scholarly journals RNA-Based Multiplexing Assay for Routine Testing of Fusion and Splicing Variants in Cytological Samples of NSCLC Patients

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 15
Author(s):  
Cristina Aguado ◽  
Ana Giménez-Capitán ◽  
Ruth Román ◽  
Sonia Rodríguez ◽  
Núria Jordana-Ariza ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Housekeeping Genes ◽  
Complete Response ◽  
Routine Testing ◽  
Splicing Variants ◽  
Geometrical Mean ◽  
Nsclc Patients ◽  
Selection Of

The detection of ALK receptor tyrosine kinase (ALK), ROS proto-oncogen1, receptor tyrosine kinase (ROS1), ret proto-oncogen (RET), and MET proto-oncogen exon 14 skipping (METΔex14) allows for the selection of specific kinase inhibitor treatment in patients with non-small cell lung cancer (NSCLC). Multiplex technologies are recommended in this setting. We used nCounter, a multiplexed technology based on RNA hybridization, to detect ALK, ROS1, RET, and METΔex14 in RNA purified from cytological specimens (n = 16) and biopsies (n = 132). Twelve of the 16 cytological samples (75.0%) were evaluable by nCounter compared to 120 out of 132 (90.9%) biopsies. The geometrical mean (geomean) of the housekeeping genes of the nCounter panel, but not the total amount of RNA purified, was significantly higher in biopsies vs. cytological samples. Among cytological samples, we detected ALK (n = 3), METΔex14 (n = 1) and very high MET expression (n = 1) positive cases. The patient with METΔex14 had a partial response to tepotinib, one of the patients with ALK fusions was treated with crizotinib with a complete response. Cell blocks and cytological extensions can be successfully used for the detection of fusions and splicing variants using RNA-based methods such as nCounter.

scholarly journals Glomerular Changes in Rats Administered ABT-869, a Multitargeted Receptor Tyrosine Kinase Inhibitor - Linking Ultrastructure to Mechanism

2009 ◽  
Vol 15 (S2) ◽  
pp. 16-17
Author(s):  
J Fagerland ◽  
S Morgan
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Receptor Tyrosine Kinase Inhibitor

Extended abstract of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009

scholarly journals Új célzott terápiás lehetőség az onkológiában: tropomiozin receptor-tirozin-kináz gátlók

2021 ◽  
Vol 162 (34) ◽  
pp. 1362-1369
Author(s):  
Edina Kiss ◽  
Zsuzsanna Pápai
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
First Generation ◽  
Kinase Inhibitor ◽  
Disease Free Survival ◽  
Diagnostic Methods ◽  
Molecular Diagnostic ◽  
Precision Oncology ◽  
Gene Fusions ◽  
Trk Inhibitors

Összefoglaló. A molekuláris diagnosztikai módszerek folyamatos fejlődésének köszönhetően egyre több onkogén genetikai eltérést azonosítanak. A neurotrofikus tropomiozin receptor-tirozin-kináz (NTRK-) génfúziók fontos precíziós onkológiai célpontok, melyek mindhárom NTRK-génben előfordulhatnak, onkogén-hajtóerőként viselkednek. A génfúziók különböző molekuláris diagnosztikai módszerekkel azonosíthatók, melyek közül a legpontosabb, legköltségesebb és legidőigényesebb meghatározást az újgenerációs szekvenálási technika jelenti. A tropomiozin receptor-tirozin-kináz (TRK-) fúziós fehérjék szelektív gátlása személyre szabott onkológiai kezelési lehetőséget jelent a tumor típusától, lokalizációjától és a beteg életkorától függetlenül. Az első generációs TRK-gátlók gyors, hatékony és tartós daganatellenes hatást biztosítanak kimutatott NTRK-fúzió-pozitív daganatok esetén, alacsony mellékhatásprofil mellett. Az első generációs TRK-gátlók mellett jelentkező ’on target’ rezisztenciát a második generációs TRK-gátlók oldják fel. Szekvenciális tirozin-kináz-inhibitor-kezeléssel tartós betegségmentes túlélés érhető el. Orv Hetil. 2021; 162(34): 1362–1369. Summary. Due to the continuous development of molecular diagnostic methods, more and more oncogenic genetic abnormalities are being identified. Neurotrophic tropomyosin receptor tyrosine kinase (NTRK) gene fusions are important precision oncology targets that can occur in all three NTRK genes and act as oncogenic drivers. Gene fusions can be identified by a variety of molecular diagnostic technologies, of which next-generation sequencing is the most accurate, costly and time-consuming determination. Selective inhibition of tropomyosin receptor tyrosine kinase (TRK) fusion proteins represents a personalized oncology treatment option regardless of tumour type, localization and patient age. First-generation TRK inhibitors provide rapid, efffective and long-lasting antitumor activity in NTRK fusion-positive tumors with a low side-effect profile. On target resistance to first-generation TRK inhibitors is resolved by second-generation TRK inhibitors. Durable disease-free survival can be achieved with sequential tyrosine kinase inhibitor therapies. Orv Hetil. 2021; 162(34): 1362–1369.

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