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