This week in therapeutics

Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Cancer

Lung cancer

Neurotrophic tyrosine kinase receptor 1 (NTRK1; TrkA)

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.
Array BioPharma Inc. has ARRY-470 in preclinical testing for cancer.
Nerviano Medical Sciences s.r.l. has PHA-848125, an inhibitor of cyclin dependent kinases (CDKs) and TrkA, in Phase II testing to treat cancer.
Amgen Inc. and Tesaro Inc. have the dual TrkA and anaplastic lymphoma kinase (ALK) inhibitor TSR-011 in Phase I/II testing to treat non-small cell lung cancer (NSCLC).

SciBX 6(45); doi:10.1038/scibx.2013.1287
Published online Nov. 21, 2013

Patent application filed; licensing status undisclosed

Vaishnavi, A. et al. Nat. Med.; published online Oct. 27, 2013;
doi:10.1038/nm.3352
Contact: Robert C. Doebele, University of Colorado Denver School of Medicine, Aurora, Co.
e-mail:
robert.doebele@ucdenver.edu
Contact: Pasi A. Jänne, Dana-Farber Cancer Institute, Boston, Mass.
e-mail:
pasi_janne@dfci.harvard.edu