"When a tumor develops angiogenic ability, it is probably the defining moment when it goes from being a local or precancerous lesion to a truly malignant or metastatic lesion", said Dr. G. Neal Mauldin, DVM, Dipl. ACVIM.
Some cancer drugs work by inhibiting the blood flow into cancer cells that helps
them grow. These drugs are called anti-angiogenesis agents, or angiogenesis
inhibitors (AI's).
Once researchers learned that cancer cells could release molecules that help
activate the process of angiogenesis, the challenge became to find and study these
angiogenesis-stimulating molecules in animal and human tumors.
Through such studies more than a dozen different proteins, as well as several
smaller molecules, have been identified as angiogenic.
Protein molecules that are important for sustaining tumor growth
- Vascular Endothelial Growth Factor (VEGF) and
- Basic Fibroblast Growth Factor (bFGF)
- Epidermal growth factor (EGF)
- Tumor necrosis factor alpha (TNF-alpha), and at least a few dozen others
It is important to remember that VEGF and bFGF are produced by many kinds of
cancer cells but also by certain types of normal cells.
How do new blood vessels form to feed cancer?
1. Tumor angiogenesis begins when cancerous tumor cells release molecules of
VEGF and bFGF into the surrounding tissue. When they encounter endothelial cells,
the molecules bind to specific proteins, called receptors that sit on the outer
surface of the cells.
The binding of either VEGF or bFGF to its appropriate receptor activates a series of
relay proteins that transmit signals into the nucleus of the endothelial cells.
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2. The nuclear signal
prompts the activity of
a group of genes.
3. These genes
produce proteins needed
for new endothelial cell
growth.
4. Eventually, new
blood vessel growth
occurs. |
Image courtesy of the National Cancer Institute |
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Blocking Angiogenesis
There are several different approaches to blocking angiogenesis:
- Inhibiting release of angiogenic factors from the tumor
- Neutralizing them after release or
- Inhibiting endothelial cells from responding to them
When angiogenesis is blocked, tumor capillaries actually regress; consequently,
the tumor itself regresses due to oxygen and nutrient deprivation or starvation.
Anti-angiogenic therapy could be used in conjunction with surgical removal of a
primary tumor, and would be directed against occult or overt metastasis to shrink
a localized tumor, facilitating definitive surgery, radiation or chemotherapy as
curative treatments.
