Roles of c-Met and RON kinases in tumor progression and their potential as therapeutic targets

Katherine Chang, Anand Karnad, Shujie Zhao and James W. Freeman _

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Oncotarget. 2015; 6:3507-3518. https://doi.org/10.18632/oncotarget.3420

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Katherine Chang1,2, Anand Karnad1,2, Shujie Zhao1 and James W. Freeman1,2,3

1 Department of Medicine, Division of Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

2 Cancer Therapy and Research Center, Experimental and Developmental Therapeutics Program, San Antonio, TX, USA

3 Research and Development, Audie Murphy Veterans Administration Hospital, San Antonio, TX, USA

Correspondence to:

James W. Freeman, email:

Keywords: c-Met, RON kinase, Met inhibitors

Received: December 18, 2014 Accepted: January 21, 2015 Published: January 31, 2015


c-Met and receptor originated from nantes (RON) are structurally related transmembrane phosphotyrosine kinase receptors. c-Met and RON show increased expression or activity in a variety of tumors leading to tumor progression and may play a role in acquired resistance to therapy. Although often co-expressed, the distinct functional roles of c-Met and RON are not fully understood. c-Met and RON form both activated homodimers and heterodimers with themselves and other families of phosphotyrosine kinase receptors. Inhibitors for c-Met and RON including small molecular weigh kinase inhibitors and neutralizing antibodies are in pre-clinical investigation and clinical trials. Several of the tyrosine kinase inhibitors have activity against both c-Met and RON kinases whereas the antibodies generally are target specific. As with many targeted agents used to treat solid tumors, it is likely that c-Met/RON inhibitors will have greater benefit when used in combination with chemotherapy or other targeted agents. A careful analysis of c-Met/RON expression or activity and a better elucidation of how they influence cell signaling will be useful in predicting which tumors respond best to these inhibitors as well as determining which agents can be used with these inhibitors for combined therapy.

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