Posted on November 19, 2001 at 10:50 a.m.

BIRMINGHAM, AL — Antisense therapy shows promise in attacking two types of breast cancer and can enhance the effects of standard chemotherapy, according to a study from UAB (University of Alabama at Birmingham) and Hybridon, Inc., of Cambridge, Mass. Their work was published in the November issue of Clinical Cancer Research, a scientific journal.

Antisense therapy is a relatively new way of attacking cancer cells. The antisense approach involves a specific drug that inhibits the expression of a cancer-causing gene known as MDM2. The MDM2 gene is over-expressed in several human cancers, including breast, lung and colon cancer. MDM2 wreaks its havoc by affecting the work of another gene, p53, which exists to regulate the growth of cells. Tumors are caused by the unregulated growth of cells. Antisense therapy controls the production of MDM2, allowing the p53 gene to slow or stop the growth of tumor cells.

The finding is of particular significance because it demonstrates that antisense works against two types of tumors that contain a "wild" type or a mutant form of p53. Approximately half of all human cancers involve a "wild" type p53 gene. Other tumors express a mutated strain of p53.

"Antisense is of particular value because you don't have to worry about p53 status, so it can potentially be used for all types of tumors," says Dr. Ruiwen Zhang, associate professor of pharmacology and toxicology at UAB and a senior author of the paper. Zhang also is a senior scientist at UAB's Comprehensive Cancer Center.

The study also showed that antisense therapy enhances the effect of standard chemotherapeutic agents. "Antisense seems to sensitize cells to cancer therapy," Zhang says. In current chemotherapy regimens, it is common to combine several agents to maximize their effect. Use of antisense therapy with one chemotherapy agent could yield better therapeutic results. "This is of most value for patients who are resistant to standard chemotherapy agents. By using antisense therapy to sensitize the cancer cells, it is possible to treat a patient longer or use a lower dose."

Study authors Dr. Hui Wang and Li Nan are from UAB’s pharmacology and toxicology department. Co-authors include Dong Yu and Dr. Sudhir Agrawal of Hybridon. Agrawal also is president and chief scientific officer of Hybridon.

The work was supported by funds from Hybridon and from the National Institutes of Health.