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MERTK: upstream from BRAF

U.S. researchers have shown that inhibiting c-Mer proto-oncogene tyrosine kinase, a protein that sits upstream from BRAF, reduced melanoma growth in mice.1 Future studies will need to determine whether inhibitors of this kinase are effective in BRAF-resistant tumors.

c-Mer proto-oncogene tyrosine kinase (MERTK) is a member of the TAM receptor family of transmembrane proteins that includes TYRO3 protein tyrosine kinase (TYRO3; Sky) and AXL receptor tyrosine kinase (AXL; UFO). MERTK is expressed on at least three types of normal cells: platelets, for which it aids their aggregation; macrophages, which it enables to engulf target cells; and a range of epithelial cell types, for which it plays a role in survival.

Studies by multiple groups have shown that MERTK is overexpressed or hyperactivated-and thus a potential therapeutic target-in leukemia2 and in prostate,3 brain4 and lung5 cancers. At least one study has shown that TAM and other tyrosine kinase receptors are activated in melanoma,6 and two more have linked TYRO3, AXL and the TAM receptor ligand, growth arrest-specific 6 (GAS6), to melanoma tumorigenesis

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