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https://www.readbyqxmd.com/read/28434509/lonely-driver-ros1
#1
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
#2
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
#3
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...
April 13, 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
#4
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
https://www.readbyqxmd.com/read/28428274/egfr-mediates-responses-to-small-molecule-drugs-targeting-oncogenic-fusion-kinases
#5
Aria Vaishnavi, Laura Schubert, Uwe Rix, Lindsay A Marek, Anh T Le, Stephen Keysar, Magdalena J Glogowska, Matthew A Smith, Severine L Kako, Natalia J Sumi, Kurtis D Davies, Kathryn E Ware, Marileila Varella-Garcia, Eric B Haura, Antonio Jimeno, Lynn E Heasley, Dara L Aisner, Robert C Doebele
Oncogenic kinase fusions of ALK, ROS1, RET and NTRK1 act as drivers in human lung and other cancers. Residual tumor burden following treatment of ALK or ROS1+ lung cancer patients with oncogene-targeted therapy ultimately enables the emergence of drug-resistant clones, limiting the long-term effectiveness of these therapies. To determine the signaling mechanisms underlying incomplete tumor cell killing in oncogene-addicted cancer cells, we investigated the role of EGFR signaling in drug-naive cancer cells harboring these oncogene fusions...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427247/molecular-testing-of-lung-cancers
#6
Hyo Sup Shim, Yoon-La Choi, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Mee Sook Roh, Tae-Jung Kim, Seung Yeon Ha, Jin-Haeng Chung, Se Jin Jang, Geon Kook Lee
Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics...
April 21, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28415793/clinical-framework-for-next-generation-sequencing-based-analysis-of-treatment-predictive-mutations-and-multiplexed-gene-fusion-detection-in-non-small-cell-lung-cancer
#7
Kajsa Ericson Lindquist, Anna Karlsson, Per Levéen, Hans Brunnström, Christel Reuterswärd, Karolina Holm, Mats Jönsson, Karin Annersten, Frida Rosengren, Karin Jirström, Jaroslaw Kosieradzki, Lars Ek, Åke Borg, Maria Planck, Göran Jönsson, Johan Staaf
Precision medicine requires accurate multi-gene clinical diagnostics. We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot mutation concordance), after which 533 consecutive NSCLCs were collected during one-year of routine clinical analysis in the healthcare region (~90% advanced stage patients)...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400043/association-of-the-genetic-markers-for-myocardial-infarction-with-sudden-cardiac-death
#8
Anastasiya A Ivanova, Vladimir N Maksimov, Pavel S Orlov, Dinara E Ivanoshchuk, Sergei V Savchenko, Mikhail I Voevoda
OBJECTIVE: Investigate the association of rs17465637 gene MIAF3 (1q41), rs1376251 gene TAS2R50 (12p13), rs4804611 gene ZNF627 (19p13), rs619203 gene ROS1 (6q22), rs1333049 (9p21), rs10757278 (9p21), rs2549513 (16q23), rs499818 (6p24) associated with myocardial infarction available from the international genome-wide studies with sudden cardiac death (SCD) in a case-control study. METHODS: A sample of SCD cases (n=285) was formed using the WHO criteria; the control sample (n=421) was selected according to sex and age...
April 2017: Indian Heart Journal
https://www.readbyqxmd.com/read/28387643/novel-gopc-fig-ros1-fusion-in-a-pediatric-high-grade-glioma-survivor
#9
Erin N Kiehna, Maxine R Arnush, Benita Tamrazi, Jennifer A Cotter, Debra Hawes, Nathan J Robison, Cindy Y Fong, Dolores B Estrine, Jennifer H Han, Jaclyn A Biegel
Pediatric high-grade glioma is a rare tumor characterized by high mortality. The authors report the first case of a high-grade glioma associated with a GOPC(FIG)-ROS1 fusion in a pediatric patient. The patient underwent gross-total resection at the age of 4 years, followed by adjuvant high-dose chemotherapy and autologous hematopoietic stem cell rescue. At 30 months after transplantation, she remains disease free.
April 7, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28378229/advances-in-the-development-of-molecularly-targeted-agents-in-non-small-cell-lung-cancer
#10
Saoirse O Dolly, Dearbhaile C Collins, Raghav Sundar, Sanjay Popat, Timothy A Yap
Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that involves personalized strategies based on histological and molecular subtypes. The molecular era has revolutionized the treatment of patients harboring epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 gene aberrations. In the appropriately selected population, anti-tumor agents against these molecular targets can significantly improve progression-free survival...
April 4, 2017: Drugs
https://www.readbyqxmd.com/read/28361443/gaining-insight-into-crizotinib-resistance-mechanisms-caused-by-l2026m-and-g2032r-mutations-in-ros1-via-molecular-dynamics-simulations-and-free-energy-calculations
#11
XiaoYun Wu, Yu Fu, YuanYuan Wang, ShanHe Wan, JiaJie Zhang
ROS1 fusion kinase-highly expressed in a variety of human cancers-has emerged as an important and attractive target for anticancer drug design. Crizotinib, a well-known drug approved by the FDA as an ALK inhibitor to treat advanced NSCLC, also shows potent inhibitoy activity against ROS1. However, the development of serious resistance due to secondary mutations has been observed in clinical studies. To provide insight into the mechanisms of this drug resistance, molecular dynamics simulations and free-energy calculations were carried out for complexes of crizotinib with wild-type (WT) ROS1 as well as the mutated L2026M and G2032R forms...
April 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28346673/clinical-features-of-bim-deletion-polymorphism-and-its-relation-with-crizotinib-primary-resistance-in-chinese-patients-with-alk-ros1-fusion-positive-non-small-cell-lung-cancer
#12
Limin Zhang, Tao Jiang, Xuefei Li, Yan Wang, Chao Zhao, Sha Zhao, Lei Xi, Shijia Zhang, Xiaozhen Liu, Yijun Jia, Hui Yang, Jinpeng Shi, Chunxia Su, Shengxiang Ren, Caicun Zhou
BACKGROUND: The authors' previous study demonstrated that the B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (BCL2L11) (Bim) deletion polymorphism was associated with poor clinical response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC) with EGFR mutations. The objective of the current study was to investigate the impact of the Bim deletion polymorphism among patients with anaplastic lymphoma kinase (ALK)-positive or ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)-positive NSCLC who were treated with crizotinib...
March 27, 2017: Cancer
https://www.readbyqxmd.com/read/28342334/oncogene-addiction-in-non-small-cell-lung-cancer-focus-on-ros1-inhibition
#13
REVIEW
Francesco Facchinetti, Giulio Rossi, Emilio Bria, Jean-Charles Soria, Benjamin Besse, Roberta Minari, Luc Friboulet, Marcello Tiseo
Detection of molecular aberrations driving the biology and the clinical behavior of advanced non-small cell lung cancer (NSCLC) allows the adoption of specific therapeutic strategies dramatically impacting disease courses. Among these, ROS1 rearrangements are present in 1-2% of lung adenocarcinomas. Thanks to similarities between ALK and ROS1 oncogenes, lessons inferred from ALK can be applied to ROS1-positive NSCLC; nevertheless, disparities exist between diseases mastered by these two fusion genes. In the absence of more common genetic alterations detected in NSCLC (e...
March 12, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28336956/preclinical-development-of-a-humanized-neutralizing-antibody-targeting-hgf
#14
Hyori Kim, Sung Hee Hong, Jung Yong Kim, In-Chull Kim, Young-Whan Park, Song-Jae Lee, Seong-Won Song, Jung Ju Kim, Gunwoo Park, Tae Min Kim, Yun-Hee Kim, Jong Bae Park, Junho Chung, In-Hoo Kim
Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336808/potent-dual-bet-bromodomain-kinase-inhibitors-as-value-added-multi-targeted-chemical-probes-and-cancer-therapeutics
#15
Stuart W Ember, Que T Lambert, Norbert Berndt, Steven Gunawan, Muhammad Ayaz, Marilena Tauro, Jin-Yi Zhu, Paula J Cranfill, Patricia Greninger, Conor C Lynch, Cyril H Benes, Harshani R Lawrence, Gary W Reuther, Nicholas J Lawrence, Ernst Schonbrunn
Synergistic action of kinase and BET bromodomain inhibitors in cell killing has been reported for a variety of cancers. Using the chemical scaffold of the JAK2 inhibitor TG101348 we developed and characterized single agents which potently and simultaneously inhibit BRD4 and a specific set of oncogenic tyrosine kinases including JAK2, FLT3, RET, and ROS1. Lead compounds showed on-target inhibition in several blood cancer cell lines and were highly efficacious at inhibiting the growth of hematopoietic progenitor cells from myeloproliferative neoplasm (MPN) patients...
March 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28335727/overexpression-of-snapdragon-delila-del-gene-in-tobacco-enhances-anthocyanin-accumulation-and-abiotic-stress-tolerance
#16
Aung Htay Naing, Kyeung Il Park, Trinh Ngoc Ai, Mi Young Chung, Jeung Sul Han, Young-Wha Kang, Ki Byung Lim, Chang Kil Kim
BACKGROUND: Rosea1 (Ros1) and Delila (Del) co-expression controls anthocyanin accumulation in snapdragon flowers, while their overexpression in tomato strongly induces anthocyanin accumulation. However, little data exist on how Del expression alone influences anthocyanin accumulation. RESULTS: In tobacco (Nicotiana tabacum 'Xanthi'), Del expression enhanced leaf and flower anthocyanin production through regulating NtCHS, NtCHI, NtF3H, NtDFR, and NtANS transcript levels...
March 23, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28332047/mechanisms-of-resistance-to-target-therapies-in-non-small-cell-lung-cancer
#17
Francesco Facchinetti, Claudia Proto, Roberta Minari, Marina Garassino, Marcello Tiseo
Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28318251/molecular-simulation-studies-on-the-binding-selectivity-of-type-i-inhibitors-in-the-complexes-with-ros1-versus-alk
#18
Yuanxin Tian, Yonghuan Yu, Yudong Shen, Hua Wan, Shan Chang, Tingting Zhang, Shanhe Wan, Jiajie Zhang
ROS1 and ALK are promising targets of anticancer drugs for non-small-cell lung cancer. Since they have 49% amide acid sequence homology in the kinases domain and 77% identity at the ATP binding area, some ALK inhibitors also showed some significant responses for ROS1 in the clinical trial, such as the type-I binding inhibitor crizotinib and PF-06463922. As a newly therapeutic target, the selective ROS1 inhibitor is relatively rare. Moreover, the molecular basis for the selectivity of ROS1 versus ALK still remains unclear...
April 24, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28280984/treatment-of-lung-adenocarcinoma-by-molecular-targeted-therapy-and-immunotherapy
#19
REVIEW
Motonobu Saito, Hiroyuki Suzuki, Koji Kono, Seiichi Takenoshita, Takashi Kohno
Lung adenocarcinoma (LADC) is a cancer treatable using targeted therapies against driver gene aberrations. EGFR mutations and ALK fusions are frequent gene aberrations in LADC, and personalized therapies against those aberrations have become a standard therapy. These targeted therapies have shown significant positive efficacy and tolerable toxicity compared to conventional chemotherapy, so it is necessary to identify additional druggable genetic aberrations. Other than EGFR mutations and ALK fusions, mutations in KRAS, HER2, and BRAF, and driver fusions involving RET and ROS1, have also been identified in LADC...
March 9, 2017: Surgery Today
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#20
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
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