Thursday, November 21, 2013
This week in therapeutics
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Neurotrophic tyrosine kinase receptor 1 (NTRK1;
In vitro and mouse studies suggest TrkA inhibitors could
help treat a subgroup of patients with lung cancer. In tumor samples from 91
patients with lung cancer, 3 patients carried NTRK1 gene fusions. In
noncancerous cells, expression of the gene fusions caused constitutive
activation of TrkA, the protein encoded by NTRK1, and induced
proliferation, anchorage-independent growth and tumor development when
implanted in mice. In fusion-expressing cells, TrkA inhibitors including ARRY-470
blocked TrkA autophosphorylation and cell proliferation. Next steps include a
clinical trial using Trk inhibitors in biomarker-selected patients.
BioPharma Inc. has ARRY-470 in preclinical testing for
Medical Sciences s.r.l. has PHA-848125,
an inhibitor of cyclin
dependent kinases (CDKs)
and TrkA, in Phase II testing to treat cancer.
Inc. and Tesaro
Inc. have the dual TrkA and anaplastic
lymphoma kinase (ALK)
in Phase I/II testing to treat non-small cell lung cancer (NSCLC).
Published online Nov. 21, 2013
Patent application filed;
licensing status undisclosed
Vaishnavi, A. et al.
Nat. Med.; published online Oct. 27, 2013;
Contact: Robert C. Doebele, University of Colorado Denver
School of Medicine, Aurora, Co.
Contact: Pasi A. Jänne, Dana-Farber Cancer Institute, Boston,
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