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Using survivin antibodies to detect cancer

Survivin has been established in the medical literature for a number of years as being one of the genes that is almost exclusively expressed in a number of cancers, but not in normal tissues. When thinking of developing a test to detect cancer or a therapy to treat cancer, you would want to focus on a substance that exists only with cancer cells. So it makes sense to use survivin, particularly with bladder cancer.

Survivin is excreted in the urine, allowing it to be collected and checked easily. Testing for a specific substance mirrors a broader trend in cancer detection and treatment toward using more specific rather than generalized treatments. The goal is to strike at cancer cells while preserving healthy tissues.

Lack of reliable screening test
There is a great need for a reliable, safe and easy test for bladder cancer. Bladder cancer is now the fourth most common cancer in the U.S., with about 53,000 cases diagnosed each year. Add in the fact that about 80 percent of cases of bladder cancer recur and you begin to realize the tremendous need for an accurate and simple test. At present, the best way to accurately diagnose bladder cancer remains performing cystoscopy and/or biopsy. These are invasive and sometimes painful tests and have to be frequently repeated to check for recurrence.

Testing for cancer
Using survivin from urine as the basis of a potential bladder cancer screening test made sense to us early on. Only when cancer is present will survivin be produced and be detected in the urine. Although our results from the JAMA study were initially very encouraging, at that time we felt we were a long way off from developing a screening test using survivin. But in the past year, Yale has entered into an agreement with a diagnostic company to develop such a screening test.

I would think a clinical trial of such a test could start in a relatively short amount of time. The biology is relatively simple and the assay used for the test is straightforward, sensitive and specific to cancer, meaning it could detect 100 percent of the cancers. Of course, before that could happen, it would have to be tested in a large, multicenter trial with hundreds of patients.

Low false positive rate
A good test should have a low false positive rate, that is, showing a positive result when no cancer is present. Our rate was 5 percent, considerably superior to urine cytology. Three of the patients in our study had hemoturia, blood in the urine, which is a symptom for bladder cancer. In most cases, the presence of blood does not automatically mean cancer but patients must still undergo additional testing to rule out cancer. Two of these patients in our study tested positive for survivin and later went on to develop bladder cancer so the changes we were detecting were very early changes.

How survivin works
Survivin may be protecting cancer cells from cellular suicide and making tumor cells resistant to such forms of treatment as chemotherapy or radiation therapy. While survivin is easy to detect in bladder cancer because it is excreted in urine, detecting it in other types of cancer is more difficult. In these cases, then, we would instead search for an antibody to the survivin protein.

The body naturally forms antibodies as a form of protection to foreign substances. Detecting these antibodies would be much easier than detecting the survivin itself and this is the basis of the research reported in this study.

Ideally, a test could be developed that would be used in the doctor's office and would be easy and give results quickly.

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Dr. Dario Altieri is a cancer researcher at the Boyer Center for Molecular Medicine and a professor of pathology at the Yale University School of Medicine.

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