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c-Ros proto-oncogene 1
receptor tyrosine kinase

Mouse and cell culture studies suggest foretinib could help treat cancers harboring oncogenic ROS1 fusions and point mutations. In multiple cancer cell lines and in a mouse cholangiocarcinoma model expressing an oncogenic Ros1 variant, foretinib suppressed tumor cell proliferation more efficiently than the anaplastic lymphoma kinase (ALK) inhibitor Xalkori crizotinib, which also is known to inhibit ROS1. Cancer cells expressing ROS1-mutant proteins resistant to Xalkori were sensitive to foretinib. Next steps include evaluating foretinib in a clinical trial in patients with lung cancer carrying ROS1 fusions, including patients with crizotinib-resistant tumors. The trial is being designed by GlaxoSmithKline plc in partnership with the Oregon Health & Science University.
GSK's foretinib (GSK1363089) is in Phase I/II testing to treat breast, liver, non-small cell lung and renal cancer.
Pfizer Inc. markets Xalkori to treat non-small cell lung cancers (NSCLCs) carrying ALK fusions.

SciBX 6(48); doi:10.1038/scibx.2013.1378
Published online Dec. 19, 2013

Patent filed by OHSU; licensing details available from OHSU

Davare, M.A. et al. Proc. Natl. Acad. Sci. USA; published online Nov. 11, 2013;
Contact: Brian J. Druker, Oregon Health &
Science University, Portland, Ore.