Researchers at the University of North Carolina in Chapel Hill have designed an implant that precisely supplies chemotherapy drugs to hard-to-reach pancreatic tumors using an electric field.
The approach, which Joseph DeSimone described during a presentation at the Koch Cancer Institute’s summer symposium in Cambridge, MA, on June 11, involves implanting an electrode carrying a reservoir of the drugs directly into the pancreas. When a second electrode is pinned to the side of the body or implanted inside, an electric field can be generated, driving the drugs out of the reservoir and into the tumor. Tests on pancreatic tumors in mice showed promising results that the team hopes to publish in the coming months.
Tumors in the pancreas sprout from the inner ducts of the tubular organ and spread quickly, sometimes gripping nearby arteries in a viselike stranglehold. Because they are pressed up close to delicate organs and vital arteries, these tumors are difficult to remove surgically. Treatment currently available to patients with advanced-stage pancreatic cancer is a customized combination of chemotherapy and radiation therapy. “Frankly [current treatment is] not very effective,” says Joel Tepper, a radiation oncologist at the Lineberger Comprehensive Cancer Center. “It does improve the median survival of patients by a number of months, but it’s not producing nearly the kind of dramatic effects we’d like to see.”
One reason that pancreatic tumors are so difficult to treat is that their poor blood supply limits the access of bloodborne chemotherapies to the cancerous tissue. Dosage concentrations are capped to prevent the chemotherapy from affecting healthy tissue as it courses through the rest of the body. “What you do is dose people up to the maximum toxicity level… you’re poisoning the whole body,” says DeSimone. “You’re trying to get something locally, and it’s just not getting there.”
Using the implant, the team has been able to send the drugs directly into the mouse tumor. “We now know that the drug is in these tumors in huge concentrations,” says DeSimone. The device also localized the chemotherapy to the area around the tumor. When blood from other parts of the mouse was tested for the drug, concentrations were below detectable limits. “For the focal delivery of the drug, this is a huge opportunity,” DeSimone says. “But we need more time to verify that we can actually prove the outcome, by shrinking the tumors.”
A potential application of this device will be to shrink large, inoperable tumors, pulling them away from vital organs and enabling surgeons to access them. “Only one in five patients who have pancreatic cancer will undergo surgery,” says Jen Jen Yeh, a clinical oncologist at the Lineberger Center and collaborator on the project. “If we increase the number of patients who are eligible for surgery, we may increase the number of people who have a chance of cure,” says Yeh.
The team has yet to show that the tumors shrink once the drugs have reached the tumors in mice. Also, since human tumors would need bigger electrodes, the lab has scaled up the implant and is testing it in dogs. Though the dogs lack tumors, the team can account for corrections in the amount of current delivered and the current density, which would differ for a larger electrode that could be used to treat human tumors.
“We hope to get this to the clinic in the next two years,” says James Byrne, an MD-PhD student in DeSimone’s lab who designed the electrodes. “We’re ensuring that the device is safe enough and efficacious enough that it can be used in patients.”