The development of monoclonal antibodies to target specific sites on cancer cells is poised to revolutionize the way cancer will be treated in the coming years. Monoclonal antibodies have been called "magic bullets" because they target specific proteins on the surface of only cancer cells, leaving untouched those cells that do not have the specific "profile" for which they were developed to attack.
In 1997 and 1998, the first two monoclonal antibodies for the treatment of cancer were launched: Rituxan for the treatment of relapsed indolent non-Hodgkin's lymphoma, and then Herceptin for the treatment of breast cancers which had an abundance ("overexpression") of a protein called HER2 on their cell surface.
And these were only the first two of what are expected to be hundreds of highly specific monoclonal antibody therapies being brought to market in the coming decade. In 1998, therapeutic monoclonal antibody revenues for the seven major pharmaceutical markets (U.S., France, Germany, Italy, Spain, the United Kingdom, and Japan) were approximately $499 million. By 2008, they are expected to grow to $4.4 billion.
The major areas of current research into treating cancers with monoclonal antibodies include breast cancer, ovarian cancer, non-small-cell and small-cell lung cancers, prostate cancer, the acute leukemias, non-Hodgkin's lymphoma, and colorectal cancer.
Monoclonal Antibodies
Antibodies are proteins made by the body's own natural immune system that are directed against foreign and infectious agents called antigens. Monoclonal antibodies are engineered through biotechnology to imitate immune system antibodies by providing specific actions against cancer cells.
Herceptin is a monoclonal antibody that attaches itself to HER2 protein receptors on the surface of cancer cells. When there is an overexpression or abundance of these receptors, it is easier for Herceptin to find targets. By binding to the HER2 proteins on the surface of these cancer cells, Herceptin is able to slow their growth and reduce the spread of tumors.
This overexpression of the HER2 protein occurs in 25 - 30 percent of breast cancer patients and may result in a more aggressive form of the disease. Also, the disease may not be as responsive to standard therapies, including certain regimens of chemotherapy.
New Twist for the FDA
The Food and Drug Administration recently took the highly unusual step of publicly supporting a product-Herceptin-in the face of a barrage of negative press.
While Herceptin has been used to treat more than 25,000 women since it was first approved by the FDA in late 1998, the drug's manufacturer, Genentech, recently issued a warning that 62 patients have had serious problems with the drug. Fifteen patients eventually died.
All of the patients experienced allergic reactions to the drug after the initial dose, and some of the deaths may have been the result of other complications from their cancers. However, both Genentech and the FDA agree that Herceptin is one of the "least toxic" of the breast cancer drugs currently on the market, as well as one of the most promising.
The FDA publicly backed the continued use of Herceptin after the manufacturer's warning because it noted that such reactions to the drug are "rare" and occur at similar levels with other cancer drugs. Furthermore, the drug's promising results in breast cancer studies cannot be ignored. In one clinical trial, patients who had both chemotherapy and Herceptin demonstrated a 25 percent increase in survival compared with those taking chemotherapy alone.
In the News
At the recent Department of Defense Breast Cancer Research Program meeting in Atlanta, Dr. Michael DiGiovanna of the Yale University School of Medicine presented the results of a study that found that the HER2 protein receptors on cancer cells may be in either an "active" or a "passive" state.
DiGiovanna said his research found that the majority of tumors demonstrating an overexpression of the HER2 protein might actually have the protein in a less aggressive resting or passive state. In fact, he found that only 12 percent of the tumors with the overexpression of HER2 had the protein in the more aggressive active state.
The use of Herceptin, particularly when used in conjunction with other anticancer drugs, can have some significant side effects, including a risk of heart muscle damage. Therefore, DiGiovanna said, his findings could help doctors determine which patients might benefit more from Herceptin (those with "active" HER2 proteins) and which patients would be better served by other treatments for their disease.
Testing for HER2
Testing for overexpression of the HER2 protein is done on tumor tissue and should ideally be performed at the time of diagnosis. Patients who want their HER2 status checked should ask their physician to have testing done at the time of biopsy or surgery, or on their stored tumor tissue.
Pathology labs often keep biopsy tissue for a number of years, so your tissue can potentially be evaluated for HER2 protein overexpression well after your initial diagnosis. Your doctor can request that the HER2 test be performed on the stored tissue sample, commonly called "archived tissue."
If you are told that your tissue is no longer being stored, you may want to consider requesting a new biopsy. Fortunately, newer, less invasive methods of taking breast tissue samples are now available, including fine-needle aspiration and core biopsy.
Once your tissue is obtained, either from a new biopsy or from archived tissue, the HER2 test is performed by staining the tissue with a specific solution, or reagent. The test is then evaluated by a pathologist, who looks for highlighted areas where high levels of overexpression are present. Depending on the level of staining, your tissue sample may be classified as HER2 positive, which means that you may be a candidate for Herceptin monoclonal antibody therapy.
SOURCES:
The U.S. Food and Drug Administration (www.fda.gov)
Department of Defense Breast Cancer Research Program meeting, June 9, 2000, Atlanta, GA
Genentech Corporation (www.herceptin.com)
"Therapeutic and Diagnostic Monoclonal Antibodies for Cancer," Decision Resources, Inc.
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