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Research at Mass General
A team of researchers from the Mass General Cancer Center and MIT have developed an innovative new strategy for treating pancreatic cancer with an implantable mesh patch designed to deliver chemotherapy drugs directly to the cancer site.
This flexible plastic disc is designed to treat pancreatic cancer at the source (Photo courtesy of Bryce Vickmark)
Let’s say there is a nail sticking out of the wall in your living room that you want to put back into place. Here are two ways you could go about it.
You could grab a hammer, walk into the living room, and gently tap the nail into the wall. Or you could swing a wrecking ball through the front of your house and hope it hits the nail with just enough contact to put it back into place without causing too much collateral damage.
The choice seems obvious, right?
In a way, though, the wrecking ball method has been the only option thus far for treating pancreatic cancer—soon to be the second leading cause of cancer death in the United States.
Researchers from the Mass General Cancer Center and the Massachusetts Institute of Technology (MIT) are hoping to change this by introducing a new strategy for treating pancreatic cancer that works more like the hammer than the wrecking ball.
In a recent interview, Matteo Ligorio, MD, PhD, explained the difficulties that are inherent in the current strategies for treating pancreatic cancer, and how the approach developed by the research team could help.
A big challenge in treating pancreatic cancer comes from its location in the body, Ligorio explained. The pancreas is buried between the stomach and spine, and surrounded by tissue, organs and nerves. This makes pancreatic tumors both painful and difficult to remove by surgery, especially if they have spread into surrounding tissues.
In many cases, the only method of treatment available is to dose the entire body with chemotherapy drugs administered through an intravenous line (IV). This approach has been met with limited success.
Chemotherapy drugs can be effective if they reach their target, but it is a big “if,” Ligorio said. The drugs have to travel a long way through the body to reach the pancreas, increasing the chances that they are diluted or diverted along the way. If and when they do reach the target site, it can be difficult to penetrate the tumors due to their tough outer membranes and lack of blood vessels, which limits the access points for the drug.
Plus, like a wrecking ball, the drugs can cause a lot of collateral damage to healthy cells on their way in and out of the body.
These treatment obstacles contribute to the disease’s high mortality rate. If it is not possible to shrink the size of a pancreatic tumor to the size where surgical removal is possible, the prognosis for patients is grim. Only 8% of pancreatic cancer patients will survive for longer than five years without surgery, Ligorio noted.
Despite the difficulties inherent in this approach, much of the funding and effort in pancreatic cancer research has gone into finding new, more powerful chemotherapy drugs. In a sense, the focus has been on building a bigger wrecking ball.
The team’s innovative new treatment strategy, which was developed by a multi-disciplinary team led by David Ting, MD and Jeff Clark, MD, of the Mass General Cancer Center and Elazer Edelman, MD, PhD, and Robert Langer, ScD of MIT, seeks to shift the starting point of chemotherapy treatment to the tumor itself.
To accomplish this, the team created a small, thin biodegradable polymer disc that can be infused with chemotherapy drugs and rolled up inside a catheter. Using non-invasive laparoscopic surgery, the disc could be inserted into the body via the catheter and placed directly on the tumor itself. The flexible design would enable surgeons to conform the disc to the shape of the tumor.
The disc is designed to act as both a physical and chemical barrier. From a physical standpoint, it functions as a makeshift “cage” that helps to limit the spread of the tumor. From a chemical standpoint, it is designed to administer a steady, slow dose of chemotherapy drugs directly at the point of need, while limiting damage to surrounding organs and tissues.
In a study of laboratory models of pancreatic cancer, the researchers found this approach was 12 times more effective in reducing tumor size than traditional IV drug treatment. The team is now gathering data to support a clinical trial in human patients, and has worked with the Partners Innovation office to create a company, PanTher Therapeutics, to bring the treatment to market.
If their disc-based strategy proves effective in treating pancreatic cancer in humans, there may be an opportunity to test it in other types of cancer as well, says Laura Indolfi, PhD. Indolfi worked on the project as a postdoctoral fellow at Mass General and MIT and is now the CEO of PanTher Therapeutics.
“By rethinking the way we deliver the drug, we not only make it more powerful and less toxic, we are also opening the door to finding innovative new solutions for other problems in pancreatic cancer patients and beyond.”
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