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Comment
. 2015 Sep 14;28(3):279-81.
doi: 10.1016/j.ccell.2015.08.006.

Path Forward for RAF Therapies: Inhibition of Monomers and Dimers

Robert L Kortum  1 , Deborah K Morrison  2
Affiliations
Comment

Path Forward for RAF Therapies: Inhibition of Monomers and Dimers

Robert L Kortum et al. Cancer Cell. .

Abstract

Current BRAF inhibitors block signaling from monomeric BRAF(V600E), but not from oncogenic RAS, which requires RAF dimerization. In this issue of Cancer Cell, Yao and colleagues investigate why current drugs are ineffective against RAF dimers, while Peng and colleagues describe a pan-RAF inhibitor targeting both monomeric and dimeric RAF.

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Figures

Figure 1.
Figure 1.
Next Generation RAF Inhibitors. (Left panel) Oncogenic BRAF mutants evade normal ERK-mediate feedback inhibition and gain RAS-independence by functioning as either activated monomers or constitutive homodimers. Current BRAF drugs block signaling from activated monomers but not dimeric RAF, due to negative cooperativity in protomer binding. (Right panel) Next generation pan-RAF inhibitors target RAF monomers and dimers.
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References

    1. Bucheit AD, and Davies MA (2014). Emerging insights into resistance to BRAF inhibitors in melanoma. Biochem Pharmacol 87, 381–389. - PubMed
    1. Fedorenko IV, Paraiso KH, and Smalley KS (2011). Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma. Biochem Pharmacol 82, 201–209. - PMC - PubMed
    1. Freeman AK, Ritt DA, and Morrison DK (2013). Effects of Raf dimerization and its inhibition on normal and disease-associated Raf signaling. Mol Cell 49, 751–758. - PMC - PubMed
    1. Gibney GT, Messina JL, Fedorenko IV, Sondak VK, and Smalley KS (2013). Paradoxical oncogenesis--the long-term effects of BRAF inhibition in melanoma. Nat Rev Clin Oncol 10, 390–399. - PMC - PubMed
    1. Girotti MR, Lopes F, Preece N, Niculescu-Duvaz D, Zambon A, Davies L, Whittaker S, Saturno G, Viros A, Pedersen M, et al. (2015). Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma. Cancer Cell 27, 85–96. - PMC - PubMed

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