====================== JeffNEWS, June 1, 1995 ====================== Jefferson Researchers Find New Way to Diagnose Colorectal Cancer Earlier ------------------------------------------------------------------------ A discovery by Jefferson researchers offers hope of early detection of the spread of cancer from its origin in the intestine to other sites in the body. If proven successful, the discovery could save countless lives from colorectal cancer, the second leading cause of cancer death in the United States and the world. The discovery culminates two years of research conducted by a team led by Scott A. Waldman, MD, PhD, medical director of the Clinical Research Unit, division of clinical pharmacology and associate professor, departments of medicine and pharmacology. Dr. Waldman's team includes Stephen L. Carrithers, PhD, senior postdoctoral fellow, department of medicine. Key to the discovery is the finding by Dr. Waldman's team of a protein "marker" found only in cells lining the wall of the intestine. When these cells become cancerous, they travel through the bloodstream to other parts of the body. Detecting these migrating (metastatic) cells, by technology specifically developed to spot the marker protein at the molecular level, means metastatic colorectal cancer can be detected much earlier than previously possible, says Dr. Waldman. The fact that the cells could have come from only one place - the intestine - tells doctors that a patient's colorectal cancer has spread, explains Dr. Waldman. Surgery Much Less Effective When Cancer Spreads ----------------------------------------------- Traditionally, colorectal cancer is treated by surgery - removing parts of the affected colon. Too often, however, the cancer spreads from the colon to other parts of the body, with detection at the new site coming too late for surgery to be successful. "If the cancer is confined to the intestine, surgery is a very successful treatment," says Dr. Waldman. "However, in half the patients diagnosed with colorectal cancer, the disease has already spread to other parts of the body. Those patients have less than a 5 percent chance of being alive after five years. Unfortunately, those statistics have not changed in 40 years. "We hope that our discovery will lead to new ways to diagnose and treat this disease that will significantly improve those statistics," says Dr. Waldman. For their research, Dr. Waldman and his colleagues have screened about 200 tissue samples from patients at Jefferson who have cancer or other diseases. "So far, in every case," he says, "the molecular test looking for the marker protein has been correct. We have found the marker protein in every patient who has been confirmed to have colorectal cancer. In contrast, this protein marker was absent in those patients who don't have this disease." The technology making possible Dr. Waldman's research findings depends on the unique molecular recognition between the marker protein in colorectal cancer cells and a small peptide produced by bacteria-like E. coli. The bacterial peptide specifically binds to the protein marker in cancer cells, allowing doctors to detect the marker's presence. By further developing this technology, which is analogous to target-seeking missiles, doctors can track the path of cancer cells spreading in a patient's body. A longer range goal is to apply this same "targeting" technology to selectively deliver toxic molecular bombs to metastatic cancer cells without harming surrounding normal cells. Research to this end is now under way in Jefferson laboratories. Blood Test and Gene Therapy Future Research Goals ------------------------------------------------- Other research based on the same "targeting" technology is aimed at developing a blood test that would screen patients for undetected colorectal cancer or track patients for this disease following surgery, Dr. Waldman adds. Further on the horizon is the prospect of employing this technology for gene replacement therapy, where molecular missiles would specifically deliver payloads to correct the underlying genetic defects which cause malignant cells to be cancerous. Research related to the molecular "targeting" technology being pursued by Dr. Waldman's team is supported by grants from Targeted Diagnostics and Therapeutics, Inc., NIH, and the Elsa Pardee Foundation. Several patents concerning this technology and its diagnostic and therapeutic applications are pending in the U.S. Patent Office. Commercial aspects of this work are being handled by Jefferson's Office of Technology Transfer, directed by Abram Goldfinger. Working with Dr. Waldman on the research are two Jefferson surgeons, Pauline K. Park, MD, assistant professor of surgery and director of the University Surgical Service, and Scott D. Goldstein, MD, assistant professor of colorectal surgery. "In looking ahead, we hope that the unique protein markers and molecular recognition we are finding so promising for detecting and treating colorectal cancer are not limited only to that one cancer. Rather, we are hopeful that unique kinds of targeting molecules can be found for breast, lung and other types of cancers. If so, those will be truly exciting discoveries," Dr. Waldman concludes. ------------------------------------------------------------------------------ Information provided by: Editor, JeffNEWS (215) 955-6204 ------------------------------------------------------------------------------