Raf kinases: Oncogenesis and drug discovery

Raf kinase signaling has been thoroughly investigated over the last 20 years. A-Raf, B-Raf and C-Raf, the 3 mammalian members of the Raf family, are involved in a variety of cellular processes such as growth, proliferation, survival, differentiation and transformation. The detection of B-RAF mutations in a wide, variety of human cancers, the description of wildtype and mutant B-RAF as tumor antigens in melanoma and the promising outcome of clinical trials evaluating the Raf inhibitor Nexavar (R) (Sorafenib, BAY 43-9006) have sparked a broad interest in the scientific community. After a short historical detour and an introduction into Raf kinase signaling, we are going to discuss here recent outcomes of Raf kinase research with respect to tumor formation and give an overview on current efforts to develop anticancer therapies interfering with aberrant Raf kinase signaling. (c) 2006 Wiley-Liss, Inc.