OU researchers study cancer that kills nine out of 10 who have it
Oklahoma City — Pancreatic cancer doesn't much care what you throw at it.
The disease kills about 92 percent of people who have it, including Apple CEO Steve Jobs, “Harry Potter” actor Alan Rickman and, less than a month ago, “Queen of Soul” Aretha Franklin.
The only good thing is that its one of the less-common cancers.
Survival rates have increased dramatically for most cancers since the 1970s. It's been much harder to make progress against pancreatic cancer, said Dr. Min Li, co-leader of the preclinical translational research program at Stephenson Cancer Center.
Survival “hasn't improved much over the last 20, 30 years,” he said.
Pancreatic tumors almost never cause symptoms in their early stages, so patients have no idea they're sick until the cancer has spread to the liver or other organs — when it's too late for surgery to be effective. There's no reliable test to detect it in people who don't have symptoms. To make matters worse, pancreatic cancer often becomes resistant to chemotherapy, and radiation doesn't work well either, Li said. So far, immunotherapy hasn't been shown to work for it.
Researchers at the OU Health Sciences Center are trying to figure out what makes pancreatic cancer so difficult to kill, or even slow down. If the ideas they are pursuing pan out, it could give future patients a better chance, though the odds of anything developing fast enough to help current patients are slim.
Dr. Priyabrata Mukherjee, associate director of translational research at Stephenson, said pancreatic cancer behaves differently from most other tumors. Typically, tumors have lots of blood vessels in them, bringing oxygen so the cancer can grow — and giving doctors a way to fight the tumor by sending chemotherapy through the bloodstream. Pancreatic cancer doesn't do that. Instead, its cells “escape” from the pancreas, where the oxygen supply is low, to other organs that are more hospitable, he said. It's a solid strategy, if you're a tumor, but it leaves the patient with few options for treatment.
“I tell my students, you think of yourself (as a tumor), and somebody is trying to kill you, and how are you going to survive?” he said.
No silver bullet
Most pancreatic cancer patients have a mutation in a gene called K-RAS, which allows cancer cells to “drink” large amounts of nutrients, so they have the fuel to grow out of control. Mukherjee's lab is studying a protein called UBAP2, which appears to turn the K-RAS gene off — at least in mice. They need to learn more about UBAP2 before trying to make a drug like it, though, he said.
“We need to figure out all the functions of this molecule before we can take it to the next level,” he said.
K-RAS isn't the only important target, though, Li said. Before a tumor can take off, other things must go wrong, though researchers still are trying to sort out what all of them are, he said.
“It takes more than one genetic mutation to lead to pancreatic cancer,” he said.
Li's lab is studying ZIP4, a “transporter” that allows cells to take up zinc. Normally, cells in the pancreas don't need much zinc, but cancer cells do because of their rapid growth, Li said. Unfortunately, it isn't possible to just knock out ZIP4, because other types of cells need zinc. If they can come up with a way to knock it out only in the cancer cells, however, they might stop the tumors from growing, he said.
It appears ZIP4 also is related to the rapid weight loss and muscle wasting seen in people with pancreatic cancer, Li said. If the transporter were in check, patients might be able to stay strong enough to tolerate aggressive treatment, he said.
Right now, they're only testing ways to manipulate ZIP4 in mice, though. If they find a drug that works in mice, it could move into clinical trials to determine whether it works in humans.
Mukherjee's lab also is testing other ideas, such as interfering with tumor cells' ability to communicate with noncancerous cells around them or using nanoparticles to neutralize proteins that are important in the spread of cancer.
Still other researchers are working on trying to detect pancreatic cancer earlier, when it would be easier (but still far from easy) to treat. About 34 percent of people who have a pancreatic tumor detected before it has spread live at least five years.
Dr. Yi-fan Xu, a Ph.D. candidate at OU Health Sciences Center, is studying whether it's possible to create a blood test to detect pancreatic cancer. All cells release something called exosomes, which communicate with other cells or carry things between them. The goal is to figure out which kinds of exosomes are coming from pancreatic cancer cells, so they can find the cancer before it spreads.
Two types of exosomes that turn genes on and off seem like they could be important, Xu said, but the only way to find out for sure is to test more people. The initial study only examined blood from 15 people with early-stage pancreatic cancer. They need more patients to be sure that the same exosomes show up in a broad group of patients, and then need to compare the results to people who aren't sick, so they can figure out how much of those exosomes represents a problem. Even if it works, patients would still need more testing to be sure that they actually have cancer.
“If we find cancer at an earlier stage, the survival is much better,” he said. “They really need something to give them a hint.”