Angiogenesis is the formation of new blood vessels. This process is normal in the growth and development of children, but happens less often in adults. For example, angiogenesis occurs during the healing of a deep cut or in the lining of the uterus in a woman after the menstrual cycle. Otherwise, angiogenesis in adults is usually part of a disease process such as cancer.

Angiogenesis is essential for the growth and metastasis (spread) of cancer. A growing tumor requires nutrients and oxygen, which helps it grow, invade nearby tissues, and metastasize. To reach these nutrients, the tumor builds new blood vessels. In fact, growing tumors can become inactive if they can't find a new supply of nutrients.

Because angiogenesis is necessary in the growth and spread of cancer, each part of the angiogenesis process is a potential target for new cancer therapies. The assumption is that if a drug can stop the tumor from receiving the supply of nutrients, the tumor will "starve" and die. Drugs that stop angiogenesis have become an important part of cancer treatment for many types of cancer.

Contributors to angiogenesis

In cancer, angiogenesis begins when cancer cells produce a variety of growth factors (substances that regulate cell division and cell survival) and other biologic molecules. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) are important activators of angiogenesis. These growth factors attach to special proteins on the outside of cancer cells called receptors. A receptor acts like a doorway to the cell, and this action starts a series of chemical reactions inside the cell. Because VEGF is so important to angiogenesis, its receptor was one of the first targets of new cancer treatments. In addition to VEGF and PDGF, researchers have identified other contributors to angiogenesis, and these are being explored as potential targets for new cancer treatments.

Current cancer treatments that block angiogenesis

Drugs that are designed to stop angiogenesis are called angiogenesis inhibitors or antiangiogenesis drugs. Typically, these drugs are given with other types of treatment, such as chemotherapy. The following drugs are examples of angiogenesis inhibitors used to treat cancer. Additional drugs are being evaluated in clinical trials to treat a variety of cancers. Talk with your doctor for more information about these and other cancer drugs.

• Thalidomide (Thalomid), a pill that is taken by mouth, appears to stop endothelial cells (cells that line blood vessels) from forming new blood vessels and is a treatment for multiple myeloma and other types of cancer. However, it is harmful to fetuses, so women who are pregnant or plan to become pregnant should not take thalidomide.
  
  
• Lenalidomide (Revlimid), a drug that is similar to thalidomide, is also used to treat multiple myeloma and a specific type of myelodysplastic syndrome (MDS). This drug is a pill that is taken by mouth, and it is a risk to pregnant women and their unborn babies.
  
  
• Bevacizumab (Avastin) is a monoclonal antibody, a substance produced in the laboratory that attaches to VEGF receptors on cancer cells. This drug is used to treat many types of cancer including colorectal cancer, kidney cancer, breast cancer, and lung cancer. Bevacizumab is given as an injection.
  
  
• Sunitinib (Sutent) blocks both the VEGF and PDGF receptors and is used to treat kidney cancer and gastrointestinal stromal tumor (GIST). It is also being evaluated for use in other types of cancer. It is a pill that is taken by mouth.
  
  
• Sorafenib (Nexavar) blocks angiogenesis in multiple ways, including the VEGF and PDGF receptors and other specialized proteins in the cancer cell. It is also a pill taken by mouth and is used to treat kidney and liver cancers.

Side effects of angiogenesis inhibitors

Because these drugs act on parts of the blood and blood vessels, they tend to have side effects that affect these processes. For example, many angiogenesis inhibitors raise a person’s blood pressure, which can be serious, but it is treatable with medication. Rarely, these medications may cause serious bleeding, heart attacks, heart failure, or blood clots. People at higher risk for these conditions should discuss the risks and benefits of these treatments and ways to monitor these risks. (For example, patients who have had chemotherapy with a class of drugs called anthracyclines or radiation therapy to the chest wall, have a higher risk of congestive heart failure with bevacizumab.) Other side effects of these drugs may include a rash and/or dry, itchy skin, hand-foot syndrome (tender, thickened areas on the skin, sometimes with blisters on palms and soles), diarrhea, fatigue, and low blood counts. Angiogenesis inhibitors can also interfere with wound healing and cause cuts to re-open or bleed. Rarely, perforations (holes) in the intestines can occur. These are called bowel perforations and usually require surgery to correct. Although some side effects may be common, they do not happen with every drug or with every person.

More Information

Cancer.Net Feature: Understanding Targeted Treatments

Skin Reactions to Targeted Therapies

Managing Side Effects

Additional Resources

National Cancer Institute: Angiogenesis Inhibitors Therapy: Questions and Answers