Pancreatic cancer kills more than 40,000 people every year, and among cancers it’s particularly insidious. For 80 percent of patients, the disease is already so advanced at the time of diagnosis that treatment is unlikely to provide significantly life-extending benefits. For patients diagnosed with localized pancreatic cancer, the five-year survival rate remains barely above 20 percent, according to the National Cancer Institute. New research from scientists at Fox Chase Cancer Center in Philadelphia, which will be presented at the AACR Annual Meeting 2012 on Sunday, April 1, shows that a protein called survivin could be a useful tool in understanding pancreatic cancer - particularly for identifying which subsets of patients will most likely respond to treatment.
In a recent study of pancreatic cancer patients who had undergone tumor resection, the scientists found that patients who underwent different treatment regimens, following surgery, had different levels of survivin and experienced different lengths of disease-free survival.
“Biomarkers for pancreatic cancer are especially useful because the survival is so poor and it’s such a bad disease for people to get,” says Saad Khan, M.D., a medical oncology fellow at Fox Chase. “We’re looking for biomarkers that tell us how the cancer will behave, whether or not it’s a more aggressive type that will spread to different parts of the body. Most importantly for our research, we want to see if there are drugs that work better in patients with survivin than in those who don’t have it.”
They first studied cancerous tissues from 88 patients who had had pancreatic tumors, as well as nearby lymph nodes, surgically removed at Fox Chase. The researchers found higher levels of survivin in the cells from the lymph nodes than in the cells from the primary tumor. They went on to measure survivin in cells from 60 patients, of the original 88, who had undergone chemotherapy or radiation after surgery. The patients with higher levels of survivin lived longer periods of time before the cancer returned. The connection was strongest and statistically significant in patients who received the chemotherapy drug gemcitabine, though the researchers found similarly suggestive trends among patients who received radiation therapy or 5-FU.
“We found that when there was a higher amount of survivin expressed in the nucleus, there was significantly longer disease-free survival for all patients,” says Khan. “In terms of overall survival, patients treated with chemotherapy or radiation did better when they had higher amounts of survivin which goes against what we’d expected, but this did not achieve statistical significance. Our results suggest that people with higher levels of survivin responded better to specific chemotherapies.”
New Biomarkers for Prostate and Pancreatic Cancers and for Mesothelioma
Validated biomarkers hold promise for a more personalized and targeted approach to cancer therapy, and for improving diagnosis. In 2 preliminary reports, researchers say that they have potentially identified new sets of biomarkers that could be useful for prostate and pancreatic cancers and for mesothelioma.
The prostate cancer study identified a set of biomarkers that distinguish prostate cancer from benign prostate disease and healthy tissue with 90% accuracy, say researchers. Although the results are preliminary, they are very encouraging, according to John Anson, PhD, vice president of biomarker discovery at Oxford Gene Technology, in the United Kingdom, the company that is developing the technology.
In the second study, researchers identified biomarkers that appear to be specific to pancreatic cancer and malignant pleural mesothelioma. These biomarkers, developed by SomaLogic, were identified with novel aptamer-based proteomics array technology.
Both studies were presented at the 4th American Association for Cancer Research International Conference on Molecular Diagnostics in Cancer Therapeutic Development in Denver, Colorado.
Survivin - which is readily detectable in cancerous and embryonic tissues but not in most healthy tissue - is a protein that blocks apoptosis, or cell death. Because of its strong association with cancer, researchers have long sought ways to use survivin to better understand and treat the disease.
“Survivin has been looked at quite carefully in many cancers,” Khan says, “but there’s been no clear information about how it is expressed in a large number of pancreatic cells.”
Pancreatic Cancer Biomarkers Found
Five proteins linked to early development of pancreatic cancer have been identified by U.S. researchers, who said the finding is a step forward in efforts to develop a blood test to detect this type of cancer in the early stages, when cure rates are highest.
“Our team identified, for the first time, protein changes associated with early-stage pancreatic tumor development in genetically engineered mice that were also found to be associated with the presence of disease in humans at an early, pre-symptomatic stage,” senior author Dr. Samir Hanash, of the Fred Hutchinson Cancer Research Center in Seattle, said in a prepared statement.
They first identified the five proteins in mice with a precancerous condition called pancreatic intraepithelial neoplasma. The condition, if left untreated, eventually progresses to full-blown pancreatic cancer. The researchers then looked for the same proteins in blood samples from 13 people with asymptomatic, early-stage pancreatic cancer.
The study was published in this week’s issue of the online journalPLoS Medicine.
Khan, finishing up his third year of medical oncology training, came up with the idea to study survivin with his mentor, Barbara A. Burtness, M.D., associate director for clinical research and professor of medical oncology at Fox Chase. The researchers used a surgical specimens linked to a patient database prepared by coauthor and surgical oncologist John P. Hoffmann, M.D.