EGFR Signal Transduction in Tumor Cells R R R Gene iranseription and cell cycle progression evelin D1 Jun Fos
myc cyclin D1 Jun Fos R R R R EGFR Signal Transduction in Tumor Cells K K K K Gene transcription and cell cycle progression Gene transcription and cell cycle progression
EGFR Signal Transduction in Tumor Cells R R RAS RAF PI3-K Sos GRB2 MEK AKT MAPK Gene iran. cion and cell cy以 yression ao evelin D1 Jun Fos tion ls
Angiogenesis Metastasis myc cyclin D1 Jun Fos R R EGFR Signal Transduction in Tumor Cells K K R K R K Gene transcription and cell cycle progression Gene transcription and cell cycle progression MAPK MEK RAS RAF SOS GRB2 Proliferation PI3-K AKT Inhibition of apoptosis P P P P P P
IRESSA® ICso (uM) Selective enzyme inhibition -EGFR (ErbB-1): 0.033 Other cellular kinases >3 EGFR autophosphorylation <1 inhibition in tumor cell lines Tumor cell growth inhibition -EGF stimulated 0.054 Basal 8.8
IRESSA® IC50 (µM) • Selective enzyme inhibition – EGFR (ErbB-1): 0.033 – Other cellular kinases > 3 • EGFR autophosphorylation < 1 inhibition in tumor cell lines • Tumor cell growth inhibition – EGF stimulated 0.054 – Basal 8.8
IRESSAR Inhibits Growth of A549 Xenograft Tumors (NSCLC) IRESSA 200 mg/kg,po days 10-72 IRESSA 200 mg/kg,po days 10-30 0.8 AVehicle 0.7 0.6 0.5 0.4 0.3 0 0.1 8。"◇。.0" 0 0 20 40 60 80 Day
0 20 40 60 80 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 Day Mean tumor volume, cm3 IRESSA ® Inhibits Growth of A549 Xenograft Tumors (NSCLC) IRESSA 200 mg/kg, po days 10 - 72 IRESSA 200 mg/kg, po days 10 - 30 Vehicle
Herceptin (trastuzumab) is a chimeric (95% human)monoclonal antibody directed Extracellular domain 1632 amind acids) against the extra- Ligand-binding site cellular domain of the HER-2/neu receptor Intracellular domain (580 amino acids) Cetuximab/Erbitux/C- Tyrosine kinase activity 225:Anti-EGFR
• Herceptin (trastuzumab) is a chimeric (95% human) monoclonal antibody directed against the extracellular domain of the HER-2/neu receptor • Cetuximab/Erbitux/C- 225: Anti-EGFR Extracellular domain (632 amino acids) Ligand-binding site Transmembrane domain (22 amino acids) Intracellular domain (580 amino acids) Tyrosine kinase activity