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. Author manuscript; available in PMC: 2014 Apr 28.
Published in final edited form as: Biochem Pharmacol. 2011 May 25;82(3):201–209. doi: 10.1016/j.bcp.2011.05.015

Figure 3. Mechanisms of acquired resistance to BRAF inhibitors.

Figure 3

Multiple mechanisms of acquired BRAF inhibitor resistance have been identified. BRAF V600E melanoma cells chronically treated with BRAF inhibitors acquire drug resistance via switching between the three isoforms of RAF (ARAF, BRAF, CRAF) to activate the MAPK pathway. Increased IGFR1 and PDGFR signaling may also allow for resistance by activating PI3K/AKT signaling as well as other pathways. Resistance can also arise following the reactivation of the MAPK pathway, this can occur following the acquisition of activating mutations in NRAS (Q61K) and MEK (C121S) and the increased expression of the MAP3K8 (COT).