2009_-_nexavar.pptx
Nexavar™ Sorafenib
A Multikinase inhibitor
January 2009
Chloé DINGREVILLE Diane-Laurène SMAL Aurélie TELLIER
2
2 major isoforms:
B-Raf
C-Raf or Raf1
EGFR
VEGFR
Ras
Raf
MEK
ERK
Voie MAPK
VEGF
Ser/Thr
Kinase
PDGFR
PDGF
Initial target: Raf
EGF
Raf:
Often hyper activated in human solid tumour:
1. caused by activation oncogenic mutations:
as b-raf V600E mutation
•Prevalent in melanomas 63%
•Papillary thyroid carcinoma 50%
2. Activation upstream of oncogenic ras mutants (K-
ras )
•90% of pancreatic cancers
•30% of Hepatocellular carcinoma HCC
•35% of Non-Squamous-cell lung cancers
NSCLC
•15% of melanoma
•10% of kidney RCC
3. expression of upstream growth factor or/ and their
RTKs
•renal cell carcinoma (RCC) 50%
•hepatocellular carcinoma (HCC) 100%
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100%
