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. 2019 Mar 25;19:266. doi: 10.1186/s12885-019-5489-4

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© The Author(s). 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Fig. 4 — Dual inhibition of B-Raf and C-Raf inhibits melanoma tumour progression. a B-Raf inhibition leads to the Ras negative feedback mechanism switching to C-Raf driven tumourigenesis via potentiation of the Raf/MEK/ERK signalling axis. b PPL-008 (PDE8A – C-Raf disrupter peptide) binds to C-Raf, preventing PDE8A localisation within the C-Raf cAMP microdomain and exposing serine 259 – C-Raf to inhibitory phosphorylation by PKA. Co-treatment with B-Raf inhibitor and PPL-008 blocks onco-Ras driven tumour progression via inhibition of the Raf/MEK/ERK axis