Hypoxia,
EGFR signaling
VEGF
P
ericyte
recr
uitment
Necrotic
core
T
umor
rim
T
umor
cells
PDGF
a
c
V
ascular disr
uption
d
Hypoxia,
EGFR signaling
VEGF
P
ericyte
recr
uitment
Necrotic
core
T
umor
rim
T
umor
cells
PDGF
a
c
V
ascular disr
uption
d
Hypoxia,
EGFR signaling
VEGF
P
ericyte
recr
uitment
T
umor
cells
PDGF
a
c
Abnormal Tumor VascularNetwork with Poor Perfusion,High Interstitial Fluid Pressureand Areas of Hypoxia
Necrotic Central Core
Decreased Nascent Vessel Number
Improved blood flow leading to improved delivery of chemotherapeutic agents
Abnormal Bulges
Blind Ends
Remaining rim of viable cells that can be targeted with chemotherapeutic agents and radiation
Small Molecules: e.g., DMXAA, NPI-2358Ligand-based: e.g., antibody-toxin, antibody-IL12, ‘naked’ antibodies, VEGF-gelonin
Direct Endothelial Cell EffectsVascular Disruption
Anti-VEGF EffectsInitial Vascular Normalization
Anti-Angiogenic Agents
P
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