UF researchers receive $1 million grant to study colorectal cancer
University of Florida Shands Cancer Center researchers have received $1 million in federal funds to study a new molecular marker for colorectal cancer through a multicenter international trial. Each year, about 150,000 Americans are diagnosed with colorectal cancer. Of those patients whose cancer spreads, only about 5 percent survive five years because current tests to determine whether the disease is progressing aren’t always accurate.
Physicians typically measure the levels of chorioembryonic antigen, or CEA, that tumors release into the bloodstream to assess whether the disease has migrated out of the intestinal tract. But other tumors also generate CEA, so it is not a specific indicator of colorectal cancer.
Pathologists also examine a sampling of patients’ lymph nodes to see whether tumor cells are present, but accuracy is a problem because it’s impossible to check every part of every node.
UF researchers seek to confirm that a compound called guanylyl cyclase C, or GCC, is a more precise marker for colorectal malignancies. Preliminary studies have shown it has promise, particularly in signaling that cancer has metastasized, said Dr. Scott Schell, an assistant professor of surgery and of molecular genetics and microbiology at UF's College of Medicine and the UF Shands Cancer Center. That’s likely because GCC is only produced by cells that line the intestines and by those that turn malignant and travel elsewhere in the body.
Schell is the study’s principal investigator at the UF site. Thomas Jefferson Research Hospital in Philadelphia is subcontracting the research to UF through a grant it received from the National Cancer Institute. McGill University in Montreal also is participating.
UF surgeons will examine GCC levels in tumors taken from 200 patients undergoing surgery for colorectal cancer. They also will remove lymph nodes that will be examined in the laboratory using a gene amplification technique. The approach will enable scientists to detect the genes that produce GCC if they are present in the lymph nodes, a sign that cancerous cells are no longer confined to the bowel.
“If a single copy of a gene is present, this method can replicate it millions of times in a short period of time, allowing us to use specific genetic probes to determine if the gene is present and how much of the gene is around,” Schell said. “The analogy goes beyond finding the ‘needle in the haystack’ to more like finding a ‘single grain of sand on the beach.’”
Scientists also will study whether GCC levels in tumors predict the degree of lymph node involvement, the need for chemotherapy, the likelihood of disease recurrence or spread, and the prognosis for survival, Schell said. Study participants will be tracked for five years.
“The end goal will be to determine whether we can recommend that the current pathology examination of lymph nodes can be more accurately, more quickly and more cheaply performed using this gene amplification technique after surgery for colon and rectal cancers,” Schell said. “Also, preliminary studies are under way to examine whether gene amplification can be performed on a simple blood test, for use in following patients with the diagnosis of colon and rectal cancers, and perhaps even as a future screening test.”
Work by Dr. Rodwige J. Desnoyers, formerly an assistant professor of medicine in the division of hematology/oncology at UF’s College of Medicine, helped lay the groundwork for the latest study. In recent years, Desnoyers, who collaborated with Thomas Jefferson scientist Dr. Scott Waldman, published findings from retrospective studies showing that measuring GCC levels caught cancer recurrence in colon cancer patients, even when standard tests missed it.
At UF, Schell is collaborating with Dr. James Crawford, a professor and chairman of the department of pathology, immunology and laboratory medicine; and medical oncologist Dr. Robert Marsh, an associate professor of medicine.