Angiostatic Approach to Cancer Therapy

Various inhibitors of angiogenesis are under investigation in patients with
advanced cancer:


Drugs that block matrix breakdown:
1. Marimastat

against
pancreas,
non-small
cell lung,
breast
cancers
Synthetic inhibitor of
matrix
metalloproteinases
(MMPs)
2. Bay 12-9566

against lung,
ovary, and
pancreatic
cancers
Synthetic inhibitor of
tumor growth
3. AG3340

against
non-small
cell lung;
against
prostate
cancer
Synthetic MMP
inhibitor



4. CGS
27023A

Synthetic MMP inhibitor
5. COL-3

Synthetic MMP
inihibitor.
Tetracycline derivative
6. Neovastat

against
non-small
cell lung
cancer
Naturally occurring
MMP inhibitor
7. BMS-275291

Synthetic MMP
Inhibitor
8. Dalteparin
9. Suramin



Drugs that inhibit endothelial cells directly:

1. TNP-470

against
advanced
cancer for
adults with
solid tumors;
against
pediatric solid
tumors,
lymphomas,
and acute
leukemias
Synthetic
analogue of
fumagillin; inhibits
endothelial cell
growth
2. Thalidomide

against
Kaposi's
sarcoma,
glioblastoma,
prostate, lung,
and breast
cancers
Mech. unknown
3. Squalamine

Extract from
dogfish shark liver;
inhibits
sodium-hydrogen
exchanger, NHE3
4. Combretastatin

Induction of
apoptosis in
proliferating
endothelial cells
5. Endostatin

solid
tumor
Inhibition of
endothelial cells

6. 2-methoxyestradiol
(2-ME)
7. CC-5013 (Thalidomide Analog)
8. LY317615 (Protein Kinase C Beta Inhibitor)
9.Soy Isoflavone (Genistein; Soy Protein Isolate)

Drugs that block activators of angiogenesis:

1. Anti-VEGF Antibody
against lung,
breast,
prostate,
colorectal, and
renal cancers
Monoclonal
antibody to
vascular
endothelial
growth factor
(VEGF)



2. SU5416

against
Kaposi's
sarcoma,
against
metastatic
colorectal
cancer, and
against
advanced
malignancies
Blocks VEGF
receptor
signaling
3. SU6668

against
advanced
tumors
Blocks VEGF,
FGF, and EGF
receptor
signaling





4. PTK787/ZK
22584

against
advanced
cancers
against
glioblastoma
and Kaposi's
sarcoma;
against Von
Hippel Lindau
disease
Blocks VEGF
receptor
signaling
5. Interferon-alpha
Commercially
Available

Inhibition of
bFGF and
VEGF
production



Drugs that inhibit endothelial-specific integrin/survival signaling:

1. Vitaxin

Antibody to
integrin present
on endothelial
cell surface
2. EMD121974

against Kaposi's
sarcoma, brain
tumors, and
solid tumors
Small molecule
blocker of integrin
present on
endothelial cell
surface

Drugs with non-specific mechanism of action:
1. CAI

against ovarian,
non-small cell
lung, and renal
cell cancers
Inhibitor of
calcium influx
2. Interleukin-12
against Kaposi's
sarcoma and
solid tumors
Up-regulation of
interferon gamma
and IP-10
3. IM862
Against AIDS-related
Kaposi's
sarcoma
Unknown
mechanism

Antiangiogenic therapy combined with conventional anticancer therapies may represent an useful tool in the future care of patients with cancer.