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Raf kinases, the excellent molecular targets for anticancer therapy

     Raf kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes. Raf kinases mainly contain three mammalian RAF proteins (A, B and CRAF) and participate in the RAS-RAF-MEK-ERK signal pathways. Of which, B-Raf is the family member most easily activated by Ras, and the kinase activity of B-Raf is higher than that of C-Raf and, likely, A-Raf. Thus, the frequent mutational activation of BRAF is often observed in human tumors, but not CRAF or ARAF.


     Some studies indicated that overexpression of RAF or the truncated catalytic domain can lead to the activation of the ERK pathway in cultured cells and in vivo. On one hand, Raf can pomote cell proliferation through stimulation of the MEK/ERK pathway; on the other hand, downstream from activated Raf and Ras, the ERK pathway restrains apoptosis by regulating the expression and/or the activity of BCL-2 family members. Thus, RAF might potentially promote tumorigenesis using the two mechanisms[1].
     Accordingly, it is demonstrated that Raf kinases are critical targets for  molecule-target therapies of cancer. Recently, Raf inhibitors have been used in preclinical and clinical trials. For example, PLX4032, a drug specifically targeting BRAFV600E has recently produced a significant effect with response rates of 70–80% as single agent in metastatic melanoma patients[2].
     In conclusion, Raf is qualified as an excellent molecular target for anticancer therapy, Raf is still a attractive subject for basic and clinical researchers in the future.
References
[1]. Oncogene 2011; 30, 3477–3488.
[2]. N Engl J Med 2011; 363: 809–819.

Related Products

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S1267 Vemurafenib (PLX4032) Vemurafenib (PLX4032, RG7204, RO5185426) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM in cell-free assay. 10-fold selective for B-RafV600E over wild-type B-Raf in enzymatic assays and the cellular selectivity can exceed 100-fold. Vemurafenib (PLX4032, RG7204) induces autophagy.

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