SALT LAKE CITY — Scientists at the Huntsman Cancer Institute made a recent discovery in cell research that could change the way pancreatic cancer is treated in the future.
By turning on a protein in mice in the early stages of the cancer, scientists were able to block the disease from spreading and even reverse its effects, said Charles Murtaugh, institute researcher and associate professor of human genetics at the University of Utah.
Murtaugh served as senior author on the research published recently in Developmental Cell.
In early stages of pancreatic cancer, researchers have been trying to understand how the disease begins and how the cells become malignant, he said. They wanted to learn what happens in “well-behaved” cells that produce digestive enzymes when someone develops pancreatic cancer.
“In pancreatic cancer those cells change and they become very proliferative, they become invasive, and they become tumor cells,” Murtaugh explained.
A few years ago, the researchers discovered a protein called PTF1A that helps pancreatic cells produce the digestive enzymes. “All the normal things that those cells do typically is regulated by this PTF1A,” he said.
But that protein disappears when someone has pancreatic cancer, according to Murtaugh, making the cells more prone to becoming cancerous.
Initially, the study was performed in mice in the early stages of cancer. The scientists watched the tumors begin to form. In a normal mouse, the tumors take “many, many months,” even a year to develop, until they look like human cancer. But when scientists took PTF1A out of the mice, it takes just weeks for them to develop “full-blown invasive tumors,” Murtaugh said.
Scientists then wanted to discover if the protein was prevented from going away, would it stop the tumors from forming?
In mice, keeping the protein turned on in the genetically modified mice “completely prevented” the tumors from forming. The cancerous cells would either die “or go back to being normal cells,” he said.
“So this is one of the first times that we know of where it’s been possible to take these pre-cancerous cells and revert them back to normal, even though they have all the genetic changes of cancer. That’s sort of the thing I like about our work,” Murtaugh said.
“I think what our work points to is that there are nongenetic factors that are also important (in cancer),” he explained. “That is, PTF1A ... is not mutated. It’s not that the DNA is damaged in pancreatic cancer. It’s just that the protein gets turned off.”
He thinks the treatment could be enough to prevent or reverse pancreatic cancer in its early stages. The findings could eventually be turned into a treatment for humans.
When the researchers submitted their study for publication, reviewers suggested they perform the experiment on human cells as well. Murtaugh said the team thought the human cells — which came from people with life-threatening tumors — would be “kind of too far gone” to respond to the protein.
But they found that about half of the human cancer cells in which the protein was restored stopped growing, he said.
Now, the researchers are trying to discover why.
They also hope to find a drug that will turn PTF1A on in humans. Within a year, they should be able to start screening for drugs, Murtaugh said.
“We might not find one, but if we did find one, then within five (to 10) years we might be at the point to beginning to think about clinical trials,” Murtaugh said.
Genomes in cancer patients can’t be manipulated in the same way as in the genetically-modified mice, but “the technology is always improving” and Murtaugh said he sees a time when it might be possible clinically.
The study shows that “the genetic changes that happen in cancer are not the ‘be all and end all’ of what makes a cell bad or good. And in some cases, people have been able to make drugs that go after, that really target the genetic changes that have happened in the cancer cell. ... But in pancreatic cancer, the genetic changes that happen are hard to target with drugs,” Murtaugh said.
The mutation that happens in pancreatic cancer currently is “not easily druggable,” he said.
The discovery could lead to treatments for other cancers that are also currently difficult to treat with drugs, according to Murtaugh.
“I think that approach probably has applicability beyond pancreatic cancer at well. Because of course, there are a lot of cancers for which we don’t have very good treatment. And I think in most of those cases, the genetic changes only work if there are other nongenetic changes as well.”