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Ras-Raf-MAPK
SHCGrb2
SOS1
PP
P
Raf1Raf1P
MEK2P
MEK1P
Grb2, growth factor receptor-bound protein 2
RasRas
ERK2ERK2
ERK1ERK1
SHCGrb2
SOS1
PP
P
Raf1Raf1P
MEK2P
ERK2ERK2P
P
ERK1ERK1 PP
MEK1P
Transcription factorsTranscription factorsGrb2, growth factor receptor-bound protein 2; SRF, serum response factor
RasRas
SRF SRFTranscriptionTranscription
Ras-Raf-MAPK
Attivazione costitutiva di Ras-Raf-MAPK
Raf1Raf1P
MEK2P
ERK2ERK2P
P
ERK1ERK1 PP
MEK1P
SRF SRF
RasRas
TranscriptionTranscription
Ras
Zarnestra (Tipifarnib, R115777) Sarasar (Lonafarnib, SCH66336)
EVIDENCE FOR ARas-INDEPENDENT EFFECT FOR FTIs
•Lack of correlation between susceptibility and Ras status
•Differences in the kinetics of development of the effects • Inhibition of K-Ras- and N-Ras-dependent cell growth
REOVIRUS (Respiratory Enteric Orphan Virus)
Attivazione costitutiva di Ras-Raf-MAPK
Raf1Raf1P
MEK2P
ERK2ERK2P
P
ERK1ERK1 PP
MEK1P
SRF SRF
RasRas
TranscriptionTranscription
Ras
SORAFENIB (Nexavar®): Low molecular weight inhibitor of VEGFR,
PDGFR, KIT, RET and Raf-1 kinase activity
Mechanism of action of sorafenib