1. What is angiogenesis?

Angiogenesis is the formation of new blood vessels. Angiogenesis is a process controlled by certain chemicals produced in the body. Some of these chemicals stimulate cells to repair damaged blood vessels or form new ones. Other chemicals, called angiogenesis inhibitors, signal the process to stop.

2. Why is angiogenesis important in cancer?

Angiogenesis plays an important role in the growth and spread of cancer. New blood vessels “feed” the cancer cells with oxygen and nutrients, allowing these cells to grow, invade nearby tissue, spread to other parts of the body, and form new colonies of cancer cells.

3. How can angiogenesis be stopped in tumors?

Because tumors cannot grow or spread without the formation of new blood vessels, scientists are trying to find ways to stop angiogenesis. They are studying natural and synthetic angiogenesis inhibitors, also called antiangiogenic agents, in the hope that these chemicals will prevent or slow down the growth of cancer by blocking the formation of new blood vessels.

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 (Avastin®) for use with other drugs to treat colorectal cancer that has spread to other parts of the body, some non-small cell lung cancers, and some breast cancers that have spread to other parts of the body. Bevacizumab was the first angiogenesis inhibitor proven to delay tumor growth and, more importantly, extend the lives of patients.

The FDA has also approved other drugs with antiangiogenic activity as cancer therapies for multiple myeloma, mantle cell lymphoma, gastrointestinal stromal tumors (GIST), and kidney cancer.

Researchers are also exploring the use of these drugs to treat other cancers (see Question 8).

5. What are the advantages of angiogenesis inhibitors?

Angiogenesis inhibitors usually have only mild side effects and are not toxic to most healthy cells. Tumors do not seem to develop a resistance to angiogenesis inhibitors, even when given over a long period of time, unlike the resistance seen when chemotherapy drugs are used.

Angiogenesis inhibitors seem to help some chemotherapy drugs and radiation therapy work more effectively when given in combination.

6. What are the limitations of angiogenesis inhibitors?

Angiogenesis inhibitor therapy may not necessarily kill tumors, but instead may keep tumors stable. Therefore, this type of therapy may need to be administered over a long period. Because angiogenesis is important in wound healing and in reproduction, long-term treatment with antiangiogenic agents could cause problems with bleeding, blood clotting, heart function, the immune system, and the reproductive system (1).

7. Does angiogenesis inhibitor therapy have any complications or side effects?

A patient’s immune system may be compromised, making the patient more susceptible to infection and causing wounds to heal poorly, if at all. Patients may experience reproductive problems, and damage to the fetus is likely if a patient becomes pregnant while taking the antiangiogenic drug. Heart problems and high blood pressure could be made worse, and bleeding or blood clots could increase (1).

Since angiogenesis inhibitor therapy is still under investigation, all of the possible complications and side effects are still unknown.

8. What does the future hold for angiogenesis inhibitor therapy?

Other angiogenesis inhibitors are currently being tested in clinical trials (research studies) but have not yet been shown to be effective against cancer in humans. If these angiogenesis inhibitors are proven to be both safe and effective in treating human cancer, they may be approved by the FDA and made available for widespread use.

The list below includes cancers that are being studied in active phase III treatment clinical trials using angiogenesis inhibitors. The clinical trials are in the National Cancer Institute’s (NCI) clinical trials database at http://www.cancer.gov/clinicaltrials/search on the Internet. For information about how to search the database, see “Help Using the Basic Clinical Trial Search Form” at http://www.cancer.gov/clinicaltrials/basic-search-form-help on the Internet.


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

• Breast cancer ¹
• Esophageal cancer ²
• Gastrointestinal Stromal Tumors (GIST) ³
• Kidney (renal cell) cancer ⁴
• Leukemia ⁵
• Liver (adult primary) cancer ⁶
• Lymphoma ⁷
• Melanoma ⁸
• Multiple myeloma ⁹
• Non-small cell lung cancer (NSCLC) ¹⁰
• Ovarian epithelial cancer ¹¹
• Pancreatic cancer ¹²
• Prostate cancer ¹³
• Stomach (gastric) cancer ¹⁴

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 Reference

1. Cohen MH, Gootenberg J, Keegan P, Pazdur R. FDA drug approval summary: Bevacizumab plus FOLFOX4 as second-line treatment of colorectal cancer. The Oncologist 2007; 12(3):356–361.
   

Related NCI materials and Web pages:

• National Cancer Institute Fact Sheet 2.11, Clinical Trials: Questions and Answers ¹⁵
  (http://www.cancer.gov/cancertopics/factsheet/Information/clinical-trials)
• National Cancer Institute Fact Sheet 6.7, Cancer: Questions and Answers ¹⁶
  (http://www.cancer.gov/cancertopics/factsheet/Sites-Types/general)
• National Cancer Institute Fact Sheet 7.2, Biological Therapies for Cancer: Questions and Answers ¹⁷
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/biological)
• National Cancer Institute Fact Sheet 7.49, Targeted Cancer Therapies: Questions and Answers ¹⁸
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/targeted)
• What You Need To Know About™ Cancer ¹⁹
  (http://www.cancer.gov/cancertopics/wyntk/overview)

NCI’s Cancer Information Service
Telephone (toll-free): 1–800–4–CANCER (1–800–422–6237)
TTY (toll-free): 1–800–332–8615
LiveHelp^® online chat: https://cissecure.nci.nih.gov/livehelp/welcome.asp

Glossary Terms

Blood vessel formation. Tumor angiogenesis is the growth of new blood vessels that tumors need to grow. This is caused by the release of chemicals by the tumor.

A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor may prevent the growth of new blood vessels that tumors need to grow.

Having to do with reducing the growth of new blood vessels.

A monoclonal antibody used in the treatment of colorectal cancer that has spread. 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. Also called bevacizumab.

A monoclonal antibody used in the treatment of colorectal cancer that has spread. 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. Also called Avastin.

A tube through which the blood circulates in the body. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Treatment with drugs that kill cancer cells.

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.

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).

To heal or restore health; a treatment to restore health.

The developing offspring from 7 to 8 weeks after conception until birth.

An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The Food and Drug Administration also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called FDA.

The complex group of organs and cells that defends the body against infections and other diseases.

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

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.

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.

The organs involved in producing offspring. In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). In men, it includes the prostate, the testes, and the penis.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

A group or layer of cells that work together to perform a specific function.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

A break in the skin or other body tissues caused by injury or surgical incision (cut).