Using precise, radioactively labeled genetic probes, researchers study cancer gene activity from outside the body

Using precise, radioactively labeled genetic probes, researchers at Jefferson Medical College have seen cancer gene activity from outside the body in laboratory mice. The probes, which work by attaching to genetic codes copied from an active cancer gene, may someday aid physicians and scientists in cancer detection and in determining the appropriate treatment for a cancer.

"Patients might be able to avoid a great deal of worry and unneeded surgery if cancer gene activity could be detected from outside the body," says Eric Wickstrom, Ph.D., professor of biochemistry and molecular pharmacology and microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and at Jefferson's Kimmel Cancer Center.

The scientists would like to detect cancerous breast tumors as early as possible, particularly before they begin to spread to other areas of the body. "We want to detect them before mammograms can find them," Dr. Wickstrom says. "We want to see whether a cancer gene is active, which will tell clinicians the best way to treat it, according to the cancer gene activity of the tumor. If we can see the hotspot of cancer gene activity before the tumor has formed, we can start to treat earlier." The researchers report their results in December in the Journal of Nuclear Medicine.

The gene, called cyclin D1, is turned on in the majority of breast cancers, he explains. The genetic probe, which is a DNA derivative, carries an attached radioactive label, and binds to cyclin D1 messenger RNA (mRNA). The latter is involved in translating DNA instructions and making proteins.

Dr. Wickstrom, Mathew Thakur, Ph.D., professor of radiology at Jefferson Medical College and their co-workers contend that the strategy – using genetic probes to visualize sites of cancer gene activity – can work for detecting the activity of other cancer genes in various types of tumors.

"The radioactive probes can help us identify the cancer cells at an early stage," says Dr. Thakur. "In this technology, we've shown the proof of principle. Several other cancers show characteristic activated genes that we might also be able to use for early diagnosis, such as pancreatic cancer, prostate cancer and colon cancer."

In 2004, approximately 40,000 women in this country will die from breast cancer. According to Dr. Wickstrom, clinical examination and mammography miss almost half of the breast cancers in women under 40, approximately one quarter of cancers in women ages 40 to 49 and one-fifth of cancers in women over age 50.

He notes that when suspect lumps are discovered, biopsies are necessary to tell if cancer exists or not. But when such lumps are removed after suspicious mammograms, two-thirds are found to be benign.

Dr. Wickstrom foresees this particular test for cyclin D1 – which he has used to detect estrogen receptor-positive breast cancers in mice – eventually being used in medical imaging centers. In addition to a mammogram, a woman could be tested with a genetic probe – another way, he says, to screen suspicious lumps. It could also be used to detect precancerous zones, as in ductal carcinoma in situ, and the spread and recurrence of cancer.

The researchers hope to conduct a clinical trial of their probes in suspected cases of breast cancer, and eventually, in other cancers as well. They are publishing their results testing for another cancer gene called MYC next month, and are studying other known cancer genes, such as K-RAS in pancreatic cancer.