Researchers at UMass Amherst have made significant advances in the treatment of pancreatic ductal adenocarcinoma (PDAC) with a new nanoparticle-based method. A new study details how nanoparticles are used to activate the immune response and target tumors, offering new insights into fighting this aggressive form of cancer.
A new hope for treating pancreatic cancer – Photo Archive
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, with a five-year survival rate of just 13%, and is the third leading cause of cancer death, according to a university release.
Researchers from the University of Massachusetts Amherst School of Medicine (UMass) have tested a new method of treatment for this type of cancer on mice. The study, published Wednesday in the journal Science Translational Medicine, highlights the synergistic effects of an innovative nanoparticle drug delivery system designed to activate immune pathways and target tumors.
A significant obstacle in treating pancreatic cancer is the microenvironment around the tumor, characterized by a dense tissue that inhibits blood vessel formation and blocks immune infiltration.
“Delivery MEDICINAL is a huge challenge due to the microenvironmental architecture of these difficult-to-treat tumors,” explains Prabhani Atukorale, assistant professor of biomedical engineering at UMass Amherst and one of the paper’s corresponding authors. She adds that this environment also blocks the activation of the body’s immune cells and their penetration into tumors.
Marcus Ruscetti, assistant professor of molecular, cellular and cancer biology at UMass, points out, “Pancreatic cancer, unfortunately, does not respond to most conventional therapies, such as chemotherapy or even immunotherapy, which has greatly revolutionized cancer therapy in the last 10 years“.
What does the new method of treating pancreatic cancer entail
Previous research has shown that the drugs trametinib and palbociclib can promote the development of blood vessels, facilitating the delivery of T cells and chemotherapy to tumors.
The proposed new method involves the use of the Stimulating Interferon Gene (STING) pathway and the TRL4 pathway.
“If we can trick the immune system into thinking there is a viral infection, then we exploit a very robust anti-tumor immune response to bring to tumor immunotherapy”, explains Prof. Atukorale.
Researchers use nanoparticles to deliver STING and TRL4 agonists, thereby providing an advantage in immune system activation. Specifically, agonists, which are any chemical substances that can trigger a biological response, are encapsulated in a novel lipid-based nanoparticle design.
Nanoparticles are highly effective in delivering agonists to the tumor microenvironment, solving the problem of combining agents that do not mix easily. Prof. Atukorale explains: “These nanoparticles ensure the simultaneous transport of agonists into the bloodstream and to the same target cell.”
Using lipid-based biocompatible materials, researchers are able to package drugs that work together but do not mix and effectively target the tumor.
The results of the study are promising: eight out of nine mice showed tumor necrosis and tumor shrinkage.
“We had two mice that had complete responses, meaning the tumors disappeared completely, which is quite promising. I have never seen anything like this in this model before”, says Prof. Ruscetti.
Although the tumors recurred after treatment was discontinued, the researchers believe this method represents an important step toward finding a cure for the condition.
The research paves the way for the development of treatments that may be applicable to other types of cancer, including colon, lung, liver and cholangiocarcinoma.
“We can tailor agonist rates, drug combinations, targeting molecules, but essentially keeping the same platform. This is what will hopefully make it translational, but also adjustable for each patient, because many of these cancer therapies must be personalized“, the researchers add.
