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Angiogenesis and Anti-angiogenesis Drugs

Although progress has been made in the early detection of cancer, and in improved treatment options once cancer is diagnosed, there are still many cancers, including mesothelioma, which can not be cured and remain difficult to treat effectively. In recent years, researchers have learned a great deal about how cancer cells differ from normal cells and, in an effort to find drugs without the potentially severe side effects of chemotherapy, have now discovered drugs which target the tumor itself while sparing the body’s normal cells. One such group are the anti-angiogenesis drugs.

What is angiogenesis?

The term “angiogenesis” refers to the formation of new blood vessels. During the human growth process, the body needs new blood vessels to supply blood to all the cells of the body, however in someone with cancer, this identical process creates blood vessels that supply the tumor with the oxygen and nutrients it needs to grow, spread and establish new colonies of cancer cells.

Why do tumors require their own blood supply?

A tumor begins as a single cell that becomes “malignant” and then goes on to rapidly divide, forming multiple cancer cells. Early on, these cells use nearby blood vessels to supply nourishment, but as the tumor grows, some cells may be further from the blood supply. In order to continue tumor growth, new blood vessels must be formed.

What is anti-angiogenesis treatment?

Anti-angiogenesis is a targeted therapy using drugs or other substances to prevent tumors from creating new blood vessels, thus, stopping the growth of the tumor. Researchers are currently studying both natural and synthetic anti-angiogenesis inhibitors, and although many of these drugs are still available only in clinical trials, the first anti-angiogenesis drug, bevacizumab (Avastin), was approved by the Food and Drug Administration in February, 2004, for use in the treatment of metastatic colon cancer. A Phase II clinical trial of cisplatin, pemetrexed and bevacizumab for untreated mesothelioma and a Phase II trial of bevacizumab and erlotinib for previously treated mesothelioma are ongoing, and trials of other anti-angiogenesis agents are being tested in mesothelioma as well.

How do anti-angiogenesis drugs work?

Anti-angiogenesis drugs do not directly attack cancer cells, but target the blood supply necessary for survival and growth of the tumor. In this way, they may prevent new tumors from forming, and cause existing tumors to shrink.

One of the most important proteins in the growth of new blood vessels is called vascular endothelial growth factor or VEGF, which is secreted by some cancer cells. It appears that VEGF plays an important role in the growth of mesothelioma. VEGF attaches to a protein, or VEGF receptor, on the surface of nearby endothelial cells, and then signals the cell’s control centers to begin growth and formation of new blood vessels. Many of the anti-angiogensis drugs currently being tested attack this VEGF pathway, including bevacizumab (Avastin) which is a synthetic version of an immune system protein that binds to VEGF and prevents it from reaching the VEGF receptor. Other drugs, such as sorafenib (Nexavar) are small molecules that attach directly to the VEGF receptor and prevent it from being activated.

How is anti-angiogenesis treatment different from traditional chemotherapy?

Traditional chemotherapy drugs work by attacking cells in the body that divide rapidly. Unfortunately, some normal cells such as those in the mouth or the digestive system, also divide rapidly and can not be differentiated from malignant cells. This can lead to side effects including mouth sores, nausea and diarrhea. Anti-angiogenesis drugs do not target normal cells, so in many cases, side effects are milder. They can have their own side effects however, and because many drugs are still being evaluated in the clinical trial system, it is not yet known whether side effects will be similar for all drugs in this class. If enrolling in a clinical trial that involves anti-angiogenesis drugs, your doctor will explain what side effects may be encountered.

Are anti-angiogenesis drugs ever combined with other chemotherapy drugs?

There is some reason to believe that standard chemotherapy drugs and anti-angiogenesis drugs may work well in combination. In early clinical trials of bevacizumab (Avastin), it was determined that bevacizumab alone did not help cancer patients live longer. In subsequent studies, however, it was found that when combined with other chemotherapy drugs it was more effective.

Is continued research being done on anti-angiogenesis drugs?

In the clinical trial system, there are currently hundreds of anti-angiogenesis drugs being studied. Some of these drugs are being tested as single agents, while others are being used in combination with other treatments. Drugs that are in the early stages of trials (see Trial Phases in the Clinical Trial section) often carry a letter and/or number designation, while those in later trials may be listed by name. There are several trials of anti-angiogenesis drugs now enrolling patients with malignant mesothelioma.

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Clincial trials of anti-angiogenesis agents for mesothelioma.