Pancreatic cancer, a highly lethal malignancy, is the fourth most common cause of cancer-related mortality in the United States. Approximately 25 percent of patients with early cancers undergo potential curative treatment with surgery and chemotherapy. Unfortunately, only about 30 percent of patients who receive this intervention experience long-term cure. Part of this high mortality rate is attributed to a lack of effective diagnostic and prognostic tests. Researchers at Moffitt Cancer Center have utilized modern advanced technology and developed a prognostic test that can determine which early-stage pancreatic cancer patients will have a better outcome following surgery.
"There is an unmet need to develop a reliable test which will better predict prognosis for patients with early pancreatic cancer and thereby allow for personalized treatment and the wise investigation of novel interventions. New strategies, such as our discovery of a gene signature that can discriminate between patients, hold the promise that in the future patients who will not benefit from surgery can be identified and offered other treatments that may be more beneficial to them," said first author Dung-Tsa Chen, Ph.D., senior member of the Biostatistics and Bioinformatics Department at Moffitt.
"At the moment, we are forced to offer this aggressive treatment to all patients because we cannot tell who should be spared the trauma and inconvenience of the surgery when they will not benefit from it," explained senior author Mokenge Malafa, M.D, F.A.C.S., department chair and program leader for Moffitt's Gastrointestinal Oncology Program. "This could lead to patients being either under-treated or over-treated."
Moffitt researchers wanted to devise a genetic test that could function as a prognostic indicator of which patients with early stage pancreatic cancer are more likely to have better outcomes. They analyzed the genetic signature of 63 patients who had surgery for early stage pancreatic cancer and discovered that low expression of a set of 15 genes was associated with longer survival while high expression was associated with shorter survival. The researchers validated that the 15-gene signature could predict survival by testing it in an independent study with 102 early-stage pancreatic cancer patients and also translated the signature from microarray platform to NanoString platform for future clinical use.
The researchers hope that in the future, patients will be tested for the presence or absence of this 15-gene signature and placed into a surgery/chemotherapy treatment plan only if they will benefit from it. All other patients could be assigned a different treatment plan that could offer a better outcome and longer survival.
The development of this genetic test was made possible by patients who participated in Moffitt's Total Cancer Care® Program and donated tissue samples to advance scientific research in pancreatic cancer. The study was published Aug. 6 in the online journal PLoS One and was supported by grants from the National Institutes of Health (5P30CA076292 and 1R01CA129227) and from funds the DeBartolo Family Personalized Medicine Institute Pilot Research Awards in Personalized Medicine.