Abstract
Raf are conserved, ubiquitous serine/protein kinases discovered as the cellular elements hijacked by transforming retroviruses. The three mammalian RAF proteins (A, B and CRAF) can be activated by the human oncogene RAS, downstream from which they exert both kinase-dependent and kinase-independent, tumor-promoting functions. The kinase-dependent functions are mediated chiefly by the MEK/ERK pathway, whose activation is associated with proliferation in a broad range of human tumors. Almost 10 years ago, activating BRAF mutations were discovered in a subset of human tumors, and in the past year treatment with small-molecule RAF inhibitors has yielded unprecedented response rates in melanoma patients. Thus, Raf qualifies as an excellent molecular target for anticancer therapy. This review focuses on the role of BRAF and CRAF in different aspects of carcinogenesis, on the success of molecular therapies targeting Raf and the challenges they present.
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Acknowledgements
We thank all the members of the Baccarini lab for helpful discussions and apologize to all the colleagues whose work could not be cited in this review for reasons of space. The Baccarini lab is supported by the Austrian Scientific Research Fund (Grants P19530 and SFB 021) and the European Community (Grants INFLA-CARE and GROWTHSTOP).
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Maurer, G., Tarkowski, B. & Baccarini, M. Raf kinases in cancer–roles and therapeutic opportunities. Oncogene 30, 3477–3488 (2011). https://doi.org/10.1038/onc.2011.160
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DOI: https://doi.org/10.1038/onc.2011.160
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