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Angiogenesis Inhibitors

Angiogenesis Inhibitors


Angiogenesis is a term that means new blood vessel formation. This is a normal process in everyone, but the rate of angiogenesis increases in cancer, since cancer needs blood vessels in order to grow and spread. Angiogensis Inhibitors prevent, slow down, or block the growth of new blood vessels.

A significant physiologic difference between normal tissue and cancer tissue is blood supply. Some tumors can induce new growth of blood vessels (angiogenesis) which enables expansion of the primary tumor by providing nutrients and oxygen through the blood supply to new tumor cells. The abnormal increase in angiogenesis in tumors allows for the formation of blood vessels with incomplete endothelial basement membrane, leading to leaky vessels and allowing tumor cells in to access the general blood circulation. This is a factor implicated in the metastasis of cancer cells.


Image courtesy of the Institute for Biomedical Technologies ITB - CNR


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"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.


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


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.





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