Guanylyl Cyclase C (GCC or GUCY2C) Marker for Colorectal Cancer
DiagnoCure owns the exclusive worldwide diagnostic rights to the Guanylyl Cyclase C (GCC or GUCY2C) marker and its applications to colorectal cancer. In September 2008, the Company launched its proprietary Previstage™ GCC, Colorectal Cancer Staging Test. Since July 2011, the test is offered by Signal Genetics. GCC is a gene coding for a protein found in cells, both normal and cancerous, lining the intestine from the duodenum to the rectum. It is involved in multiple functions, including water transport, crypt morphology and suppression of tumorigenesis. It is not normally found in tissue in other parts of the body. When GCC is detected outside of the intestine, it is an indication of the presence of colorectal cancer metastases.
Dr. Scott Waldman, at Thomas Jefferson University, first identified the relation between GCC and colorectal cancer in the early 1990s. GCC mRNA has shown to be highly accurate in detecting the spread and recurrence of colorectal cancer, respectively in lymph nodes and blood, thereby representing a significant improvement over traditional detection methods. To date, over 50 peer-reviewed journal articles have discussed the relationship between GCC mRNA and colorectal cancer (visit our Scientific Publications page for a listing). In particular, results of studies on the GCC mRNA, totaling over 1,000 patients, have been published. Below is a summary of the most recent ones:
Initial studies
The U.S. National Institutes of Health (NIH) provided two grants amounting to over $10 million to Dr.Waldman for two prospective five-year multicenter studies of the GCC marker as it relates to its potential clinical uses in colorectal cancer. The first study, on GCC testing of lymph nodes to better determine risk of recurrence, was completed and published in the peer-reviewed Journal of the American Medical Association (Feb.18, 2009, Vol.301, No.7). The study was performed with over 400 enrolled CRC patients from nine different sites. The results strongly demonstrated that testing of lymph nodes for GCC can more accurately predict the risk of stage I and II colorectal cancer (CRC) patients having disease recurrence.
In a group of 257 stage I and II CRC patients, when GCC was considered with other factors, patients whose nodes were GCC positive were 4.7 times more likely to develop disease recurrence than those whose nodes were GCC negative, and 3.3 times more likely to die within three years. In fact, patients with GCC positive nodes had a risk of recurrence and survival rate comparable to that of stage III CRC patients.
The second study sponsored by the NIH is evaluating whether detection of GCC in the blood can identify earlier recurrences of colorectal cancer.
GCC as a prognostic marker of disease recurrence
In January 2010, at the Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology (ASCO GI), DiagnoCure presented the results of a study on the GCC marker used in its PrevistageTMGCC test. The study analyzed the results of the GCC molecular test on lymph nodes of 123 patients that were considered having stage II cancer by standard pathology assessment. It demonstrated that patients who had at least one GCC positive lymph node were two times more likely to experience recurrence of their cancer than patients who had no GCC positive lymph nodes. The study was also published in the Journal of Clinical Pathology (2010, vol. 63, 530-577).
In 2010, DiagnoCure completed the first phase of a new clinical study, called VITAR (Validating Indicators To Associate Recurrence Risk) aimed at confirming that PrevistageTMGCC can more accurately predict the risk of recurrence in stage II colorectal cancer patients, who are considered low risk by traditional histological assessment methods. This study is headed by Daniel J. Sargent, Ph.D., Professor of Biostatistics and Oncology at the Mayo Clinic, as the Principal Investigator.
The first phase of the study included 241 stage II colorectal cancer patients, from six Canadian and American clinical sites. These patients had undergone surgery for colorectal cancer in the prior ten years, and all had at least three years of follow-up. None had received adjuvant chemotherapy. Yet, 12% of these patients had recurred with a more advanced cancer. The study demonstrated that PrevistageTMGCC could stratify these 241 patients into a high risk group and a low risk group. In particular, in a subset of 181 patients, with traditionally favourable prognostic factors T3 tumor and 12 or more lymph nodes examined, the PrevistageTMGCC test classified 1/3 of patients with a high risk of recurrence at five years following the surgery, and 2/3 of patients at low risk of recurrence. In this subset, the high risk group had a 6 times greater likelihood to recur than the low risk group (27% vs 4%). DiagnoCure intends to pursue the second phase of the study to further validate these positive initial results.
The study was presented at the 2011 Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology («ASCO GI») held in January in San Francisco, and published in May 2011 in the Annals of Surgical Oncology.