Figures & data
Figure 1 Schematic diagram representing MEK inhibitor-sensitive reactivation of MAPK signaling following BRAF inhibitor resistance.
Notes: Mutations and dysregulation of factors within the MAPK pathway that contribute to BRAF inhibitor resistance include: increased activity of RTKs either through higher levels of ligand stimulation or an RTK mutation providing constitutive activity; loss of NF1 inhibitory function; single point-mutations or increased levels of RAS; copy-number gain, or alternative splicing of BRAF, or increased CRAF; activation of MEK kinase independent of RAF by MLKs; and loss of ERK-dependent negative feedback. Dashed lines represent loss of effective inhibition. Faded NF1 represents complete loss of expression.
Abbreviations: NF1, neurofibromin-1; RTK, receptor tyrosine kinase; MLK, mixed lineage kinases; ERK, extracellular-signal-regulated kinase; MAPK, mitogen-activated protein kinase.
Abbreviations: NF1, neurofibromin-1; RTK, receptor tyrosine kinase; MLK, mixed lineage kinases; ERK, extracellular-signal-regulated kinase; MAPK, mitogen-activated protein kinase.
Table 1 Summary of the clinical trials and outcome measures for combination vemurafenib and cobimetinib therapy
Figure 2 Schematic diagram representing aberrant signaling pathways responsible for resistance to BRAF or MEK inhibitors in metastatic melanoma and pharmacological strategies to overcome this resistance.
Notes: Briefly, the molecular mechanisms of resistance to BRAF or MEK inhibitors in metastatic melanoma are highlighted. Pharmacological agents targeting key factors of these pathways undergoing clinical trials are listed.
Abbreviations: PDGFR, platelet-derived growth factor receptor; IGF, insulin-like growth factor; ERK, extracellular-signal-regulated kinase.
Abbreviations: PDGFR, platelet-derived growth factor receptor; IGF, insulin-like growth factor; ERK, extracellular-signal-regulated kinase.
