Most pancreatic cancer patients die soon after diagnosis, but researchers have identified an oncogene that appears to be a promising new treatment target.
Even more hopeful is that drugs that target this oncogene are already approved to treat rheumatoid arthritis and are undergoing tests with colon and lung cancers, said lead researcher Nicole Murray, an assistant professor of pharmacology and senior associate consultant in the department of cancer basic science at the Mayo Clinic’s Jacksonville, Fla., branch.
“Pancreatic cancer is a highly lethal disease,” Murray said. “The current chemotherapeutics that we have available have not been very effective.”
For the study, published in the March 1 issue of Cancer Research, Murray’s team looked at the role the oncogene PKC-iota (PKCi) plays in pancreatic cancer. This gene has already been implicated in colon and lung cancers.
The researchers have been studying another gene called KRAS, which is mutated in 90 percent of pancreatic cancers and controls PKCi, but KRAS has not been easy to target with drug therapy, Murray noted. This is why they decided to investigate PKCi.
They found high levels of PKCi, which predicted poor survival, in most of the pancreatic cancer tumors sampled. Patients with high PKCi levels survived an average of 492 days, compared with 681 days for patients with low levels of the oncogene.
Five-year survival was 10 percent for those with high PKCi levels, compared with 29.5 percent for patients with low PKCi levels, the researchers noted.
In addition, in experiments in both cells and animals, the researchers found that PKCi was essential for the growth of pancreatic cancer cells.
“When we knocked out the PKCi genes in pancreatic cancer cells, we showed that these cells did not grow as cancer cells very well; they didn’t invade other tissue very well,” Murray said.
“When we put these cells into mice, we showed that not only did the tumors not grow very well, but they didn’t metastasize well,” she said.
These findings suggest that the arthritis drug aurothiomalate (Myochrysine), which targets PKCi, could effectively treat pancreatic cancer alone or combined with other chemotherapy. It could prevent pancreatic cancer cells from growing or make other chemotherapy more effective, Murray said.
Aurothiomalate is already in a phase I clinical trial for lung cancer patients at Mayo’s Minnesota and Arizona sites, Murray said. A phase II trial being planned will combine aurothiomalate with drugs that target other molecules in these cancers, she noted.
It is possible that a future trial will test aurothiomalate in pancreatic cancer patients, she said.
Besides treating pancreatic cancer, PKCi might also be useful in diagnosing the disease, she added.
The findings intrigued William Phelps, program director for translational and preclinical cancer research at the American Cancer Society. “Pancreatic cancer is in dire need of new therapeutic opportunities. Those things we’ve got don’t seem to work well,” he said.
Each year, about 40,000 new cases of pancreatic cancer are diagnosed in the United States, and about 35,000 people die from it, Phelps said. “Typical survival after diagnosis is five to seven months,” he said.
Pancreatic cancer is particularly resistant to treatment, and most cases are diagnosed when the disease is advanced, said Phelps.
The current drug approved to treat it, gemcitabine (Gemzar), is only minimally effective, Phelps said. “It’s not really giving more than a two-month life extension,” he said.
Targeting PKCi could be worthwhile, Phelps said. “This looks like a pretty good idea to go forward,” he said.
Combining gemcitabine with a drug that targets PKCi could extend life expectancy, Phelps said.
Michelle Duff, director of research and scientific affairs at the Pancreatic Cancer Action Network, also finds these results encouraging.
“There is an urgent need for more effective treatment options in pancreatic cancer to improve patient outcomes,” she said. “We are eager to see the results of further studies in preclinical models and eventually clinical trials.”