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|Ref Type||Journal Article|
|Authors||Yeh I, Tee MK, Botton T, Shain AH, Sparatta AJ, Gagnon A, Vemula SS, Garrido MC, Nakamaru K, Isoyama T, McCalmont TH, LeBoit PE, Bastian BC|
|Title||NTRK3 kinase fusions in Spitz tumours.|
|Journal||The Journal of pathology|
|Abstract Text||Oncogenic fusions in TRK family receptor tyrosine kinases have been identified in several cancers and can serve as therapeutic targets. We identified ETV6-NTRK3, MYO5A-NTRK3 and MYH9-NTRK3 fusions in Spitz tumours, and demonstrated that NTRK3 fusions constitutively activate the mitogen-activated protein kinase, phosphoinositide 3-kinase and phospholipase Cγ1 pathways in melanocytes. This signalling was inhibited by DS-6051a, a small-molecule inhibitor of NTRK1/2/3 and ROS1. NTRK3 fusions expand the range of oncogenic kinase fusions in melanocytic neoplasms and offer targets for a small subset of melanomas for which no targeted options currently exist. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|DS-6051a||ROS1 Inhibitor 14 Trk Receptor Inhibitor (Pan) 23||DS-6051a is the free base form of DS-6051b that inhibits ROS1 and NTRK1/2/3, which may lead to growth inhibition in tumor cells (PMID: 27477320).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|ETV6 - NTRK3||melanoma||sensitive||DS-6051a||Preclinical - Cell culture||Actionable||In a preclinical study, DS-6051a inhibited MAPK, PI3K, and PLCgamma-1 signaling in transformed melanocytes expressing ETV6-NTRK3 in culture (PMID: 27477320).||27477320|