. The MINtS was used to investigate the EGFR, KRAS, BRAF genes from DNA, and the ERBB2, and the ALK, ROS1, and RET fusion genes from RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28434509/lonely-driver-ros1
#17
EDITORIAL
Spasenija Savic, Sacha Rothschild, Lukas Bubendorf
No abstract text is available yet for this article.
May 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28433076/identification-of-ntrk3-fusions-in-childhood-melanocytic-neoplasms
#18
Lu Wang, Klaus J Busam, Ryma Benayed, Robert Cimera, Jiajing Wang, Ryan Denley, Mamta Rao, Ruth Aryeequaye, Kerry Mullaney, Long Cao, Marc Ladanyi, Meera Hameed
Spitzoid neoplasms are a distinct group of melanocytic tumors. Genetically, they lack mutations in common melanoma-associated oncogenes. Recent studies have shown that spitzoid tumors may contain a variety of kinase fusions, including ROS1, NTRK1, ALK, BRAF, and RET fusions. We report herein the discovery of recurrent NTRK3 gene rearrangements in childhood melanocytic neoplasms with spitzoid and/or atypical features, based on genome-wide copy number analysis by single-nucleotide polymorphism array, which showed intragenic copy number changes in NTRK3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28431340/first-macrocyclic-3-rd-generation-alk-inhibitor-for-treatment-of-alk-ros1-cancer-clinical-and-designing-strategy-update-of-lorlatinib
#19
REVIEW
Sulman Basit, Zaman Ashraf, Kwangho Lee, Muhammad Latif
Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to 2(nd)-generation ALK inhibitors. Lorlatinib (PF-06463922) (6) is a 3(rd)-generation macrocyclic ALK-TKI that demonstrates many advantages over 2(nd)-generation ALK inhibitors. Lorlatinib has demonstrated decent kinase selectivity, promising pharmacokinetic profile, selective brain-penetration and strong antiproliferative activity in several ALK/ROS1-driven tumor models. The current review describes the activity spectrum, key events from discovery to clinical applications and the evidences that lorlatinib acts as an ALK/ROS1 inhibitor in clinical settings...
July 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28428782/a-recombinant-potato-virus-y-infectious-clone-tagged-with-the-rosea1-visual-marker-pvy-ros1-facilitates-the-analysis-of-viral-infectivity-and-allows-the-production-of-large-amounts-of-anthocyanins-in-plants
#20
Teresa Cordero, Mohamed A Mohamed, Juan-José López-Moya, José-Antonio Daròs
Potato virus Y (PVY) is a major threat to the cultivation of potato and other solanaceous plants. By inserting a cDNA coding for the Antirrhinum majus Rosea1 transcription factor into a PVY infectious clone, we created a biotechnological tool (PVY-Ros1) that allows infection by this relevant plant virus to be tracked by the naked eye with no need for complex instrumentation. Rosea1 is an MYB-type transcription factor whose expression activates the biosynthesis of anthocyanin pigments in a dose-specific and cell-autonomous manner...
2017: Frontiers in Microbiology
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