Questions About Cancer? 1-800-4-CANCER
National Cancer Institute Fact Sheet
  • Reviewed: 10/07/2011

Angiogenesis Inhibitors

Key Points

  • Angiogenesis is the formation of new blood vessels. Tumors need blood vessels to grow and spread.
  • Angiogenesis inhibitors are designed to prevent the formation of new blood vessels, thereby stopping or slowing the growth or spread of tumors.
  • The U.S. Food and Drug Administration has approved several angiogenesis inhibitors for the treatment of cancer.
  • Angiogenesis inhibitors may have side effects that are different from those of other cancer treatments. In addition, they may only stop or slow the growth of a cancer, not completely eradicate it.

  1. What is angiogenesis?

    Angiogenesis is the formation of new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells, which line the inside wall of blood vessels.

    The process of angiogenesis is controlled by chemical signals in the body. These signals can stimulate both the repair of damaged blood vessels and the formation of new blood vessels. Other chemical signals, called angiogenesis inhibitors, interfere with blood vessel formation. Normally, the stimulating and inhibiting effects of these chemical signals are balanced so that blood vessels form only when and where they are needed.

  2. Why is angiogenesis important in cancer?

    Angiogenesis plays a critical role in the growth and spread of cancer. A blood supply is necessary for tumors to grow beyond a few millimeters in size. Tumors can cause this blood supply to form by giving off chemical signals that stimulate angiogenesis. Tumors can also stimulate nearby normal cells to produce angiogenesis signaling molecules. The resulting new blood vessels “feed” growing tumors with oxygen and nutrients, allowing the cancer cells to invade nearby tissue, to move throughout the body, and to form new colonies of cancer cells, called metastases.

    Because tumors cannot grow beyond a certain size or spread without a blood supply, scientists are trying to find ways to block tumor angiogenesis. They are studying natural and synthetic angiogenesis inhibitors, also called antiangiogenic agents, with the idea that these molecules will prevent or slow the growth of cancer.

  3. How do angiogenesis inhibitors work?

    Angiogenesis requires the binding of signaling molecules, such as vascular endothelial growth factor (VEGF), to receptors on the surface of normal endothelial cells. When VEGF and other endothelial growth factors bind to their receptors on endothelial cells, signals within these cells are initiated that promote the growth and survival of new blood vessels.

    Angiogenesis inhibitors interfere with various steps in this process. For example, bevacizumab (Avastin®) is a monoclonal antibody that specifically recognizes and binds to VEGF (1). When VEGF is attached to bevacizumab, it is unable to activate the VEGF receptor. Other angiogenesis inhibitors, including sorafenib and sunitinib, bind to receptors on the surface of endothelial cells or to other proteins in the downstream signaling pathways, blocking their activities (2).

  4. Are any angiogenesis inhibitors currently being used to treat cancer in humans?

    Yes. The U.S. Food and Drug Administration (FDA) has approved bevacizumab to be used alone for glioblastoma that has not improved with other treatments and to be used in combination with other drugs to treat metastatic colorectal cancer, some non-small cell lung cancers, and metastatic renal cell cancer. Bevacizumab was the first angiogenesis inhibitor that was shown to slow tumor growth and, more important, to extend the lives of patients with some cancers.

    The FDA has approved other drugs that have antiangiogenic activity, including sorafenib (Nexavar®), sunitinib (Sutent®), pazopanib (Votrient®), and everolimus (Afinitor®). Sorafenib is approved for hepatocellular carcinoma and kidney cancer, sunitinib and everolimus for both kidney cancer and neuroendocrine tumors, and pazopanib for kidney cancer. Researchers are exploring the use of angiogenesis inhibitors to treat other types of cancer (see Question 7). In addition, angiogenesis inhibitors are being used to treat some diseases that involve the development of abnormal blood vessel growth in noncancer conditions, such as macular degeneration.

  5. How are angiogenesis inhibitors different from conventional anticancer drugs?

    Angiogenesis inhibitors are unique cancer-fighting agents because they tend to inhibit the growth of blood vessels rather than tumor cells. In some cancers, angiogenesis inhibitors are most effective when combined with additional therapies, especially chemotherapy. It has been hypothesized that these drugs help normalize the blood vessels that supply the tumor, facilitating the delivery of other anticancer agents, but this possibility is still being investigated.

    Angiogenesis inhibitor therapy does not necessarily kill tumors but instead may prevent tumors from growing. Therefore, this type of therapy may need to be administered over a long period.

  6. Do angiogenesis inhibitors have side effects?

    Initially, it was thought that angiogenesis inhibitors would have mild side effects, but more recent studies have revealed the potential for complications that reflect the importance of angiogenesis in many normal body processes, such as wound healing, heart and kidney function, fetal development, and reproduction. Side effects of treatment with angiogenesis inhibitors can include problems with bleeding, clots in the arteries (with resultant stroke or heart attack), hypertension, and protein in the urine (3–5). Gastrointestinal perforation and fistulas also appear to be rare side effects of some angiogenesis inhibitors. Animal studies have revealed the potential for birth defects, although there is no clinical evidence for such effects in humans.

    It is likely that some of the possible complications of angiogenesis inhibitor therapy remain unknown. As more patients are treated with these agents, doctors will learn more about possible rare side effects.

  7. What is the ongoing research on angiogenesis inhibitors?

    In addition to the angiogenesis inhibitors that have already been approved by the FDA, others that target VEGF or other angiogenesis pathways are currently being tested in clinical trials (research studies involving patients). If these angiogenesis inhibitors prove to be both safe and effective in treating human cancer, they may be approved by the FDA and made available for widespread use.

    In addition, phase I and II clinical trials are testing the possibility of combining angiogenesis inhibitor therapy with other treatments that target blood vessels, such as tumor-vascular disrupting agents, which damage existing tumor blood vessels (6).

    The list below includes cancers that are being studied in active phase III treatment clinical trials using angiogenesis inhibitors. The clinical trials can be found in NCI’s list of clinical trials 1. For information about how to search the list, see “Help Using the NCI Clinical Trials Search Form 2.”

    Types of Cancer in Active Phase III Treatment Clinical Trials of Angiogenesis Inhibitors:

    For more information about NCI’s clinical trials database and other cancer-related information, call NCI’s Cancer Information Service at 1–800–4–CANCER (1–800–422–6237).

Selected References
  1. Shih T, Lindley C. Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clinical Therapeutics 2006; 28(11):1779–1802. [PubMed Abstract] 16
  2. Gotink KJ, Verheul HM. Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? Angiogenesis 2010; 13(1):1–14. [PubMed Abstract] 17
  3. Cook KM, Figg WD. Angiogenesis inhibitors: current strategies and future prospects. CA: A Cancer Journal for Clinicians 2010; 60(4):222–243. [PubMed Abstract] 18
  4. Chen HX, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nature Reviews Clinical Oncology 2009; 6(8):465–477. [PubMed Abstract] 19
  5. Verheul HM, Pinedo HM. Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition. Nature Reviews Cancer 2007; 7(6):475–485. [PubMed Abstract] 20
  6. Siemann DW. The unique characteristics of tumor vasculature and preclinical evidence for its selective disruption by Tumor-Vascular Disrupting Agents. Cancer Treatment Reviews 2011; 37(1):63–74. [PubMed Abstract] 21
Related Resources


Glossary Terms

Afinitor (uh-FIH-nih-tor)
A drug used to treat certain types of pancreatic cancer. It is also used to treat a type of advanced kidney cancer and to treat subependymal giant cell astrocytoma in some patients. It is being studied in the treatment of other types of cancer and other conditions. Afinitor stops cancer cells from dividing and may prevent the growth of new blood vessels that tumors need to grow. It also lowers the body’s immune response. It is a type of kinase inhibitor, a type of angiogenesis inhibitor, and a type of immunosuppressant. Also called everolimus and RAD001.
antiangiogenic (AN-tee-AN-jee-oh-JEH-nik)
Having to do with reducing the growth of new blood vessels.
Avastin (uh-VAS-tin)
A drug used to treat several types of cancer, including certain types of colorectal, lung, breast, and kidney cancers and glioblastoma. It is also being studied in the treatment of other types of cancer. Avastin binds to vascular endothelial growth factor (VEGF) and may prevent the growth of new blood vessels that tumors need to grow. It is a type of antiangiogenesis agent and a type of monoclonal antibody. Also called bevacizumab.
bevacizumab (beh-vuh-SIH-zoo-mab)
A drug used to treat several types of cancer, including certain types of colorectal, lung, breast, and kidney cancers and glioblastoma. It is also being studied in the treatment of other types of cancer. Bevacizumab binds to vascular endothelial growth factor (VEGF) and may prevent the growth of new blood vessels that tumors need to grow. It is a type of antiangiogenesis agent and a type of monoclonal antibody. Also called Avastin.
clinical trial (KLIH-nih-kul TRY-ul)
A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.
colorectal cancer (KOH-loh-REK-tul KAN-ser)
Cancer that develops in the colon (the longest part of the large intestine) and/or the rectum (the last several inches of the large intestine before the anus).
endothelial cell (EN-doh-THEE-lee-ul sel)
The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart.
everolimus (eh-veh-ROH-lih-mus)
A drug used to treat certain types of pancreatic cancer. It is also used to treat a type of advanced kidney cancer and to treat subependymal giant cell astrocytoma in some patients. It is being studied in the treatment of other types of cancer and other conditions. Everolimus stops cancer cells from dividing and may prevent the growth of new blood vessels that tumors need to grow. It also lowers the body’s immune response. It is a type of kinase inhibitor, a type of angiogenesis inhibitor, and a type of immunosuppressant. Also called Afinitor and RAD001.
fistula (FIS-chuh-luh)
An abnormal opening or passage between two organs or between an organ and the surface of the body. Fistulas may be caused by injury, infection, or inflammation, or may be created during surgery.
glioblastoma (GLEE-oh-blas-TOH-muh)
A fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma usually occurs in adults and affects the brain more often than the spinal cord. Also called GBM, glioblastoma multiforme, and grade IV astrocytoma.
macular degeneration (MA-kyoo-ler dee-JEH-neh-RAY-shun)
A condition in which there is a slow breakdown of cells in the center of the retina (the light-sensitive layers of nerve tissue at the back of the eye). This blocks vision in the center of the eye and can cause problems with activities such as reading and driving. Macular degeneration is most often seen in people who are over the age of 50. Also called age-related macular degeneration, AMD, and ARMD.
monoclonal antibody (MAH-noh-KLOH-nul AN-tee-BAH-dee)
A type of protein made in the laboratory that can bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.
Nexavar (NEK-suh-var)
A drug used to treat advanced kidney cancer and a type of liver cancer that cannot be removed by surgery. It is also being studied in the treatment of other types of cancer. Nexavar stops cells from dividing and may prevent the growth of new blood vessels that tumors need to grow. It is a type of kinase inhibitor and a type of antiangiogenesis agent. Also called BAY 43-9006, sorafenib, and sorafenib tosylate.
non-small cell lung cancer (... sel lung KAN-ser)
A group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope. The three main types of non-small cell lung cancer are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Non-small cell lung cancer is the most common kind of lung cancer.
nutrient (NOO-tree-ent)
A chemical compound (such as protein, fat, carbohydrate, vitamin, or mineral) contained in foods. These compounds are used by the body to function and grow.
pazopanib hydrochloride (puh-ZOH-puh-nib HY-droh-KLOR-ide)
A drug that is used to treat kidney cancer and is being studied in the treatment of other types of cancer. It may prevent the growth of new blood vessels that tumors need to grow. It is a type of protein tyrosine kinase inhibitor and a type of antiangiogenesis agent. Also called GW786034 and Votrient.
phase I trial (fayz … TRY-ul)
The first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection) and the best dose. The dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments.
phase II trial (fayz … TRY-ul)
A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.
phase III trial (fayz … TRY-ul)
A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.
renal cell cancer (REE-nul sel KAN-ser)
The most common type of kidney cancer. It begins in the lining of the renal tubules in the kidney. The renal tubules filter the blood and produce urine. Also called hypernephroma, renal cell adenocarcinoma, and renal cell carcinoma.
sorafenib (sor-A-feh-nib)
A drug used to treat advanced kidney cancer and a type of liver cancer that cannot be removed by surgery. It is also being studied in the treatment of other types of cancer. Sorafenib stops cells from dividing and may prevent the growth of new blood vessels that tumors need to grow. It is a type of kinase inhibitor and a type of antiangiogenesis agent. Also called BAY 43-9006, Nexavar, and sorafenib tosylate.
sunitinib (soo-NIH-tih-nib)
A drug used to treat certain types of pancreatic cancer. It is also used to treat gastrointestinal stromal tumors (GIST) in some patients and to treat advanced kidney cancer. It is being studied in the treatment of other types of cancer. Sunitinib stops cancer cells from dividing and may prevent the growth of new blood vessels that tumors need to grow. It is a type of tyrosine kinase inhibitor and a type of angiogenesis inhibitor. Also called SU011248, SU11248, sunitinib malate, and Sutent.
Sutent (SOO-tent)
A drug used to treat certain types of pancreatic cancer. It is also used to treat gastrointestinal stromal tumors (GIST) in some patients and to treat advanced kidney cancer. It is being studied in the treatment of other types of cancer. Sutent stops cancer cells from dividing and may prevent the growth of new blood vessels that tumors need to grow. It is a type of tyrosine kinase inhibitor and a type of angiogenesis inhibitor. Also called SU011248, SU11248, sunitinib, and sunitinib malate.
tissue (TIH-shoo)
A group or layer of cells that work together to perform a specific function.
Votrient (VOH-tree-ent)
A drug that is used to treat kidney cancer and is being studied in the treatment of other types of cancer. It may prevent the growth of new blood vessels that tumors need to grow. It is a type of protein tyrosine kinase inhibitor and a type of antiangiogenesis agent. Also called GW786034 and pazopanib hydrochloride.
wound (woond)
A break in the skin or other body tissues caused by injury or surgical incision (cut).

Table of Links

1http://www.cancer.gov/clinicaltrials/search
2http://www.cancer.gov/clinicaltrials/search-form-help
3http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586362
4http://www.cancer.gov/clinicaltrials/search/results?protocolsearchid=8706973
5http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586399
6http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586407
7http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586416
8http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586421
9http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586451
10http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586448
11http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586453
12http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=745438
5&vers=1
13http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586434
14http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586442
15http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=4586439
16http://www.ncbi.nlm.nih.gov/pubmed/17212999
17http://www.ncbi.nlm.nih.gov/pubmed/20012482
18http://www.ncbi.nlm.nih.gov/pubmed/20554717
19http://www.ncbi.nlm.nih.gov/pubmed/19581909
20http://www.ncbi.nlm.nih.gov/pubmed/17522716
21http://www.ncbi.nlm.nih.gov/pubmed/20570444
22http://www.cancer.gov/cancertopics/factsheet/Therapy/biological
23http://www.cancer.gov/cancertopics/factsheet/Information/clinical-trials
24http://www.cancer.gov/cancertopics/factsheet/Therapy/targeted
25http://www.cancer.gov/cancertopics/wyntk/cancer