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Novel activating NTRK2 and NTRK3 mutations as biomarkers for NTRK inhibitor sensitivity in cancer


OHSU # 2339

Technology Overview:

Neurotrophic receptor tyrosine kinases (NTRK) are a family of genes involved in neuronal development. Mutations in these proteins result in dysregulation of neurons and may increase the risk of disease. NTRK gene fusions have previously been implicated as oncogenic drivers in various solid tumors.


Researchers at OHSU have now identified four novel activating missense point mutations in the NTRK 2 and 3 genes, which confer oncogenic potential in certain leukemias.  All four transforming NTRK mutations are sensitive at low nanomolar concentrations to several NTRK inhibitors, including entrectinib (RXDX-101), cabozantinib (XL-184), and foretinib (XL-880).  Thus, these mutations can serve as novel biomarkers of response to NTRK targeted inhibitors in leukemias, as well as other cancers. 



Qian K, Tognon CE,  Wagner J, Davare M, Druker BJ. Characterization of transforming NTRK2 and NTRK3 mutations identified in leukemia patient samples. Blood, 2016 128: 1566


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Anne Carlson
Technology Development Manager