Inhibiting Eph kinase activity may not be "Eph"ective for cancer treatment
Abstract Several Eph receptor tyrosine kinases (RTKs) are commonly over-expressed in epithelial and mesenchymal cancers and are recognized as promising therapeutic targets. Although normal interaction between Eph receptors and their ephrin ligands stimulates kinase activity and is generally tumor su...
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Published in | Growth factors (Chur, Switzerland) Vol. 32; no. 6; pp. 207 - 213 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
Informa UK Ltd
01.12.2014
Taylor & Francis |
Subjects | |
Online Access | Get full text |
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Summary: | Abstract
Several Eph receptor tyrosine kinases (RTKs) are commonly over-expressed in epithelial and mesenchymal cancers and are recognized as promising therapeutic targets. Although normal interaction between Eph receptors and their ephrin ligands stimulates kinase activity and is generally tumor suppressive, significant Eph over-expression allows activation of ligand- and/or kinase-independent signaling pathways that promote oncogenesis. Single-agent kinase inhibitors are widely used to target RTK-driven tumors but acquired and de novo resistance to such agents is a major limitation to effective clinical use. Accumulating evidence suggests that Ephs can be inhibited by "leaky" or low-specificity kinase inhibitors targeted at other RTKs. Such off-target effects may therefore inadvertently promote ligand- and/or kinase-independent oncogenic Eph signaling, thereby providing a new mechanism by which resistance to the RTK inhibitors can emerge. We propose that combining specific, non-leaky kinase inhibitors with tumor-suppressive stimulators of Eph signaling may provide more effective treatment options for overcoming treatment-induced resistance and clinical failure. |
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ISSN: | 0897-7194 1029-2292 |
DOI: | 10.3109/08977194.2014.985293 |