DALLAS - October 28, 1998 - Researchers at UT Southwestern Medical Center at Dallas are using the p53 gene, inserted into an inactive common-cold virus, as a novel way to attack ovarian cancer in a patient.
Drs. Carolyn Muller and Robert Coleman, assistant professors of obstetrics and gynecology, said p53 is known as the housekeeper gene because it patrols for damaged cells, and if the cells cannot be repaired or are growing out of control and can't be contained, the p53 gene turns on its second line of defense: a built-in cell-death program, a process called apoptosis. The p53 mutations are the most common mutations in solid tumors and are found in 50 percent to 79 percent of ovarian cancers.
Muller said the normal p53 genes are replicated in the laboratory and inserted into adenoviruses, which act as carriers. During the treatment procedure, the patient's large amount of abdominal fluids, caused by the cancer, is withdrawn, and a therapeutic mixture of engineered p53 genes floating in saline is injected into the abdominal cavity. There the viral "geneboats" deliver the p53 gene to all cells. Once the gene is turned on in cancer cells, the invading "housekeeper" goes to work, recognizes the cancer cell's DNA damage and condemns it to death.
Muller and Coleman, who work in the Harold C. Simmons Comprehensive Cancer Center and the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research, said that this trial will determine several things. They include the appropriate mixture of engineered viruses in the solution, the sequence of doses, the length of treatment and the manner in which the patient reacts to it. The first patient's treatments are occurring in three weekly visits with two-week intervals between them. Patients will continue treatments as long as a positive response occurs unless significant side effects develop. Fifteen to 18 patients are expected to be treated in this study.