University researchers isolate 'KILLER' gene targeting cancer

Mark GlassmanMark GlassmanThe Daily Pennsylvanian Cancer will kill over a half a million Americans this year, and over 1.3 million new cases are expected to be diagnosed in 1997, according to the American Cancer Society. The disease is the second leading cause of death in the U.S. The identification of the anti-cancer gene KILLER/DR5 could be a giant step toward advances in treating most forms of the disease. "These findings suggest that substitution or reactivation of KILLER/DR5 in cancer cells may be a reasonable strategy for killing those cells," said Medicine and Genetics Professor Wafik El-Deiry, the senior author of a report on the research appearing in the October issue of Nature Genetics. Chemotherapy and radiation are conventionally used to initiate the activity of the KILLER/DR5 gene, but the dangerous clinical treatments expose patients to high levels of toxicity which can occasionally lead to death. "I suspect there must be another way of turning this gene on," El-Deiry said. He added that if researchers "could find less toxic or more specific ways to activate this biochemical pathway," doctors might be able to cure patients of cancer without subjecting them to potentially lethal treatments. El-Deiry identified the gene by comparing the DNA of cells that were resistant to chemotherapy to those which were more sensitive to the treatment. He found there was an abundance of KILLER/DR5 in the sensitive cells. In studying the gene's structure, El-Deiry discovered that KILLER/DR5 has two main components: a surface receptor on the outside of each cell and a "critical segment" inside each one. Activating the receptor -- typically by way of another gene -- starts a chain reaction which ultimately leads to cell death. Having established the gene's structure, El-Deiry tested KILLER/DR5's usefulness by inserting extra copies of the gene into cancer cell culture. "It just wiped out [the cells'] growth," he said. "We'd get these plates, and they just basically had no cells on them." Having identified the gene's usefulness in fighting cancer, he said researchers must now find a better method of activating KILLER/DR5 in patients suffering from the disease. Although El-Deiry successfully localized the gene on the human genetic map, he said it will take researchers years to find KILLER/DR5's precise location because such research requires the development of cancer in live animals.