template

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The Endothelin AxisOncogenic Mechanisms
ET-1
ETAR
Ras
Plasma membrane
PLC
G-protein
Raf
Ins P3
DAG
PKC
ET-1 acting via ETAR promotes
Ca2 release
MAPK

• Cell growth
• Inhibition of apoptosis
• Angiogenesis
• Osteoblastic remodeling
• Nociceptive pain response

Nucleus
Modified from Bagnato A, Catt KJ. Trends Endocr
Metab. 19989(9)378383.
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Mechanism of action
ETA receptor
ETB receptor
ET-1
Cancercell
Neutralendopeptidase 24.11
NEP
NEP
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Tumour angiogenesis promotes tumor growth and
metastasis

• The creation of new vessels and lymphatic tissue
  by tumors allows them to enlarge and to
  metastasize
• Inhibition of tumour angiogenesis has the
  potential to inhibit tumor growth and spread

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Anti-angiogenic Agents

HIF
mTOR
Bevacizumab
CCI 779
VEGF
PDGF
VEGFR
EGFR
PDGFR
Raf
Raf
Sorafenib
Erlotinib
Sunitinib
AG-013736
Sorafenib
Sorafenib
mTOR mammalian target of rapamycin
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Stem Cell Targeted Therapy

• True PCa stem-cell phenotype not yet identified,
  however,
• several stem-cell targets overexpressed in PCa
• hedgehog signaling pathway, human telomerase, and
  CD133

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New concepts neededfor new challenges
Think differently
20th century Seek and destroy 21st
century Target and control
Andrew von Eschenbach Director of theNational
Cancer Institute
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The HRPC - Team
Urologist
Medical oncologist
Pain specialist
Radiation oncologist
Neurosurgeon
Support group
Psychologist
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No real breakthrough yet in terms of survival !!
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BRIDGING THE WORLD
Eau Europa Uomo
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I appreciate your attention Vielen Dank!