Reference Detail

Ref Type Journal Article
PMID (23131561)
Authors Chi HT, Ly BT, Kano Y, Tojo A, Watanabe T, Sato Y
Title ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412.
Journal Biochemical and biophysical research communications
Vol 429
Issue 1-2
Date 2012 Dec 7
Abstract Text The ETV6-NTRK3 (EN) fusion gene which encodes a chimeric tyrosine kinase was first identified by cloning of the t(12;15)(p13;q25) translocation in congenital fibrosarcoma (CFS). Since then, EN has been also found in congenital mesoblastic nephroma (CMN), secretory breast carcinoma (SBC) and acute myelogenous leukemia (AML). Using IMS-M2 and M0-91 cell lines harboring the EN fusion gene, and Ba/F3 cells stably transfected with EN, we demonstrated that PKC412, also known as midostaurin, is an inhibitor of EN. Inhibition of EN activity by PKC412 suppressed the activity of it downstream molecules leading to inhibition of cell proliferation and induction of apoptosis. Our data for the first time suggested that PKC412 could serve as therapeutic drug for treatment of patients with this fusion.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
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 cancer sensitive Midostaurin Preclinical Actionable In a preclinical study, the broad spectrum kinase inhibitor midostaurin inhibited growth of cells dependent on the fusion protein ETV6-NTRK3, reducing ETV6-NTRK3 kinase activity and downstream signaling and inducing apoptosis (PMID: 23131561). 23131561