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Review
. 2013 Apr 25:6:30.
doi: 10.1186/1756-8722-6-30.

B-Raf and the inhibitors: from bench to bedside

Tiangui Huang  1 , Michael Karsy, Jian Zhuge, Minghao Zhong, Delong Liu
Affiliations
Review

B-Raf and the inhibitors: from bench to bedside

Tiangui Huang et al. J Hematol Oncol. .

Abstract

The B-Raf protein is a key signaling molecule in the mitogen activated protein kinase (MAPK) signaling pathway and has been implicated in the pathogenesis of a variety of cancers. An important V600E mutation has been identified and can cause constitutive B-Raf activation. Recent studies have evaluated a variety of small molecule inhibitors targeting B-Raf, including PLX4032/vemurafenib, dabrafenib, LGX818, GDC0879, XL281, ARQ736, PLX3603 (RO5212054), and RAF265. Therapeutic resistance has been identified and various mechanisms described. This review also discussed the current understanding of B-Raf signaling mechanism, methods of mutation detection, treatment strategies as well as potential methods of overcoming therapeutic resistance.

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Figures

Figure 1
Figure 1
B-Raf protein and signaling pathways. The B-Raf protein and its related signaling pathway are shown along with potential targets for treatment. A) The PI3K/AKT/mTOR and Ras/Raf/MAPK signaling pathways are shown along with potential targets. B) The structural domains of the B-Raf isoforms are shown. The position of the V600E mutation is indicated (arrow).
Figure 2
Figure 2
B-raf inhibitors in clinical development.
See this image and copyright information in PMC

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