Why is it so important to have a sensitive test for lung cancer?
Dr. Doyle: Lung cancer is the number one cancer killer of Americans, both male and female. It kills more people in this country than breast cancer, colon cancer, cervical cancer and prostate cancer combined. I found out that there was the possibility of developing a new blood test for lung cancer. The problem with lung cancer is that it presents at an advanced clinical stage. Most of the time it has at least spread to the lymph nodes before the patient has any clue that the cancer has developed. In the past, people have looked with chest X-rays and sputum analysis to see whether they could pick up lung cancers early, and that has not worked. Again the problem with a CAT scan is it's a separate radiographic procedure. What we have here at the University of Maryland is a blood test for lung cancer with the enzyme telomerase.
What happens when your cells divide and the DNA replicates?
Dr. Doyle: Each cell loses a little bit of DNA at the end of the chromosome with each replication, like a shoestring that has a little plastic tip at either end. The little plastic tips at the end of the shoestring are the telomeres. As the cells divide, you lose a little bit of the plastic tip with each division and eventually you get into unraveling the shoestring itself, and you lose valuable genetic material. The telomeres are important parts of the chromosome. Most normal cells don't have any way to protect this loss of material at the end of their chromosomes. That's why our cells get old and die. Cancer cells have learned the trick of turning on an enzyme called telomerase, which adds DNA to the end of the chromosomes and keeps this chewing down of the chromosomes from occurring.
Is this how cancer cells become immortalized?
Dr. Doyle: They can grow from one initial cell to billions of cells when the patient presents with a tumor. The interesting thing about telomeres is they are so widespread in cancer cells. In biopsies of cancer cells, different cancer cells -- up to 90 percent -- may have immortalization of the cells from activation of this telomeres enzyme. It's critically important to the survival and the growth of cancer cells. People have known to measure this enzyme in the tissue of cancer cells and have thought it was possible to measure this enzyme in the blood of patients with cancer. So a very sensitive assay was developed to pick up telomerase in the blood of lung cancer patients.
How successful has the test been in detecting cancer?
Dr. Doyle: We have looked at 65 patients with blood tests at the time of diagnosis. After initial radiation, chemotherapy and surgery, the patient gets a CAT scan to see how well the cancer is responding. When the patient is in remission, we get a telomerase reading every few months to see whether he's staying in remission. About 70 to 80 percent of patients with lung cancer have elevations of telomerase in their blood as opposed to almost zero normal control. Telomerase can use the reading to see patients go into remission with anticancer therapy. We can see it creeping up, but unfortunately the patient is going to relapse. We find it sometimes six months or more prior to the tumor coming back by a sensitive CAT scan.
Will you be able to detect other types of cancer early with this procedure?
Dr. Doyle: We have a long way to go with this assay to make it easily standardized and used in many hospitals, but if we are able to do this, then we may have a test for more cancers. At this point we know that we can pick up responses and relapses in lung cancer. As cancer therapy goes in to the area of biologic therapies, which are less toxic than standard chemotherapy, it may be very important to pick up these early relapses. We can give those patients nontoxic biologic therapies and then monitor their response even though there's no radiographic evidence of recurrence.
What is the future of the test?
Dr. Doyle: My initial reaction was that I wanted to be part of this project because this is such an important thing to be able to follow the course of the disease and pick up the disease early. Now lung cancer is the quintessential preventable disease. The next best thing is to be able to prevent people from smoking, and pick up the disease early. Our hope is to have telomerase turn out to be a prognostic feature where we can tell how a patient is going to do or respond to telomerase levels. We can monitor the people and treat them with less toxic therapy while following telomerase in the blood.