AXL receptor tyrosine kinase signalling drives metastasis and disease progression in a number of human cancers, representing a promising oncology target. However, attempts to therapeutically target the AXL receptor have been limited by modest antitumour efficacy and substantial off-target effects. Now, Kariolis et al. have engineered an AXL decoy receptor, MYD1 Fc, which binds the AXL ligand GAS6 with high affinity, efficiently reducing GAS6-mediated AXL phosphorylation and downstream signalling. In mouse models of advanced ovarian and breast cancer, MYD1 Fc potently inhibited metastasis and disease progression, an effect which correlated with GAS6 affinity.
References
Kariolis, M. S. et al. An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis. Nat. Chem. Biol. http://dx.doi.org/10.1038/nchembio.1636 (2014)
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Crunkhorn, S. Decoy receptor prevents metastasis. Nat Rev Drug Discov 13, 812 (2014). https://doi.org/10.1038/nrd4463
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DOI: https://doi.org/10.1038/nrd4463
