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https://www.readbyqxmd.com/read/29136733/-exploratory-study-of-circulating-tumor-dna-detection-in-early-breast-cancer-an-analysis-of-75-next-generation-sequencing-results
#1
B Zhou, L Xin, L Xu, Y H Liu, M M Zhang, R L Jing, X Y Liang, S B Cao
Objective: To explore the utility of circulating tumor DNA detection in early breast cancer by using next-generation sequencing. Methods: This exploratory study of circulating tumor DNA detection is for early invasive breast cancer patients treated in Breast Disease Center, Peking University First Hospital from December 2015 to July 2016. Plasma samples were collected and were used to isolate plasma cell-free DNA.Exons or hotspots of 247 cancer related genes were sequenced by next-generation sequencing. Mutations and their correlation with clinic-pathological factors were analyzed...
November 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29134959/targeting-ret-driven-cancers-lessons-from-evolving-preclinical-and-clinical-landscapes
#2
REVIEW
Alexander Drilon, Zishuo I Hu, Gillianne G Y Lai, Daniel S W Tan
The gene encoding the receptor-tyrosine kinase RET was first discovered more than three decades ago, and activating RET rearrangements and mutations have since been identified as actionable drivers of oncogenesis. Several multikinase inhibitors with activity against RET have been explored in the clinic, and confirmed responses to targeted therapy with these agents have been observed in patients with RET-rearranged lung cancers or RET-mutant thyroid cancers. Nevertheless, response rates to RET-directed therapy are modest compared with those achieved using targeted therapies matched to other oncogenic drivers of solid tumours, such as sensitizing EGFR or BRAF(V600E) mutations, or ALK or ROS1 rearrangements...
November 14, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29130105/tumor-molecular-profiling-of-nsclc-patients-using-next-generation-sequencing
#3
Nikolaos Tsoulos, Eirini Papadopoulou, Vasiliki Metaxa-Mariatou, Georgios Tsaousis, Chrisoula Efstathiadou, Georgia Tounta, Aikaterini Scapeti, Eugenia Bourkoula, Pavlos Zarogoulidis, George Pentheroudakis, Stylianos Kakolyris, Ioannis Boukovinas, Pavlos Papakotoulas, Elias Athanasiadis, Theofanis Floros, Anna Koumarianou, Vasileios Barbounis, Anca Dinischiotu, George Nasioulas
Non‑small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissues...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29128428/clinical-and-translational-implications-of-ret-rearrangements-in-non-small-cell-lung-cancer
#4
REVIEW
Roberto Ferrara, Nathalie Auger, Edouard Auclin, Benjamin Besse
Since the discovery in 2012 of RET rearrangements in non-small cell lung cancer (NSCLC), at least 12 different fusion variants have been identified, with KIF5B-RET being the most frequent and the best characterized. Unlike ALK and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry, although fluorescence in situ hybridization and reverse transcriptase PCR are fully complementary diagnostic tools. In large retrospective studies, RET rearrangements correlate with adenocarcinoma histology, never-smoking status, younger age, more advanced stage disease, potentially higher chemo-sensitivity (in particular to pemetrexed-based regimens), and coexistence of other genomic alterations...
November 8, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29125548/liquid-biopsy-and-therapeutic-targets-present-and-future-issues-in-thoracic-oncology
#5
REVIEW
Paul Hofman
The practice of liquid biopsy (LB) has revolutionized the care of patients with metastatic lung cancer. Many oncologists now use this approach in daily practice, applying precise procedures for the detection of activating or resistance mutations in EGFR. These tests are performed with plasma DNA and have been approved as companion diagnostic test for patients treated with tyrosine kinase inhibitors. ALK is another important target in lung cancer since it leads to treatment of patients who are positive for a rearrangement in ALK identified with tumor tissue...
November 10, 2017: Cancers
https://www.readbyqxmd.com/read/29114473/immunohistochemistry-for-predictive-biomarkers-in-non-small-cell-lung-cancer
#6
REVIEW
Mari Mino-Kenudson
In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC...
October 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29114472/molecular-diagnostics-of-lung-cancer-in-the-clinic
#7
REVIEW
Lynette Sholl
According to current practice guidelines, all patients with advanced non-small cell lung cancer (NSCLC) should undergo predictive biomarker testing. For squamous cell carcinoma patients, PD-L1 immunohistochemistry is indicated to select patients for immunotherapy in the first line. For lung adenocarcinoma, all patients with advanced disease should undergo testing for epidermal growth factor receptor (EGFR) mutations, ALK and ROS1 rearrangements, and PD-L1 expression to predict response to EGFR, ALK, or ROS1 targeted inhibitors or immunotherapy, respectively...
October 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29114471/beyond-alk-and-ros1-ret-ntrk-egfr-and-braf-gene-rearrangements-in-non-small-cell-lung-cancer
#8
REVIEW
Anna F Farago, Christopher G Azzoli
The discovery of gene rearrangements involving the receptor tyrosine kinase genes ALK and ROS1 has revolutionized management of the subset of non-small cell lung cancers characterized by these alterations. The oncogenic fusion proteins expressed in these tumors drive cancer cell growth and survival, and targeted inhibition of this signaling can lead to dramatic and durable responses in patients. While the best characterized gene fusions in non-small cell lung cancer (NSCLC) involve ALK and ROS1, fusions involving other kinases including RET, NTRK, EGFR and BRAF are now established as additional targetable drivers...
October 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29101161/lorlatinib-is-well-tolerated-and-has-activity-in-alk-and-ros1-nsclc
#9
(no author information available yet)
Lorlatinib achieved systemic and intracranial responses in patients with ALK- and ROS1-positive NSCLC.
November 3, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29101158/lorlatinib-in-alk-nsclc-robust-phase-ii-efficacy-seen
#10
(no author information available yet)
The investigational ALK inhibitor lorlatinib, whose early clinical activity was first reported last year, continues to look promising in advanced ALK-positive or ROS1-positive non-small cell lung cancer. In a phase II study, robust responses were seen in previously untreated patients, as well as those who had received as many as three prior ALK inhibitors.
November 3, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29078211/-personalized-therapy-of-lung-cancer-current-standard-and-future-challenges
#11
Richard Riedel, Jürgen Wolf
So called "personalized therapy" has revolutionized the care of non-small cell lung cancer (NSCLC). The discovery of more and more driver mutations in NSCLC has led to a molecular defined sub classification of lung cancer patients. For four driver mutations (EGFR(mut), ALK(transl), ROS1(transl), BRAF-V600(mut)) firstline approved drugs are available and became the treatment of choice. Further drugs are in clinical development or can be used as off-label treatment. The emergence of resistance under targeted therapy, the development of new drugs for further driver mutations and the broad implementation of molecular diagnostics for all lung cancer patients are future challenges...
November 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29078035/dual-control-of-ros1-mediated-active-dna-demethylation-by-the-dna-damage-binding-protein-2-ddb2
#12
Dolores Córdoba-Cañero, Valérie Cognat, Rafael R Ariza, Teresa Roldán Arjona, Jean Molinier
DNA methylation contributes to key regulatory processes during plant development by controlling gene expression. Genomic methylation patterns are dynamic and must be properly maintained and/or re-established upon DNA replication and active removal, therefore requiring sophisticated control mechanisms. Here, we identified a direct interplay between the DNA repair factor DNA DAMAGE BINDING protein 2 (DDB2) and the ROS1-mediated active DNA demethylation pathway in Arabidopsis thaliana. We showed that DDB2 forms a complex with ROS1 and AGO4 and that they act at ROS1 locus to modulate DNA methylation levels and therefore ROS1 expression...
October 27, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29076659/cytological-findings-of-ros1-rearranged-lung-adenocarcinoma
#13
Naoto Kuroda, Hiroyuki Tamiya, Kimiko Nakatani, Haruna Ide, Yukari Wada, Kaori Yasuoka, Masahiko Ohara, Keiko Mizuno, Kenji Yorita, Kengo Takeuchi
ROS1-rearranged lung adenocarcinoma has been recently identified. We report a case of ROS1-rearranged lung adenocarcinoma with special emphasis on cytological findings. Here, we report a case of young woman with ROS1-rearranged lung adenocarcinoma diagnosed by cytology and discuss the clinical, cytological, and molecular findings. Cytologically, the tumor consisted of small tight clusters of cells with high nuclear/cytoplasmic ratio. Nuclei were enlarged and small nucleoli were occasionally observed. Signet-ring cells were focally identified...
October 27, 2017: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/29074100/alk-and-ros1-rearrangement-in-nsclc-rapidly-evolving-standards
#14
Christine M Bestvina, Everett E Vokes
No abstract text is available yet for this article.
October 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29074098/lorlatinib-in-non-small-cell-lung-cancer-with-alk-or-ros1-rearrangement-an-international-multicentre-open-label-single-arm-first-in-man-phase-1-trial
#15
Alice T Shaw, Enriqueta Felip, Todd M Bauer, Benjamin Besse, Alejandro Navarro, Sophie Postel-Vinay, Justin F Gainor, Melissa Johnson, Jorg Dietrich, Leonard P James, Jill S Clancy, Joseph Chen, Jean-François Martini, Antonello Abbattista, Benjamin J Solomon
BACKGROUND: Most patients with anaplastic lymphoma kinase (ALK)-rearranged or ROS proto-oncogene 1 (ROS1)-rearranged non-small-cell lung cancer (NSCLC) are sensitive to tyrosine kinase inhibitor (TKI) therapy, but resistance invariably develops, commonly within the CNS. This study aimed to analyse the safety, efficacy, and pharmacokinetic properties of lorlatinib, a novel, highly potent, selective, and brain-penetrant ALK and ROS1 TKI with preclinical activity against most known resistance mutations, in patients with advanced ALK-positive or ROS1-positive NSCLC...
October 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29068003/understanding-and-targeting-resistance-mechanisms-in-nsclc
#16
REVIEW
Julia Rotow, Trever G Bivona
The expanding spectrum of both established and candidate oncogenic driver mutations identified in non-small-cell lung cancer (NSCLC), coupled with the increasing number of clinically available signal transduction pathway inhibitors targeting these driver mutations, offers a tremendous opportunity to enhance patient outcomes. Despite these molecular advances, advanced-stage NSCLC remains largely incurable due to therapeutic resistance. In this Review, we discuss alterations in the targeted oncogene ('on-target' resistance) and in other downstream and parallel pathways ('off-target' resistance) leading to resistance to targeted therapies in NSCLC, and we provide an overview of the current understanding of the bidirectional interactions with the tumour microenvironment that promote therapeutic resistance...
October 25, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29067878/brain-penetration-of-the-ros1-alk-inhibitor-lorlatinib-confirmed-by-pet
#17
T Lee Collier, Kevin P Maresca, Marc D Normandin, Paul Richardson, Timothy J McCarthy, Steven H Liang, Rikki N Waterhouse, Neil Vasdev
The Massachusetts General Hospital Radiochemistry Program, in collaboration with Pfizer, has developed unique (11)C and (18)F-labeling strategies to synthesize isotopologs of lorlatinib (PF-06463922) which is undergoing phase III clinical trial investigations for treatment of non-small-cell lung cancers with specific molecular alterations. A major goal in cancer therapeutics is to measure the concentrations of this drug in the brain metastases of patients with lung cancer, and penetration of the blood-brain barrier is important for optimal therapeutic outcomes...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/29066915/molecular-alterations-and-clinical-prognostic-factors-for-cholangiocarcinoma-in-thai-population
#18
N Trachu, E Sirachainan, N Larbcharoensub, W Rattanadech, S Detarkom, N Monnamo, K Kamprerasart, D MunTham, C Sukasem, T Reungwetwattana
This study explores genomic alterations in cholangiocarcinoma (CCC) tissues in Thai patients. We identified and reviewed the records of patients who had been diagnosed with CCC and for whom sufficient tumor samples for DNA and RNA extraction were available in our database. The specimens were explored for EGFR, KRAS, BRAF, and PIK3CA mutations and ROS1 translocation in 81 samples. Immunohistochemistry staining for HER2, ALK, and Ki-67 expression was tested in 74 samples. Prevalence of EGFR, KRAS, and PIK3CA mutations in this study was 21%, 12%, and 16%, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29066671/-landscape-of-lung-cancer-with-oligometastasis
#19
Yasushi Goto, Jun Sato
Lung cancer with a few to several metastases is so-called oligometastatic disease. Patient with recurrence only to limited site is also known as oligo-recurrence, and may be included as oligometastatic disease. From biological aspect, any existence of metastases is a sign of systemic disease. Due to the reports of long survival with only local treatment and without systemic disease in oligometastatic lung cancer, word of oligometastasis is used with fascinating expectation of cure to advanced lung cancer. Most of the previous reports are retrospective and no comprehensive data exists for selecting patient for local treatment to oligometastasis...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29061079/precision-oncology-neither-a-silver-bullet-nor-a-dream
#20
Nora S Sánchez, Gordon B Mills, Kenna R Mills Shaw
Precision oncology is not an illusion, nor is it the magic bullet that will eradicate all cancers. Precision oncology is simply another weapon in our growing armament against cancer. Rather than honing in on the failures of a relatively young field, one should advocate for integrating its successes into widespread clinical practice, especially for indications, such as: ABL, ALK, BRAF, BRCA1, BRCA2, EGFR, KIT, KRAS, PDGFRA, PDGFRB, ROS1, BCR-ABL, FLT3 and ROS1, where aberrations have been shown to alter responses to US FDA approved drugs - that is, level 1 data...
October 24, 2017: Pharmacogenomics
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